Cancers

13 pages, 948 KiB

Open AccessArticle

Real-World Outcomes of Nivolumab, Pembrolizumab, and Atezolizumab Treatment Efficacy in Korean Veterans with Stage IV Non-Small-Cell Lung Cancer

by Ahrong Ham, Young Lee, Hae Su Kim and Taekyu Lim

Cancers 2023, 15(16), 4198; https://doi.org/10.3390/cancers15164198 - 21 Aug 2023

Cited by 4 | Viewed by 2853

Abstract

Purpose: To provide a comprehensive analysis of ICI usage and treatment outcomes in elderly Korean veterans with stage IV NSCLC. Methods: Patients diagnosed with stage IV NSCLC between 2016 and 2021 were included, and three cohorts were derived according to the type of [...] Read more.

Purpose: To provide a comprehensive analysis of ICI usage and treatment outcomes in elderly Korean veterans with stage IV NSCLC. Methods: Patients diagnosed with stage IV NSCLC between 2016 and 2021 were included, and three cohorts were derived according to the type of ICI received. Thereafter, the clinical characteristics and survival outcomes were compared. Results: Of the 180 patients with NSCLC (median age, 76 years) included in this study, 49 (27.7%), 61 (33.9%), and 70 (38.9%) received pembrolizumab, nivolumab, and atezolizumab, respectively, and 19.4%, 36.1%, and 34.4% had PD-L1 expressions < 1%, 1–49%, and ≥50%, respectively. The pembrolizumab, nivolumab, and atezolizumab groups, the objective response rates (ORR), and the disease control rates (DCR) were 22.4%, 8.2%, and 4.3% (p = 0.004), and 59.2, 55.7%, and 30.0% (p = 0.001), respectively. However, no difference in the overall survival (OS) rate was noted among the groups (12.6 months vs. 8.4 months vs. 7.7 months, p = 0.334). Similarly, there was no treatment specific OS benefit with respect to the tumor PD-L1 expression status. Interestingly, multivariate analysis identified bone metastasis as a significant poor prognostic factor for OS (HR = 2.75 [95% CI, 1.31–5.76], p = 0.007). Conclusion: Pembrolizumab and nivolumab showed stronger associations with increases in ORR and DCR than atezolizumab, but no statistically significant differences were observed with respect to OS. Full article

(This article belongs to the Section Cancer Immunology and Immunotherapy)

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3 pages, 180 KiB

Open AccessEditorial

Advancing Cancer Immunotherapy: From Molecular Mechanisms to Clinical Applications

by Xianda Zhao, Timothy Starr and Subbaya Subramanian

Cancers 2023, 15(16), 4197; https://doi.org/10.3390/cancers15164197 - 21 Aug 2023

Cited by 1 | Viewed by 1981

Abstract

In recent years, cancer immunotherapy research has made remarkable progress, completely transforming the cancer treatment landscape [...] Full article

(This article belongs to the Special Issue Tumor Immunology and Immunotherapy Resistance)

9 pages, 1129 KiB

Open AccessArticle

Efficacy of Empirical Radioiodine Therapy in Patients with Differentiated Thyroid Cancer and Elevated Serum Thyroglobulin without Evidence of Structural Disease: A Propensity Score Analysis

by Leandra Piscopo, Emilia Zampella, Fabio Volpe, Valeria Gaudieri, Carmela Nappi, Paolo Cutillo, Federica Volpicelli, Maria Falzarano, Leonardo Pace, Alberto Cuocolo and Michele Klain

Cancers 2023, 15(16), 4196; https://doi.org/10.3390/cancers15164196 - 21 Aug 2023

Cited by 2 | Viewed by 1478

Abstract

We assessed the outcome of administration of empiric radioactive iodine (RAI) therapy to patients with differentiated thyroid cancer (DTC), in a propensity-score-matched cohort of patients with biochemical incomplete response (BIR) and without evidence of structural disease. We retrospectively evaluated 820 DTC patients without [...] Read more.

We assessed the outcome of administration of empiric radioactive iodine (RAI) therapy to patients with differentiated thyroid cancer (DTC), in a propensity-score-matched cohort of patients with biochemical incomplete response (BIR) and without evidence of structural disease. We retrospectively evaluated 820 DTC patients without distant metastases, who underwent total thyroidectomy followed by RAI therapy, with available BIR at 12 months and follow-up evaluations. The patients were categorized according to the administration of empiric therapy (ET). To account for differences between patients with (n = 119) and without (n = 701) ET, a propensity-score-matched cohort of 119 ET and 119 no-ET patients was created. The need for additional therapy and the occurrence of structural disease were considered as end-points. During a median follow-up of 53 months (range 3–285), 57 events occurred (24% cumulative event rate). The rate of events was significantly higher in the no-ET compared to the ET patients (30% vs. 18% p < 0.001). The multivariate Cox analysis identified age (p < 0.01), pre-therapy Tg (p < 0.05) and empiric RAI therapy (p < 0.01) as predictors of outcome. The Kaplan–Meier analysis found that progression-free survival was lower in no-ET patients compared to the ET group (p < 0.01). In patients with DTC treated with surgery and RAI, and with biochemical incomplete response at the 12-month evaluation, their prognosis seemed to be affected by Tg values and the empiric treatment. The identification of candidates for this approach may improve prognosis. Full article

(This article belongs to the Special Issue 2nd Edition: Advances in the Management of Thyroid Cancer)

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27 pages, 20717 KiB

Open AccessArticle

Relevance of ATM Status in Driving Sensitivity to DNA Damage Response Inhibitors in Patient-Derived Xenograft Models

by Ankur Karmokar, Rebecca Sargeant, Adina M. Hughes, Hana Baakza, Zena Wilson, Sara Talbot, Sarah Bloomfield, Elisabetta Leo, Gemma N. Jones, Maria Likhatcheva, Luis Tobalina, Emma Dean, Elaine B. Cadogan and Alan Lau

Cancers 2023, 15(16), 4195; https://doi.org/10.3390/cancers15164195 - 21 Aug 2023

Viewed by 1841

Abstract

Ataxia-telangiectasia mutated gene (ATM) is a key component of the DNA damage response (DDR) and double-strand break repair pathway. The functional loss of ATM (ATM deficiency) is hypothesised to enhance sensitivity to DDR inhibitors (DDRi). Whole-exome sequencing (WES), immunohistochemistry (IHC), and Western blotting [...] Read more.

Ataxia-telangiectasia mutated gene (ATM) is a key component of the DNA damage response (DDR) and double-strand break repair pathway. The functional loss of ATM (ATM deficiency) is hypothesised to enhance sensitivity to DDR inhibitors (DDRi). Whole-exome sequencing (WES), immunohistochemistry (IHC), and Western blotting (WB) were used to characterise the baseline ATM status across a panel of ATM mutated patient-derived xenograft (PDX) models from a range of tumour types. Antitumour efficacy was assessed with poly(ADP-ribose)polymerase (PARP, olaparib), ataxia- telangiectasia and rad3-related protein (ATR, AZD6738), and DNA-dependent protein kinase (DNA-PK, AZD7648) inhibitors as a monotherapy or in combination to associate responses with ATM status. Biallelic truncation/frameshift ATM mutations were linked to ATM protein loss while monoallelic or missense mutations, including the clinically relevant recurrent R3008H mutation, did not confer ATM protein loss by IHC. DDRi agents showed a mixed response across the PDX’s but with a general trend toward greater activity, particularly in combination in models with biallelic ATM mutation and protein loss. A PDX with an ATM splice-site mutation, 2127T > C, with a high relative baseline ATM expression and KAP1 phosphorylation responded to all DDRi treatments. These data highlight the heterogeneity and complexity in describing targetable ATM-deficiencies and the fact that current patient selection biomarker methods remain imperfect; although, complete ATM loss was best able to enrich for DDRi sensitivity. Full article

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21 pages, 4008 KiB

Open AccessReview

Nanotechnology-Based Drug Delivery Approaches of Mangiferin: Promises, Reality and Challenges in Cancer Chemotherapy

by Muhammad Sarfraz, Abida Khan, Gaber El-Saber Batiha, Muhammad Furqan Akhtar, Ammara Saleem, Basiru Olaitan Ajiboye, Mehnaz Kamal, Abuzer Ali, Nawaf M. Alotaibi, Shams Aaghaz, Muhammad Irfan Siddique and Mohd Imran

Cancers 2023, 15(16), 4194; https://doi.org/10.3390/cancers15164194 - 21 Aug 2023

Cited by 2 | Viewed by 2565

Abstract

Mangiferin (MGF), a xanthone derived from Mangifera indica L., initially employed as a nutraceutical, is now being explored extensively for its anticancer potential. Scientists across the globe have explored this bioactive for managing a variety of cancers using validated in vitro and in [...] Read more.

Mangiferin (MGF), a xanthone derived from Mangifera indica L., initially employed as a nutraceutical, is now being explored extensively for its anticancer potential. Scientists across the globe have explored this bioactive for managing a variety of cancers using validated in vitro and in vivo models. The in vitro anticancer potential of this biomolecule on well-established breast cancer cell lines such as MDA-MB-23, BEAS-2B cells and MCF-7 is closer to many approved synthetic anticancer agents. However, the solubility and bioavailability of this xanthone are the main challenges, and its oral bioavailability is reported to be less than 2%, and its aqueous solubility is also 0.111 mg/mL. Nano-drug delivery systems have attempted to deliver the drugs at the desired site at a desired rate in desired amounts. Many researchers have explored various nanotechnology-based approaches to provide effective and safe delivery of mangiferin for cancer therapy. Nanoparticles were used as carriers to encapsulate mangiferin, protecting it from degradation and facilitating its delivery to cancer cells. They have attempted to enhance the bioavailability, safety and efficacy of this very bioactive using drug delivery approaches. The present review focuses on the origin and structure elucidation of mangiferin and its derivatives and the benefits of this bioactive. The review also offers insight into the delivery-related challenges of mangiferin and its applications in nanosized forms against cancer. The use of a relatively new deep-learning approach to solve the pharmacokinetic issues of this bioactive has also been discussed. The review also critically analyzes the future hope for mangiferin as a therapeutic agent for cancer management. Full article

(This article belongs to the Topic Application of Nanomaterials and Nanobiotechnology in Cancer)

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27 pages, 41679 KiB

Open AccessArticle

A Novel Mouse Model of Combined Hepatocellular-Cholangiocarcinoma Induced by Diethylnitrosamine and Loss of Ppp2r5d

by Judit Domènech Omella, Emanuela E. Cortesi, Iris Verbinnen, Michiel Remmerie, Hanghang Wu, Francisco J. Cubero, Tania Roskams and Veerle Janssens

Cancers 2023, 15(16), 4193; https://doi.org/10.3390/cancers15164193 - 21 Aug 2023

Viewed by 2207

Abstract

Primary liver cancer (PLC) can be classified in hepatocellular (HCC), cholangiocarcinoma (CCA), and combined hepatocellular-cholangiocarcinoma (cHCC-CCA). The molecular mechanisms involved in PLC development and phenotype decision are still not well understood. Complete deletion of Ppp2r5d, encoding the B56δ subunit of Protein Phosphatase 2A [...] Read more.

Primary liver cancer (PLC) can be classified in hepatocellular (HCC), cholangiocarcinoma (CCA), and combined hepatocellular-cholangiocarcinoma (cHCC-CCA). The molecular mechanisms involved in PLC development and phenotype decision are still not well understood. Complete deletion of Ppp2r5d, encoding the B56δ subunit of Protein Phosphatase 2A (PP2A), results in spontaneous HCC development in mice via a c-MYC-dependent mechanism. In the present study, we aimed to examine the role of Ppp2r5d in an independent mouse model of diethylnitrosamine (DEN)-induced hepatocarcinogenesis. Ppp2r5d deletion (heterozygous and homozygous) accelerated HCC development, corroborating its tumor-suppressive function in liver and suggesting Ppp2r5d may be haploinsufficient. Ppp2r5d-deficient HCCs stained positively for c-MYC, consistent with increased AKT activation in pre-malignant and tumor tissues of Ppp2r5d-deficient mice. We also found increased YAP activation in Ppp2r5d-deficient tumors. Remarkably, in older mice, Ppp2r5d deletion resulted in cHCC-CCA development in this model, with the CCA component showing increased expression of progenitor markers (SOX9 and EpCAM). Finally, we observed an upregulation of Ppp2r5d in tumors from wildtype and heterozygous mice, revealing a tumor-specific control mechanism of Ppp2r5d expression, and suggestive of the involvement of Ppp2r5d in a negative feedback regulation restricting tumor growth. Our study highlights the tumor-suppressive role of mouse PP2A-B56δ in both HCC and cHCC-CCA, which may have important implications for human PLC development and targeted treatment. Full article

(This article belongs to the Collection Primary Liver Cancer)

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3 pages, 168 KiB

Open AccessEditorial

Peripheral T-Cell Lymphoma: From Biological Research to New Therapies

by Shingo Nakahata and Kazuhiro Morishita

Cancers 2023, 15(16), 4192; https://doi.org/10.3390/cancers15164192 - 21 Aug 2023

Cited by 1 | Viewed by 1237

Abstract

This series of six articles (four reviews and two original articles) is presented by international leaders on peripheral T-cell lymphomas (PTCL) [...] Full article

(This article belongs to the Special Issue Peripheral T-cell Lymphoma: From Biological Research to New Therapies)

16 pages, 8671 KiB

Open AccessArticle

Skin Extracellular Matrix Breakdown Following Paclitaxel Therapy in Patients with Chemotherapy-Induced Peripheral Neuropathy

by Nathan P. Staff, Sybil C. Hrstka, Surendra Dasari, Enrico Capobianco and Sandra Rieger

Cancers 2023, 15(16), 4191; https://doi.org/10.3390/cancers15164191 - 21 Aug 2023

Cited by 1 | Viewed by 2003

Abstract

The chemotherapeutic agent paclitaxel causes peripheral neuropathy, a dose-limiting side effect, in up to 68% of cancer patients. In this study, we investigated the impact of paclitaxel therapy on the skin of breast cancer patients with chemotherapy-induced peripheral neuropathy (CIPN), building upon previous [...] Read more.

The chemotherapeutic agent paclitaxel causes peripheral neuropathy, a dose-limiting side effect, in up to 68% of cancer patients. In this study, we investigated the impact of paclitaxel therapy on the skin of breast cancer patients with chemotherapy-induced peripheral neuropathy (CIPN), building upon previous findings in zebrafish and rodents. Comprehensive assessments, including neurological examinations and quality of life questionnaires, were conducted, followed by intraepidermal nerve fiber (IENF) density evaluations using skin punch biopsies. Additionally, RNA sequencing, immunostaining for Matrix-Metalloproteinase 13 (MMP-13), and transmission electron microscopy provided insights into molecular and ultrastructural changes in this skin. The results showed no significant difference in IENF density between the control and CIPN patients despite the presence of patient-reported CIPN symptoms. Nevertheless, the RNA sequencing and immunostaining on the skin revealed significantly upregulated MMP-13, which is known to play a key role in CIPN caused by paclitaxel therapy. Additionally, various genes involved in the regulation of the extracellular matrix, microtubules, cell cycle, and nervous system were significantly and differentially expressed. An ultrastructural examination of the skin showed changes in collagen and basement membrane structures. These findings highlight the presence of CIPN in the absence of IENF density changes and support the role of skin remodeling as a major contributor to CIPN. Full article

(This article belongs to the Special Issue Management of Side Effects of Cancer Treatments: New Approaches)

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12 pages, 507 KiB

Open AccessReview

Extended Adjuvant Endocrine Therapy in Early Breast Cancer Patients—Review and Perspectives

by Inga Bekes and Jens Huober

Cancers 2023, 15(16), 4190; https://doi.org/10.3390/cancers15164190 - 21 Aug 2023

Cited by 4 | Viewed by 2524

Abstract

Seventy percent of all breast cancer subtypes are hormone receptor-positive. Adjuvant endocrine therapy in these patients plays a key role. Despite the traditional duration of a 5-year intake, the risk of relapse remains elevated in a substantial proportion of patients. Several trials report [...] Read more.

Seventy percent of all breast cancer subtypes are hormone receptor-positive. Adjuvant endocrine therapy in these patients plays a key role. Despite the traditional duration of a 5-year intake, the risk of relapse remains elevated in a substantial proportion of patients. Several trials report that the risk of late recurrence is reduced by the extension of adjuvant endocrine therapy beyond 5 years. However, the optimal duration of endocrine therapy is still a matter of debate. The newer data only show a marginal benefit resulting from extension beyond 7 to 10 years. Furthermore, extension may be associated with more side effects. Thus, the adequate selection of patients qualifying for an extended adjuvant therapy is of importance. Tools/genomic tests, which include the characteristics of the patient and the tumor, may help to better identify patients with a risk of a late relapse. Taken together, the magnitude of benefit for extended adjuvant endocrine therapy is based on the precise estimation of the risk of relapse after 5 years. This must be balanced against the long-term side effects of endocrine treatment and the competing risks. For patients with an intermediate risk, 7 years appears to be the optimal duration, and in those with high-risk features, endocrine therapy up to 10 years may be considered. Full article

(This article belongs to the Special Issue State-of-the-Art and Perspectives in the Treatment of Hormone-Receptor-Positive Breast Cancer)

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19 pages, 6835 KiB

Open AccessArticle

Oncogenic Targets Regulated by Tumor-Suppressive miR-30c-1-3p and miR-30c-2-3p: TRIP13 Facilitates Cancer Cell Aggressiveness in Breast Cancer

by Reiko Mitsueda, Hiroko Toda, Yoshiaki Shinden, Kosuke Fukuda, Ryutaro Yasudome, Mayuko Kato, Naoko Kikkawa, Takao Ohtsuka, Akihiro Nakajo and Naohiko Seki

Cancers 2023, 15(16), 4189; https://doi.org/10.3390/cancers15164189 - 21 Aug 2023

Cited by 3 | Viewed by 1893

Abstract

Accumulating evidence suggests that the miR-30 family act as critical players (tumor-suppressor or oncogenic) in a wide range of human cancers. Analysis of microRNA (miRNA) expression signatures and The Cancer Genome Atlas (TCGA) database revealed that that two passenger strand miRNAs, miR-30c-1-3p and [...] Read more.

Accumulating evidence suggests that the miR-30 family act as critical players (tumor-suppressor or oncogenic) in a wide range of human cancers. Analysis of microRNA (miRNA) expression signatures and The Cancer Genome Atlas (TCGA) database revealed that that two passenger strand miRNAs, miR-30c-1-3p and miR-30c-2-3p, were downregulated in cancer tissues, and their low expression was closely associated with worse prognosis in patients with BrCa. Functional assays showed that miR-30c-1-3p and miR-30c-2-3p overexpression significantly inhibited cancer cell aggressiveness, suggesting these two miRNAs acted as tumor-suppressors in BrCa cells. Notably, involvement of passenger strands of miRNAs is a new concept of cancer research. Further analyses showed that seven genes (TRIP13, CCNB1, RAD51, PSPH, CENPN, KPNA2, and MXRA5) were putative targets of miR-30c-1-3p and miR-30c-2-3p in BrCa cells. Expression of seven genes were upregulated in BrCa tissues and predicted a worse prognosis of the patients. Among these genes, we focused on TRIP13 and investigated the functional significance of this gene in BrCa cells. Luciferase reporter assays showed that TRIP13 was directly regulated by these two miRNAs. TRIP13 knockdown using siRNA attenuated BrCa cell aggressiveness. Inactivation of TRIP13 using a specific inhibitor prevented the malignant transformation of BrCa cells. Exploring the molecular networks controlled by miRNAs, including passenger strands, will facilitate the identification of diagnostic markers and therapeutic target molecules in BrCa. Full article

(This article belongs to the Special Issue Breast Cancer: Novel Histological and Molecular Markers for Diagnosis, Prognosis, Therapeutic Prediction, and Drug Resistance)

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15 pages, 1548 KiB

Open AccessReview

Decoding the Complexity of Immune–Cancer Cell Interactions: Empowering the Future of Cancer Immunotherapy

by Kaitlyn Maffuid and Yanguang Cao

Cancers 2023, 15(16), 4188; https://doi.org/10.3390/cancers15164188 - 21 Aug 2023

Cited by 16 | Viewed by 3031

Abstract

The tumor and tumor microenvironment (TME) consist of a complex network of cells, including malignant, immune, fibroblast, and vascular cells, which communicate with each other. Disruptions in cell–cell communication within the TME, caused by a multitude of extrinsic and intrinsic factors, can contribute [...] Read more.

The tumor and tumor microenvironment (TME) consist of a complex network of cells, including malignant, immune, fibroblast, and vascular cells, which communicate with each other. Disruptions in cell–cell communication within the TME, caused by a multitude of extrinsic and intrinsic factors, can contribute to tumorigenesis, hinder the host immune system, and enable tumor evasion. Understanding and addressing intercellular miscommunications in the TME are vital for combating these processes. The effectiveness of immunotherapy and the heterogeneous response observed among patients can be attributed to the intricate cellular communication between immune cells and cancer cells. To unravel these interactions, various experimental, statistical, and computational techniques have been developed. These include ligand–receptor analysis, intercellular proximity labeling approaches, and imaging-based methods, which provide insights into the distorted cell–cell interactions within the TME. By characterizing these interactions, we can enhance the design of cancer immunotherapy strategies. In this review, we present recent advancements in the field of mapping intercellular communication, with a particular focus on immune–tumor cellular interactions. By modeling these interactions, we can identify critical factors and develop strategies to improve immunotherapy response and overcome treatment resistance. Full article

(This article belongs to the Special Issue Cell Therapy, Bispecific Antibodies and other Immunotherapies Against Cancer)

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26 pages, 1459 KiB

Open AccessReview

Clinical Significance of Non-Coding RNA Regulation of Programmed Cell Death in Hepatocellular Carcinoma

by Wuyu Chen, Minghao Ruan, Minghao Zou, Fuchen Liu and Hui Liu

Cancers 2023, 15(16), 4187; https://doi.org/10.3390/cancers15164187 - 21 Aug 2023

Cited by 4 | Viewed by 1502

Abstract

Hepatocellular carcinoma (HCC) is a widely prevalent and malignantly progressive tumor. Most patients are typically diagnosed with HCC at an advanced stage, posing significant challenges in the execution of curative surgical interventions. Non-coding RNAs (ncRNAs) represent a distinct category of RNA molecules not [...] Read more.

Hepatocellular carcinoma (HCC) is a widely prevalent and malignantly progressive tumor. Most patients are typically diagnosed with HCC at an advanced stage, posing significant challenges in the execution of curative surgical interventions. Non-coding RNAs (ncRNAs) represent a distinct category of RNA molecules not directly involved in protein synthesis. However, they possess the remarkable ability to regulate gene expression, thereby exerting significant regulatory control over cellular processes. Notably, ncRNAs have been implicated in the modulation of programmed cell death (PCD), a crucial mechanism that various therapeutic agents target in the fight against HCC. This review summarizes the clinical significance of ncRNA regulation of PCD in HCC, including patient diagnosis, prognosis, drug resistance, and side effects. The aim of this study is to provide new insights and directions for the diagnosis and drug treatment strategies of HCC. Full article

(This article belongs to the Special Issue Hallmark Properties and Behind-the-Scenes Role of Non-coding RNAs in Gastrointestinal Cancers’ Onset, Progression and Metastasis)

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31 pages, 7340 KiB

Open AccessReview

Circulating Biomarkers Associated with the Diagnosis and Prognosis of B-Cell Progenitor Acute Lymphoblastic Leukemia

by Claudia Daniela Álvarez-Zúñiga, Idalia Garza-Veloz, Jacqueline Martínez-Rendón, Misael Ureño-Segura, Iván Delgado-Enciso and Margarita L. Martinez-Fierro

Cancers 2023, 15(16), 4186; https://doi.org/10.3390/cancers15164186 - 20 Aug 2023

Cited by 1 | Viewed by 2801

Abstract

Acute lymphoblastic leukemia (ALL) is a hematological disease characterized by the dysfunction of the hematopoietic system that leads to arrest at a specific stage of stem cells development, suppressing the average production of cellular hematologic components. BCP-ALL is a neoplasm of the B-cell [...] Read more.

Acute lymphoblastic leukemia (ALL) is a hematological disease characterized by the dysfunction of the hematopoietic system that leads to arrest at a specific stage of stem cells development, suppressing the average production of cellular hematologic components. BCP-ALL is a neoplasm of the B-cell lineage progenitor. BCP-ALL is caused and perpetuated by several mechanisms that provide the disease with its tumor potential and genetic and cytological characteristics. These pathological features are used for diagnosis and the prognostication of BCP-ALL. However, most of these paraclinical tools can only be obtained by bone marrow aspiration, which, as it is an invasive study, can delay the diagnosis and follow-up of the disease, in addition to the anesthetic risk it entails for pediatric patients. For this reason, it is crucial to find noninvasive and accessible ways to supply information concerning diagnosis, prognosis, and the monitoring of the disease, such as circulating biomarkers. In oncology, a biomarker is any measurable indicator that demonstrates the presence of malignancy, tumoral behavior, prognosis, or responses to treatments. This review summarizes circulating molecules associated with BCP-ALL with potential diagnostic value, classificatory capacity during monitoring specific clinic features of the disease, and/or capacity to identify each BCP-ALL stage regarding its evolution and outcome of the patients with BCP-ALL. In the same way, we provide and classify biomarkers that may be used in further studies focused on clinical approaches or therapeutic target identification for BCP-ALL. Full article

(This article belongs to the Section Cancer Biomarkers)

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14 pages, 1209 KiB

Open AccessArticle

Application of 18F-PSMA-1007 PET/MR Imaging in Early Biochemical Recurrence of Prostate Cancer: Results of a Prospective Study of 60 Patients with Very Low PSA Levels ≤ 0.5 ng/mL

by Małgorzata Mojsak, Piotr Szumowski, Anna Amelian, Marcin Hladunski, Bożena Kubas, Janusz Myśliwiec, Jan Kochanowicz and Marcin Moniuszko

Cancers 2023, 15(16), 4185; https://doi.org/10.3390/cancers15164185 - 20 Aug 2023

Cited by 1 | Viewed by 1676

Abstract

The use of 18F-PSMA-1007 and the role of PET/MR in the diagnosis of prostate cancer are not conclusively confirmed. There are reports indicating the potential pros and cons of using 18F-PSMA-1007 as well as the PET/MR technique in prostate cancer recurrence, but they [...] Read more.

The use of 18F-PSMA-1007 and the role of PET/MR in the diagnosis of prostate cancer are not conclusively confirmed. There are reports indicating the potential pros and cons of using 18F-PSMA-1007 as well as the PET/MR technique in prostate cancer recurrence, but they are not yet included in the EAU guidelines. The aim of the study was to assess the effectiveness of 18F-PSMA-1007 PET/MR in detecting BCR lesions at very low PSA levels <0.5 ng/mL. Methods: Sixty patients with BCR after radical prostatectomy (RP) with PSA ranged 0.1–0.5 ng/mL were enrolled in a prospective study. All patients underwent simultaneous whole-body and pelvic 18F-PSMA-1007 PET/MR. The obtained results were verified by 12-month follow-up. Results: Fifty-three lesions were detected in 45 patients with 75% detection rate. The mean PSA value was 0.31 ng/mL. Of all PSMA-positive foci, 91% were localized in the pelvis, and only 9% of lesions were located in the extrapelvic region. Local recurrences were detected in 29%, PSMA-positive lymph nodes were detected in 64% of patients and bone metastases lesions were detected in 7% of patients. Conclusions: 18F-PSMA-1007 PET/MR seems to be an excellent diagnostic tool in patients with early BCR with very low PSA levels, especially with dt PSA < 6 months. The synergistic effect of combining 18F-PSMA-1007 and whole-body PET/MR with precise multiparametric assessment of pelvic lesions is of particular benefit in early BCR. Full article

(This article belongs to the Special Issue Prostate Cancer: Molecular Imaging and Magnetic Resonance Imaging (MRI))

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17 pages, 3286 KiB

Open AccessArticle

Circulating Tumour Cell Associated MicroRNA Profiles Change during Chemoradiation and Are Predictive of Response in Locally Advanced Rectal Cancer

by Stephanie H. Lim, Wei Chua, Weng Ng, Emilia Ip, Tania M. Marques, Nham T. Tran, Margarida Gama-Carvalho, Ray Asghari, Christopher Henderson, Yafeng Ma, Paul de Souza and Kevin J. Spring

Cancers 2023, 15(16), 4184; https://doi.org/10.3390/cancers15164184 - 20 Aug 2023

Cited by 1 | Viewed by 1539

Abstract

Locally advanced rectal cancer (LARC) has traditionally been treated with trimodality therapy consisting of neoadjuvant radiation +/− chemotherapy, surgery, and adjuvant chemotherapy. There is currently a clinical need for biomarkers to predict treatment response and outcomes, especially during neoadjuvant therapy. Liquid biopsies in [...] Read more.

Locally advanced rectal cancer (LARC) has traditionally been treated with trimodality therapy consisting of neoadjuvant radiation +/− chemotherapy, surgery, and adjuvant chemotherapy. There is currently a clinical need for biomarkers to predict treatment response and outcomes, especially during neoadjuvant therapy. Liquid biopsies in the form of circulating tumour cells (CTCs) and circulating nucleic acids in particular microRNAs (miRNA) are novel, the latter also being highly stable and clinically relevant regulators of disease. We studied a prospective cohort of 52 patients with LARC, and obtained samples at baseline, during treatment, and post-treatment. We enumerated CTCs during chemoradiation at these three time-points, using the Isoflux^TM (Fluxion Biosciences Inc., Alameda, CA, USA) CTC Isolation and detection platform. We then subjected the isolated CTCs to miRNA expression analyses, using a panel of 106 miRNA candidates. We identified CTCs in 73% of patients at baseline; numbers fell and miRNA expression profiles also changed during treatment. Between baseline and during treatment (week 3) time-points, three microRNAs (hsa-miR-95, hsa-miR-10a, and hsa-miR-16-1*) were highly differentially expressed. Importantly, hsa-miR-19b-3p and hsa-miR-483-5p were found to correlate with good response to treatment. The latter (hsa-miR-483-5p) was also found to be differentially expressed between good responders and poor responders. These miRNAs represent potential predictive biomarkers, and thus a potential miRNA-based treatment strategy. In this study, we demonstrate that CTCs are present and can be isolated in the non-metastatic early-stage cancer setting, and their associated miRNA profiles can potentially be utilized to predict treatment response. Full article

(This article belongs to the Special Issue Clinical Significance of cfRNAs as Tumor Biomarkers)

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21 pages, 3173 KiB

Open AccessArticle

Integrative Evaluation of the Clinical Significance Underlying Protein Arginine Methyltransferases in Hepatocellular Carcinoma

by Yikun Jiang, Shibo Wei, Jin-Mo Koo, Hea-Ju Kim, Wonyoung Park, Yan Zhang, He Guo, Ki-Tae Ha, Chang-Myung Oh, Jong-Sun Kang, Jee-Heon Jeong, Dongryeol Ryu, Kyeong-Jin Kim and Yunju Jo

Cancers 2023, 15(16), 4183; https://doi.org/10.3390/cancers15164183 - 20 Aug 2023

Cited by 3 | Viewed by 1705

Abstract

HCC is a major contributor to cancer-related mortality worldwide. Curative treatments are available for a minority of patients diagnosed at early stages; however, only a few multikinase inhibitors are available and are marginally effective in advanced cases, highlighting the need for novel therapeutic [...] Read more.

HCC is a major contributor to cancer-related mortality worldwide. Curative treatments are available for a minority of patients diagnosed at early stages; however, only a few multikinase inhibitors are available and are marginally effective in advanced cases, highlighting the need for novel therapeutic targets. One potential target is the protein arginine methyltransferase, which catalyzes various forms of arginine methylation and is often overexpressed in various cancers. However, the diverse expression patterns and clinical values of PRMTs in HCC remain unclear. In the present study, we evaluated the transcriptional expression of PRMTs in HCC cohorts using publicly available datasets. Our results revealed a significant association between PRMTs and prognosis in HCC patients with diverse clinical characteristics and backgrounds. This highlights the promising potential of PRMTs as prognostic biomarkers in patients with HCC. In particular, single-cell RNA (scRNA) sequencing analysis coupled with another human cohort study highlighted the pivotal role of PRMT1 in HCC progression, particularly in the context of Tex. Translating these findings into specific therapeutic decisions may address the unmet therapeutic needs of patients with HCC. Full article

(This article belongs to the Special Issue Prognostic and Predictive Biomarkers in Hepatocellular Carcinoma)

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16 pages, 2133 KiB

Open AccessArticle

Validation Study of the PALCOM Scale of Complexity of Palliative Care Needs: A Cohort Study in Advanced Cancer Patients

by Margarita Viladot, Jose-Luís Gallardo-Martínez, Fany Hernandez-Rodríguez, Jessica Izcara-Cobo, Josep Majó-LLopart, Marta Peguera-Carré, Giselle Russinyol-Fonte, Katia Saavedra-Cruz, Carmen Barrera, Manoli Chicote, Tanny-Daniela Barreto, Gemma Carrera, Jackeline Cimerman, Elena Font, Ignacio Grafia, Lucia Llavata, Javier Marco-Hernandez, Joan Padrosa, Anais Pascual, Dolors Quera, Carles Zamora-Martínez, Ana-Maria Bozzone, Carme Font and Albert Tuca Show full author list Hide full author list

Cancers 2023, 15(16), 4182; https://doi.org/10.3390/cancers15164182 - 20 Aug 2023

Cited by 1 | Viewed by 2080

Abstract

Background: In a patient-centred model of care, referral to early palliative care (EPC) depends on both the prognosis and the complexity of care needs. The PALCOM scale is a 5-domain multidimensional assessment tool developed to identify the level of complexity of palliative care [...] Read more.

Background: In a patient-centred model of care, referral to early palliative care (EPC) depends on both the prognosis and the complexity of care needs. The PALCOM scale is a 5-domain multidimensional assessment tool developed to identify the level of complexity of palliative care needs of cancer patients. The aim of this study was to validate the PALCOM scale. Patient and methods: We conducted a prospective cohort study of cancer patients to compare the PALCOM scale and expert empirical assessment (EA) of the complexity of palliative care needs. The EA had to categorise patients according to their complexity, considering that medium to high levels required priority attention from specialist EPC teams, while those with low levels could be managed by non-specialist teams. Systematically collected multidimensional variables were recorded in an electronic report form and stratified by level of complexity and rating system (PALCOM scale versus EA). The correlation rank (Kendall’s tau test) and accuracy test (F1-score) between the two rating systems were analysed. ROC curve analysis was used to determine the predictive power of the PALCOM scale. Results: A total of 283 advanced cancer patients were included. There were no significant differences in the frequency of the levels of complexity between the EA and the PALCOM scale (low 22.3–23.7%; medium 57.2–59.0%; high 20.5–17.3%). The prevalence of high symptom burden, severe pain, functional impairment, socio-familial risk, existential/spiritual problems, 6-month mortality and in-hospital death was significantly higher (p < 0.001) at the high complexity levels in both scoring systems. Comparative analysis showed a high correlation rank and accuracy between the two scoring systems (Kendall’s tau test 0.81, F1 score 0.84). The predictive ability of the PALCOM scale was confirmed by an area under the curve in the ROC analysis of 0.907 for high and 0.902 for low complexity. Conclusions: In a patient-centred care model, the identification of complexity is a key point to appropriate referral and management of shared care with EPC teams. The PALCOM scale is a high precision tool for determining the level of complexity of palliative care needs. Full article

(This article belongs to the Special Issue Integrating Palliative Care in Oncology)

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26 pages, 1942 KiB

Open AccessReview

Exploiting Long Non-Coding RNAs and Circular RNAs as Pharmacological Targets in Triple-Negative Breast Cancer Treatment

by Alina Catalina Palcau, Renata Brandi, Nikolay Hristov Mehterov, Claudio Botti, Giovanni Blandino and Claudio Pulito

Cancers 2023, 15(16), 4181; https://doi.org/10.3390/cancers15164181 - 20 Aug 2023

Cited by 4 | Viewed by 1954

Abstract

Breast cancer is one of the most frequent causes of cancer death among women worldwide. In particular, triple-negative breast cancer (TNBC) represents the most aggressive breast cancer subtype because it is characterized by the absence of molecular targets, thus making it an orphan [...] Read more.

Breast cancer is one of the most frequent causes of cancer death among women worldwide. In particular, triple-negative breast cancer (TNBC) represents the most aggressive breast cancer subtype because it is characterized by the absence of molecular targets, thus making it an orphan type of malignancy. The discovery of new molecular druggable targets is mandatory to improve treatment success. In that context, non-coding RNAs represent an opportunity for modulation of cancer. They are RNA molecules with apparently no protein coding potential, which have been already demonstrated to play pivotal roles within cells, being involved in different processes, such as proliferation, cell cycle regulation, apoptosis, migration, and diseases, including cancer. Accordingly, they could be used as targets for future TNBC personalized therapy. Moreover, the peculiar characteristics of non-coding RNAs make them reliable biomarkers to monitor cancer treatment, thus, to monitor recurrence or chemoresistance, which are the most challenging aspects in TNBC. In the present review, we focused on the oncogenic or oncosuppressor role of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) mostly involved in TNBC, highlighting their mode of action and depicting their potential role as a biomarker and/or as targets of new non-coding RNA-based therapeutics. Full article

(This article belongs to the Special Issue The Role of Long Non-coding RNA in Solid Tumors)

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10 pages, 243 KiB

Open AccessArticle

Easily Applicable Predictive Score for Differential Diagnosis of Prefibrotic Primary Myelofibrosis from Essential Thrombocythemia

by Danijela Lekovic, Andrija Bogdanovic, Marta Sobas, Isidora Arsenovic, Mihailo Smiljanic, Jelena Ivanovic, Jelena Bodrozic, Vladan Cokic and Natasa Milic

Cancers 2023, 15(16), 4180; https://doi.org/10.3390/cancers15164180 - 20 Aug 2023

Cited by 3 | Viewed by 1935

Abstract

Essential thrombocythemia (ET) and prefibrotic primary myelofibrosis (prePMF) initially have a similar phenotypic presentation with thrombocytosis. The aim of our study was to determine significant clinical-laboratory parameters at presentation to differentiate prePMF from ET as well as to develop and validate a predictive [...] Read more.

Essential thrombocythemia (ET) and prefibrotic primary myelofibrosis (prePMF) initially have a similar phenotypic presentation with thrombocytosis. The aim of our study was to determine significant clinical-laboratory parameters at presentation to differentiate prePMF from ET as well as to develop and validate a predictive diagnostic prePMF model. This retrospective study included 464 patients divided into ET (289 pts) and prePMF (175 pts) groups. The model was built using data from a development cohort (229 pts; 143 ET, 86 prePMF), which was then tested in an internal validation cohort (235 pts; 146 ET, 89 prePMF). The most important prePMF predictors in the multivariate logistic model were age ≥ 60 years (RR = 2.2), splenomegaly (RR = 13.2), and increased lactat-dehidrogenase (RR = 2.8). Risk scores were assigned according to derived relative risk (RR) for age ≥ 60 years (1 point), splenomegaly (2 points), and increased lactat-dehidrogenase (1 point). Positive predictive value (PPV) for pre-PMF diagnosis with a score of ≥points was 69.8%, while for a score of ≥3 it was 88.2%. Diagnostic performance had similar values in the validation cohort. In MPN patients with thrombocytosis at presentation, the application of the new model enables differentiation of pre-PMF from ET, which is clinically relevant considering that these diseases have different prognoses and treatments. Full article

16 pages, 2512 KiB

Open AccessReview

The Role of GAB1 in Cancer

by Manuel Jesús Pérez-Baena, Francisco Josué Cordero-Pérez, Jesús Pérez-Losada and Marina Holgado-Madruga

Cancers 2023, 15(16), 4179; https://doi.org/10.3390/cancers15164179 - 20 Aug 2023

Cited by 3 | Viewed by 2712

Abstract

GRB2-associated binder 1 (GAB1) is the inaugural member of the GAB/DOS family of pleckstrin homology (PH) domain-containing proteins. Upon receiving various stimuli, GAB1 transitions from the cytoplasm to the membrane where it is phosphorylated by a range of kinases. This event recruits SH2 [...] Read more.

GRB2-associated binder 1 (GAB1) is the inaugural member of the GAB/DOS family of pleckstrin homology (PH) domain-containing proteins. Upon receiving various stimuli, GAB1 transitions from the cytoplasm to the membrane where it is phosphorylated by a range of kinases. This event recruits SH2 domain-containing proteins like SHP2, PI3K’s p85 subunit, CRK, and others, thereby activating distinct signaling pathways, including MAPK, PI3K/AKT, and JNK. GAB1-deficient embryos succumb in utero, presenting with developmental abnormalities in the heart, placenta, liver, skin, limb, and diaphragm myocytes. Oncogenic mutations have been identified in the context of cancer. GAB1 expression levels are disrupted in various tumors, and elevated levels in patients often portend a worse prognosis in multiple cancer types. This review focuses on GAB1’s influence on cellular transformation particularly in proliferation, evasion of apoptosis, metastasis, and angiogenesis—each of these processes being a cancer hallmark. GAB1 also modulates the resistance/sensitivity to antitumor therapies, making it a promising target for future anticancer strategies. Full article

(This article belongs to the Special Issue Advances in Cancer Therapeutics)

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22 pages, 1198 KiB

Open AccessReview

Oncolytic Viruses and Immune Checkpoint Inhibitors: The “Hot” New Power Couple

by Charlotte Lovatt and Alan L. Parker

Cancers 2023, 15(16), 4178; https://doi.org/10.3390/cancers15164178 - 19 Aug 2023

Cited by 11 | Viewed by 3505

Abstract

Immune checkpoint inhibitors (ICIs) have revolutionized cancer care and shown remarkable efficacy clinically. This efficacy is, however, limited to subsets of patients with significant infiltration of lymphocytes into the tumour microenvironment. To extend their efficacy to patients who fail to respond or achieve [...] Read more.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer care and shown remarkable efficacy clinically. This efficacy is, however, limited to subsets of patients with significant infiltration of lymphocytes into the tumour microenvironment. To extend their efficacy to patients who fail to respond or achieve durable responses, it is now becoming evident that complex combinations of immunomodulatory agents may be required to extend efficacy to patients with immunologically “cold” tumours. Oncolytic viruses (OVs) have the capacity to selectively replicate within and kill tumour cells, resulting in the induction of immunogenic cell death and the augmentation of anti-tumour immunity, and have emerged as a promising modality for combination therapy to overcome the limitations seen with ICIs. Pre-clinical and clinical data have demonstrated that OVs can increase immune cell infiltration into the tumour and induce anti-tumour immunity, thus changing a “cold” tumour microenvironment that is commonly associated with poor response to ICIs, to a “hot” microenvironment which can render patients more susceptible to ICIs. Here, we review the major viral vector platforms used in OV clinical trials, their success when used as a monotherapy and when combined with adjuvant ICIs, as well as pre-clinical studies looking at the effectiveness of encoding OVs to deliver ICIs locally to the tumour microenvironment through transgene expression. Full article

(This article belongs to the Collection Advances and Future Prospects in Oncolytic Virus Immunotherapy)

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11 pages, 1827 KiB

Open AccessArticle

Comparison of Long-Term Oncological Results in Young Women with Breast Cancer between BRCA-Mutation Carriers Versus Non-Carriers: How Tumor and Genetic Risk Factors Influence the Clinical Prognosis

by Corrado Tinterri, Simone Di Maria Grimaldi, Andrea Sagona, Erika Barbieri, Shadya Darwish, Alberto Bottini, Giuseppe Canavese and Damiano Gentile

Cancers 2023, 15(16), 4177; https://doi.org/10.3390/cancers15164177 - 19 Aug 2023

Cited by 9 | Viewed by 1437

Abstract

Background: Breast cancer (BC) is very uncommon in young women (YW) and it is unclear whether a BRCA mutation has prognostic implications. Our aim was to evaluate the characteristics of YW with BC by comparing the long-term oncological results between BRCA-mutation carriers and [...] Read more.

Background: Breast cancer (BC) is very uncommon in young women (YW) and it is unclear whether a BRCA mutation has prognostic implications. Our aim was to evaluate the characteristics of YW with BC by comparing the long-term oncological results between BRCA-mutation carriers and non-carriers. Methods: We retrospectively reviewed all the consecutive YW (aged 18–40 years) diagnosed with BC. Endpoints were disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS). Results: 63 YW with a BRCA mutation were compared with 339 YW without BRCA mutation. BRCA-mutation carriers were younger (60.3% versus 34.8% if age ≤ 35 years, p = 0.001) and presented with more aggressive tumors (66.7% versus 40.7% if G3, p = 0.001; 57.2% versus 12.4% if biological subtype triple-negative, p = 0.001; 73.0% versus 39.2% if Ki67 ≥ 25%, p = 0.001). Non-carriers presented significantly better DFS, DDFS, and OS compared with BRCA-mutation carriers. Neoadjuvant chemotherapy was found to be an independent protective factor for OS in BRCA-mutation carriers. Conclusions: BC is more likely to present at a younger age (≤ 35 years) and with more aggressive characteristics (G3, triple-negative, Ki67 ≥ 25%) in YW with BRCA mutation compared with their non-mutated counterparts. Young BRCA-mutation carriers showed a poorer prognosis in terms of recurrence and survival compared with non-carriers. The implementation of neoadjuvant chemotherapy may improve survival in YW with BC and BRCA mutation. Full article

(This article belongs to the Special Issue Changing Landscape of Hereditary Breast and Ovarian Cancer 2.0)

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15 pages, 466 KiB

Open AccessReview

Immunotherapy in Melanoma: Recent Advancements and Future Directions

by Meghan J. Mooradian and Ryan J. Sullivan

Cancers 2023, 15(16), 4176; https://doi.org/10.3390/cancers15164176 - 19 Aug 2023

Cited by 4 | Viewed by 2453

Abstract

Immune checkpoint inhibition has fundamentally altered the treatment paradigm of resectable and unresectable melanoma, resulting in dramatic improvements in patient outcomes. With these advances, the five-year overall survival in patients with newly diagnosed unresectable disease has eclipsed 50%. Ongoing research is focused on [...] Read more.

Immune checkpoint inhibition has fundamentally altered the treatment paradigm of resectable and unresectable melanoma, resulting in dramatic improvements in patient outcomes. With these advances, the five-year overall survival in patients with newly diagnosed unresectable disease has eclipsed 50%. Ongoing research is focused on improving outcomes further, with a considerable emphasis on preventing de novo and acquired resistance and personalizing therapeutic options. Here, we review the ongoing advancements in the treatment of malignant melanoma, focusing on novel combination strategies that aim to build upon the successes of the last decade. Full article

(This article belongs to the Special Issue Immunotherapy in Melanoma: Recent Advances and Future Directions)

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23 pages, 3172 KiB

Open AccessReview

Role of Advanced Gastrointestinal Endoscopy in the Comprehensive Management of Neuroendocrine Neoplasms

by Harishankar Gopakumar, Vinay Jahagirdar, Jagadish Koyi, Dushyant Singh Dahiya, Hemant Goyal, Neil R. Sharma and Abhilash Perisetti

Cancers 2023, 15(16), 4175; https://doi.org/10.3390/cancers15164175 - 19 Aug 2023

Cited by 2 | Viewed by 2469

Abstract

Neuroendocrine neoplasms (NENs), also called neuroendocrine tumors (NETs), are relatively uncommon, heterogenous tumors primarily originating in the gastrointestinal tract. With the improvement in technology and increasing use of cross-sectional imaging and endoscopy, they are being discovered with increasing frequency. Although traditionally considered indolent [...] Read more.

Neuroendocrine neoplasms (NENs), also called neuroendocrine tumors (NETs), are relatively uncommon, heterogenous tumors primarily originating in the gastrointestinal tract. With the improvement in technology and increasing use of cross-sectional imaging and endoscopy, they are being discovered with increasing frequency. Although traditionally considered indolent tumors with good prognoses, some NENs exhibit aggressive behavior. Timely diagnosis, risk stratification, and management can often be a challenge. In general, small NENs without local invasion or lymphovascular involvement can often be managed using minimally invasive advanced endoscopic techniques, while larger lesions and those with evidence of lymphovascular invasion require surgery, systemic therapy, or a combination thereof. Ideal management requires a comprehensive and accurate understanding of the stage and grade of the tumor. With the recent advancements, a therapeutic advanced endoscopist can play a pivotal role in diagnosing, staging, and managing this rare condition. High-definition white light imaging and digital image enhancing technologies like narrow band imaging (NBI) in the newer endoscopes have improved the diagnostic accuracy of traditional endoscopy. The refinement of endoscopic ultrasound (EUS) over the past decade has revolutionized the role of endoscopy in diagnosing and managing various pathologies, including NENs. In addition to EUS-directed diagnostic biopsies, it also offers the ability to precisely assess the depth of invasion and lymphovascular involvement and thus stage NENs accurately. EUS-directed locoregional ablative therapies are increasingly recognized as highly effective, minimally invasive treatment modalities for NENs, particularly pancreatic NENs. Advanced endoscopic resection techniques like endoscopic submucosal dissection (ESD), endoscopic submucosal resection (EMR), and endoscopic full-thickness resection (EFTR) have been increasingly used over the past decade with excellent results in achieving curative resection of various early-stage gastrointestinal luminal lesions including NENs. In this article, we aim to delineate NENs of the different segments of the gastrointestinal (GI) tract (esophagus, gastric, pancreatic, and small and large intestine) and their management with emphasis on the endoscopic management of these tumors. Full article

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20 pages, 387 KiB

Open AccessReview

Surgical Considerations for Neoadjuvant Therapy for Pancreatic Adenocarcinoma

by Anish J. Jain, Jessica E. Maxwell, Matthew H. G. Katz and Rebecca A. Snyder

Cancers 2023, 15(16), 4174; https://doi.org/10.3390/cancers15164174 - 19 Aug 2023

Cited by 8 | Viewed by 2334

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a challenging disease process with a 5-year survival rate of only 11%. Neoadjuvant therapy in patients with localized pancreatic cancer has multiple theoretical benefits, including improved patient selection for surgery, early delivery of systemic therapy, and assessment of [...] Read more.

Pancreatic ductal adenocarcinoma (PDAC) is a challenging disease process with a 5-year survival rate of only 11%. Neoadjuvant therapy in patients with localized pancreatic cancer has multiple theoretical benefits, including improved patient selection for surgery, early delivery of systemic therapy, and assessment of response to therapy. Herein, we review key surgical considerations when selecting patients for neoadjuvant therapy and curative-intent resection. Accurate determination of resectability at diagnosis is critical and should be based on not only anatomic criteria but also biologic and clinical criteria to determine optimal treatment sequencing. Borderline resectable or locally advanced pancreatic cancer is best treated with neoadjuvant therapy and resection, including vascular resection and reconstruction when appropriate. Lastly, providing nutritional, prehabilitation, and supportive care interventions to improve patient fitness prior to surgical intervention and adequately address the adverse effects of therapy is critical. Full article

(This article belongs to the Special Issue Neoadjuvant Therapies in Pancreatic Cancer)

16 pages, 1187 KiB

Open AccessReview

Small Molecules against Metastatic Tumors: Concrete Perspectives and Shattered Dreams

by Massimo Serra, Davide Rubes, Sergio Schinelli and Mayra Paolillo

Cancers 2023, 15(16), 4173; https://doi.org/10.3390/cancers15164173 - 18 Aug 2023

Cited by 3 | Viewed by 1597

Abstract

Metastasis is the main cause of anti-cancer therapy failure, leading to unfavorable prognosis for patients. The true challenge to increase cancer patient life expectancy by making cancer a chronic disease with periodic but manageable relapses relies on the development of efficient therapeutic strategies [...] Read more.

Metastasis is the main cause of anti-cancer therapy failure, leading to unfavorable prognosis for patients. The true challenge to increase cancer patient life expectancy by making cancer a chronic disease with periodic but manageable relapses relies on the development of efficient therapeutic strategies specifically directed against key targets in the metastatic process. Traditional chemotherapy with classical alkylating agents, microtubule inhibitors, and antimetabolites has demonstrated its limited efficacy against metastatic cells due to their capacity to select chemo-resistant cell populations that undergo epithelial-to-mesenchymal transition (EMT), thus promoting the colonization of distant sites that, in turn, sustain the initial metastatic process. This scenario has prompted efforts aimed at discovering a wide variety of small molecules and biologics as potential anti-metastatic drugs directed against more specific targets known to be involved in the various stages of metastasis. In this short review, we give an overview of the most recent advances related to important families of antimetastatic small molecules: intracellular tyrosine kinase inhibitors, cyclin-dependent kinase inhibitors, KRAS inhibitors, and integrin antagonists. Although the majority of these small molecules are not yet approved and not available in the drug market, any information related to their stage of development could represent a precious and valuable tool to identify new targets in the endless fight against metastasis. Full article

(This article belongs to the Special Issue Development of Small Molecule Inhibitors for Metastatic Cancer)

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29 pages, 4688 KiB

Open AccessEditor’s ChoiceArticle

Brain Tumor Detection Based on Deep Learning Approaches and Magnetic Resonance Imaging

by Akmalbek Bobomirzaevich Abdusalomov, Mukhriddin Mukhiddinov and Taeg Keun Whangbo

Cancers 2023, 15(16), 4172; https://doi.org/10.3390/cancers15164172 - 18 Aug 2023

Cited by 69 | Viewed by 8931

Abstract

The rapid development of abnormal brain cells that characterizes a brain tumor is a major health risk for adults since it can cause severe impairment of organ function and even death. These tumors come in a wide variety of sizes, textures, and locations. [...] Read more.

The rapid development of abnormal brain cells that characterizes a brain tumor is a major health risk for adults since it can cause severe impairment of organ function and even death. These tumors come in a wide variety of sizes, textures, and locations. When trying to locate cancerous tumors, magnetic resonance imaging (MRI) is a crucial tool. However, detecting brain tumors manually is a difficult and time-consuming activity that might lead to inaccuracies. In order to solve this, we provide a refined You Only Look Once version 7 (YOLOv7) model for the accurate detection of meningioma, glioma, and pituitary gland tumors within an improved detection of brain tumors system. The visual representation of the MRI scans is enhanced by the use of image enhancement methods that apply different filters to the original pictures. To further improve the training of our proposed model, we apply data augmentation techniques to the openly accessible brain tumor dataset. The curated data include a wide variety of cases, such as 2548 images of gliomas, 2658 images of pituitary, 2582 images of meningioma, and 2500 images of non-tumors. We included the Convolutional Block Attention Module (CBAM) attention mechanism into YOLOv7 to further enhance its feature extraction capabilities, allowing for better emphasis on salient regions linked with brain malignancies. To further improve the model’s sensitivity, we have added a Spatial Pyramid Pooling Fast+ (SPPF+) layer to the network’s core infrastructure. YOLOv7 now includes decoupled heads, which allow it to efficiently glean useful insights from a wide variety of data. In addition, a Bi-directional Feature Pyramid Network (BiFPN) is used to speed up multi-scale feature fusion and to better collect features associated with tumors. The outcomes verify the efficiency of our suggested method, which achieves a higher overall accuracy in tumor detection than previous state-of-the-art models. As a result, this framework has a lot of potential as a helpful decision-making tool for experts in the field of diagnosing brain tumors. Full article

(This article belongs to the Special Issue Brain Tumor: Recent Advances and Challenges)

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21 pages, 1328 KiB

Open AccessReview

Risk-Stratified Therapy for Pediatric Acute Myeloid Leukemia

by Daisuke Tomizawa and Shin-Ichi Tsujimoto

Cancers 2023, 15(16), 4171; https://doi.org/10.3390/cancers15164171 - 18 Aug 2023

Cited by 6 | Viewed by 2725

Abstract

Acute Myeloid Leukemia (AML) is the second most common type of leukemia in children. Recent advances in high-resolution genomic profiling techniques have uncovered the mutational landscape of pediatric AML as distinct from adult AML. Overall survival rates of children with AML have dramatically [...] Read more.

Acute Myeloid Leukemia (AML) is the second most common type of leukemia in children. Recent advances in high-resolution genomic profiling techniques have uncovered the mutational landscape of pediatric AML as distinct from adult AML. Overall survival rates of children with AML have dramatically improved in the past 40 years, currently reaching 70% to 80% in developed countries. This was accomplished by the intensification of conventional chemotherapy, improvement in risk stratification using leukemia-specific cytogenetics/molecular genetics and measurable residual disease, appropriate use of allogeneic hematopoietic stem cell transplantation, and improvement in supportive care. However, the principle therapeutic approach for pediatric AML has not changed substantially for decades and improvement in event-free survival is rather modest. Further refinements in risk stratification and the introduction of emerging novel therapies to contemporary therapy, through international collaboration, would be key solutions for further improvements in outcomes. Full article

(This article belongs to the Special Issue Updates on Management and Clinical Trials in Pediatric Oncology)

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16 pages, 1992 KiB

Open AccessArticle

Obstetric Results after Fertility-Sparing Management of Non-Epithelial Ovarian Cancer

by Szymon Piątek, Iwona Szymusik, Piotr Sobiczewski, Wojciech Michalski, Magdalena Kowalska, Mariusz Ołtarzewski and Mariusz Bidziński

Cancers 2023, 15(16), 4170; https://doi.org/10.3390/cancers15164170 - 18 Aug 2023

Viewed by 1273

Abstract

Purpose: To assess the recurrence and birth rates among patients with non-epithelial ovarian cancer. Methods: The study included 146 patients with germ cell (GCT, n = 84) and sex cord-stromal tumors (SCST, n = 62), who underwent fertility-sparing surgery. Adjuvant chemotherapy was administered [...] Read more.

Purpose: To assess the recurrence and birth rates among patients with non-epithelial ovarian cancer. Methods: The study included 146 patients with germ cell (GCT, n = 84) and sex cord-stromal tumors (SCST, n = 62), who underwent fertility-sparing surgery. Adjuvant chemotherapy was administered to 86 (58.9%) patients. Most cases (133 out of 146) were staged FIGO I. Results: The 5- and 10-year disease-free survival rates were 91% and 83%, respectively. The recurrence risk was not associated with tumor histology, stage or age. Twenty-four months after the treatment, the rate of recurrence was higher than the rate of childbearing. The childbearing rates kept rising after the treatment and exceeded the rate of recurrence after 2 years. The cumulative incidence rates of birth 36, 60 and 120 months after treatment were 13.24%, 20.75%, and 42.37%, respectively. Chemotherapy was not related to childbearing. The patients’ age was related to the chance of childbearing. Conclusions: The prognoses of GCT and SCST are similar. Close follow-ups along with contraception should be offered to women during the first two years after treatment due to the increased risk of recurrence. After this period, relapses are rare and women can safely become pregnant. Full article

(This article belongs to the Special Issue Fertility and Pregnancy in Cancer Patients: Illusion or Reality)

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15 pages, 3357 KiB

Open AccessArticle

Improved Characterization of Circulating Tumor Cells and Cancer-Associated Fibroblasts in One-Tube Assay in Breast Cancer Patients Using Imaging Flow Cytometry

by Anna Muchlińska, Robert Wenta, Wiktoria Ścińska, Aleksandra Markiewicz, Grażyna Suchodolska, Elżbieta Senkus, Anna J. Żaczek and Natalia Bednarz-Knoll

Cancers 2023, 15(16), 4169; https://doi.org/10.3390/cancers15164169 - 18 Aug 2023

Cited by 2 | Viewed by 2115

Abstract

Circulating tumor cells (CTCs) and circulating cancer-associated fibroblasts (cCAFs) have been individually considered strong indicators of cancer progression. However, technical limitations have prevented their simultaneous analysis in the context of CTC phenotypes different from epithelial. This study aimed to analyze CTCs and cCAFs [...] Read more.

Circulating tumor cells (CTCs) and circulating cancer-associated fibroblasts (cCAFs) have been individually considered strong indicators of cancer progression. However, technical limitations have prevented their simultaneous analysis in the context of CTC phenotypes different from epithelial. This study aimed to analyze CTCs and cCAFs simultaneously in the peripheral blood of 210 breast cancer patients using DAPI/pan-keratin (K)/vimentin (V)/alpha-SMA/CD29/CD45/CD31 immunofluorescent staining and novel technology—imaging flow cytometry (imFC). Single and clustered CTCs of different sizes and phenotypes (i.e., epithelial phenotype K+/V− and epithelial–mesenchymal transition (EMT)-related CTCs, such as K+/V+, K−/V+, and K−/V−) were detected in 27.6% of the samples and correlated with metastases. EMT-related CTCs interacted more frequently with normal cells and tended to occur in patients with tumors progressing during therapy, while cCAFs coincided with CTCs (mainly K+/V− and K−/V−) in seven (3.3%) patients and seemed to correlate with the presence of metastases, particularly visceral ones. This study emphasizes the advantages of imFC in the field of liquid biopsy and highlights the importance of multimarker-based analysis of different subpopulations and phenotypes of cancer progression-related cells, i.e., CTCs and cCAFs. The co-detection of CTCs and cCAFs might improve the identification of patients at higher risk of progression and their monitoring during therapy. Full article

(This article belongs to the Special Issue Liquid Biopsy in Breast Cancer)

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