International Journal of Molecular Sciences

Editorial

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4 pages, 196 KiB

Open AccessEditorial

New Prognostic and Predictive Markers in Cancer Progression

by Susan Costantini and Alfredo Budillon

Int. J. Mol. Sci. 2020, 21(22), 8667; https://doi.org/10.3390/ijms21228667 - 17 Nov 2020

Cited by 8 | Viewed by 1715

Abstract

Biomarkers are a critical medical need for oncologists to predict and detect disease and to determine the best course of action for cancer patient care [...] Full article

(This article belongs to the Special Issue New Prognostic and Predictive Markers in Cancer Progression)

Research

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22 pages, 4568 KiB

Open AccessArticle

NLRP3 as Putative Marker of Ipilimumab-Induced Cardiotoxicity in the Presence of Hyperglycemia in Estrogen-Responsive and Triple-Negative Breast Cancer Cells

by Vincenzo Quagliariello, Michelino De Laurentiis, Stefania Cocco, Giuseppina Rea, Annamaria Bonelli, Antonietta Caronna, Maria Cristina Lombari, Gabriele Conforti, Massimiliano Berretta, Gerardo Botti and Nicola Maurea

Int. J. Mol. Sci. 2020, 21(20), 7802; https://doi.org/10.3390/ijms21207802 - 21 Oct 2020

Cited by 51 | Viewed by 5126

Abstract

Hyperglycemia, obesity and metabolic syndrome are negative prognostic factors in breast cancer patients. Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, achieving unprecedented efficacy in multiple malignancies. However, ICIs are associated with immune-related adverse events involving cardiotoxicity. We aimed to study if hyperglycemia [...] Read more.

Hyperglycemia, obesity and metabolic syndrome are negative prognostic factors in breast cancer patients. Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, achieving unprecedented efficacy in multiple malignancies. However, ICIs are associated with immune-related adverse events involving cardiotoxicity. We aimed to study if hyperglycemia could affect ipilimumab-induced anticancer efficacy and enhance its cardiotoxicity. Human cardiomyocytes and estrogen-responsive and triple-negative breast cancer cells (MCF-7 and MDA-MB-231 cell lines) were exposed to ipilimumab under high glucose (25 mM); low glucose (5.5 mM); high glucose and co-administration of SGLT-2 inhibitor (empagliflozin); shifting from high glucose to low glucose. Study of cell viability and the expression of new putative biomarkers of cardiotoxicity and resistance to ICIs (NLRP3, MyD88, cytokines) were quantified through ELISA (Cayman Chemical) methods. Hyperglycemia during treatment with ipilimumab increased cardiotoxicity and reduced mortality of breast cancer cells in a manner that is sensitive to NLRP3. Notably, treatment with ipilimumab and empagliflozin under high glucose or shifting from high glucose to low glucose reduced significantly the magnitude of the effects, increasing responsiveness to ipilimumab and reducing cardiotoxicity. To our knowledge, this is the first evidence that hyperglycemia exacerbates ipilimumab-induced cardiotoxicity and decreases its anticancer efficacy in MCF-7 and MDA-MB-231 cells. This study sets the stage for further tests on other breast cancer cell lines and primary cardiomyocytes and for preclinical trials in mice aimed to decrease glucose through nutritional interventions or administration of gliflozines during treatment with ipilimumab. Full article

(This article belongs to the Special Issue New Prognostic and Predictive Markers in Cancer Progression)

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20 pages, 2286 KiB

Open AccessArticle

Integrated Analysis to Study the Relationship between Tumor-Associated Selenoproteins: Focus on Prostate Cancer

by Francesca Capone, Andrea Polo, Angela Sorice, Alfredo Budillon and Susan Costantini

Int. J. Mol. Sci. 2020, 21(18), 6694; https://doi.org/10.3390/ijms21186694 - 13 Sep 2020

Cited by 4 | Viewed by 2979

Abstract

Selenoproteins are proteins that contain selenium within selenocysteine residues. To date, twenty-five mammalian selenoproteins have been identified; however, the functions of nearly half of these selenoproteins are unknown. Although alterations in selenoprotein expression and function have been suggested to play a role in [...] Read more.

Selenoproteins are proteins that contain selenium within selenocysteine residues. To date, twenty-five mammalian selenoproteins have been identified; however, the functions of nearly half of these selenoproteins are unknown. Although alterations in selenoprotein expression and function have been suggested to play a role in cancer development and progression, few detailed studies have been carried out in this field. Network analyses and data mining of publicly available datasets on gene expression levels in different cancers, and the correlations with patient outcome, represent important tools to study the correlation between selenoproteins and other proteins present in the human interactome, and to determine whether altered selenoprotein expression is cancer type-specific, and/or correlated with cancer patient prognosis. Therefore, in the present study, we used bioinformatics approaches to (i) build up the network of interactions between twenty-five selenoproteins and identify the most inter-correlated proteins/genes, which are named HUB nodes; and (ii) analyze the correlation between selenoprotein gene expression and patient outcome in ten solid tumors. Then, considering the need to confirm by experimental approaches the correlations suggested by the bioinformatics analyses, we decided to evaluate the gene expression levels of the twenty-five selenoproteins and six HUB nodes in androgen receptor-positive (22RV1 and LNCaP) and androgen receptor–negative (DU145 and PC3) cell lines, compared to human nontransformed, and differentiated, prostate epithelial cells (EPN) by RT-qPCR analysis. This analysis confirmed that the combined evaluation of some selenoproteins and HUB nodes could have prognostic value and may improve patient outcome predictions. Full article

(This article belongs to the Special Issue New Prognostic and Predictive Markers in Cancer Progression)

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10 pages, 887 KiB

Open AccessArticle

Transcriptional Profiling of Advanced Urothelial Cancer Predicts Prognosis and Response to Immunotherapy

by Seung-Woo Baek, In-Hwan Jang, Seon-Kyu Kim, Jong-Kil Nam, Sun-Hee Leem and In-Sun Chu

Int. J. Mol. Sci. 2020, 21(5), 1850; https://doi.org/10.3390/ijms21051850 - 8 Mar 2020

Cited by 6 | Viewed by 3728

Abstract

Recent investigations reported that some subtypes from the Lund or The Cancer Genome Atlas (TCGA) classifications were most responsive to PD-L1 inhibitor treatment. However, the association between previously reported subtypes and immune checkpoint inhibitor (ICI) therapy responsiveness has been insufficiently explored. Despite these [...] Read more.

Recent investigations reported that some subtypes from the Lund or The Cancer Genome Atlas (TCGA) classifications were most responsive to PD-L1 inhibitor treatment. However, the association between previously reported subtypes and immune checkpoint inhibitor (ICI) therapy responsiveness has been insufficiently explored. Despite these contributions, the ability to predict the clinical applicability of immune checkpoint inhibitor therapy in patients remains a major challenge. Here, we aimed to re-classify distinct subtypes focusing on ICI responsiveness using gene expression profiling in the IMvigor 210 cohort (n = 298). Based on the hierarchical clustering analysis, we divided advanced urothelial cancer patients into three subgroups. To confirm a prognostic impact, we performed survival analysis and estimated the prognostic value in the IMvigor 210 and TCGA cohort. The activation of CD8⁺ T effector cells was common for patients of classes 2 and 3 in the TCGA and IMvigor 210 cohort. Survival analysis showed that patients of class 3 in the TCGA cohort had a poor prognosis, while patients of class 3 showed considerably prolonged survival in the IMvigor 210 cohort. One of the distinct characteristics of patients in class 3 is the inactivation of the TGFβ and YAP/TAZ pathways and activation of the cell cycle and DNA replication and DNA damage (DDR). Based on our identified transcriptional patterns and the clinical outcomes of advanced urothelial cancer patients, we constructed a schematic summary. When comparing clinical and transcriptome data, patients with downregulation of the TGFβ and YAP/TAZ pathways and upregulation of the cell cycle and DDR may be more responsive to ICI therapy. Full article

(This article belongs to the Special Issue New Prognostic and Predictive Markers in Cancer Progression)

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17 pages, 1621 KiB

Open AccessArticle

N-Cadherin mRNA Levels in Peripheral Blood Could Be a Potential Indicator of New Metastases in Breast Cancer: A Pilot Study

by Takaaki Masuda, Hiroki Ueo, Yuichiro Kai, Miwa Noda, Qingjiang Hu, Kuniaki Sato, Atsushi Fujii, Naoki Hayashi, Yusuke Tsuruda, Hajime Otsu, Yosuke Kuroda, Hidetoshi Eguchi, Shinji Ohno, Koshi Mimori and Hiroaki Ueo

Int. J. Mol. Sci. 2020, 21(2), 511; https://doi.org/10.3390/ijms21020511 - 14 Jan 2020

Cited by 9 | Viewed by 3255

Abstract

Background: There is growing evidence that patients with metastatic breast cancer whose disease progresses from a new metastasis (NM) have a worse prognosis than that of patients whose disease progresses from a pre-existing metastasis. The aim of this pilot study is to identify [...] Read more.

Background: There is growing evidence that patients with metastatic breast cancer whose disease progresses from a new metastasis (NM) have a worse prognosis than that of patients whose disease progresses from a pre-existing metastasis. The aim of this pilot study is to identify a blood biomarker predicting NM in breast cancer. Methods: The expression of epithelial (cytokeratin 18/19) or mesenchymal (plastin-3, vimentin, and N-cadherin) markers in the peripheral blood (PB) of recurrent breast cancer patients undergoing chemotherapy with eribulin or S-1 was measured over the course of treatment by RT-qPCR. The clinical significance of preoperative N-cadherin expression in the PB or tumor tissues of breast cancer patients undergoing curative surgery was assessed by RT-qPCR or using public datasets. Finally, N-cadherin expression in specific PB cell types was assessed by RT-qPCR. Results: The expression levels of the mesenchymal markers N-cadherin and vimentin were high in the NM cases, whereas that of the epithelial marker cytokeratin 18 was high in the pre-existing metastasis cases. High preoperative N-cadherin expression in PB or tumor tissues was significantly associated with poor recurrence-free survival. N-cadherin was expressed mainly in polymorphonuclear leukocytes in PB. Conclusion: N-cadherin mRNA levels in blood may serve as a novel prognostic biomarker predicting NM, including recurrence, in breast cancer patients. Full article

(This article belongs to the Special Issue New Prognostic and Predictive Markers in Cancer Progression)

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9 pages, 826 KiB

Open AccessArticle

Immunohistochemical Analysis Revealed a Correlation between Musashi-2 and Cyclin-D1 Expression in Patients with Oral Squamous Cells Carcinoma

by Giuseppe Troiano, Vito Carlo Alberto Caponio, Gerardo Botti, Gabriella Aquino, Nunzia Simona Losito, Maria Carmela Pedicillo, Khrystyna Zhurakivska, Claudia Arena, Domenico Ciavarella, Filiberto Mastrangelo, Lucio Lo Russo, Lorenzo Lo Muzio and Giuseppe Pannone

Int. J. Mol. Sci. 2020, 21(1), 121; https://doi.org/10.3390/ijms21010121 - 23 Dec 2019

Cited by 9 | Viewed by 2703

Abstract

Aim: Musashi 2 (MSI2), which is an RNA-binding protein, plays a fundamental role in the oncogenesis of several cancers. The aim of this study is to investigate the expression of MSI2 in Oral Squamous Cell Carcinoma (OSCC) and evaluate its correlation to clinic-pathological [...] Read more.

Aim: Musashi 2 (MSI2), which is an RNA-binding protein, plays a fundamental role in the oncogenesis of several cancers. The aim of this study is to investigate the expression of MSI2 in Oral Squamous Cell Carcinoma (OSCC) and evaluate its correlation to clinic-pathological variables and prognosis. Materials and Methods: A bioinformatic analysis was performed on data downloaded from The Cancer Genome Atlas (TCGA) database. The MSI2 expression data were analysed for their correlation with clinic-pathological and prognostic features. In addition, an immmunohistochemical evaluation of MSI2 expression on 108 OSCC samples included in a tissue microarray and 13 healthy mucosae samples was performed. Results: 241 patients’ data from TCGA were included in the final analysis. No DNA mutations were detected for the MSI2 gene, but a hyper methylated condition of the gene emerged. MSI2 mRNA expression correlated with Grading (p = 0.009) and overall survival (p = 0.045), but not with disease free survival (p = 0.549). Males presented a higher MSI2 mRNA expression than females. The immunohistochemical evaluation revealed a weak expression of MSI2 in both OSCC samples and in healthy oral mucosae. In addition, MSI2 expression directly correlated with Cyclin-D1 expression (p = 0.022). However, no correlation has been detected with prognostic outcomes (overall and disease free survival). Conclusions: The role of MSI2 expression in OSCC seems to be not so closely correlated with prognosis, as in other human neoplasms. The correlation with Cyclin-D1 expression suggests an indirect role that MSI2 might have in the proliferation of OSCC cells, but further studies are needed to confirm such results. Full article

(This article belongs to the Special Issue New Prognostic and Predictive Markers in Cancer Progression)

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Review

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15 pages, 656 KiB

Open AccessReview

NAA10 as a New Prognostic Marker for Cancer Progression

by Sun Myung Kim, Eunyoung Ha, Jinyoung Kim, Chiheum Cho, So-Jin Shin and Ji Hae Seo

Int. J. Mol. Sci. 2020, 21(21), 8010; https://doi.org/10.3390/ijms21218010 - 28 Oct 2020

Cited by 17 | Viewed by 3357

Abstract

N-α-acetyltransferase 10 (NAA10) is an acetyltransferase that acetylates both N-terminal amino acid and internal lysine residues of proteins. NAA10 is a crucial player to regulate cell proliferation, migration, differentiation, apoptosis, and autophagy. Recently, mounting evidence presented the overexpression of NAA10 in various types [...] Read more.

N-α-acetyltransferase 10 (NAA10) is an acetyltransferase that acetylates both N-terminal amino acid and internal lysine residues of proteins. NAA10 is a crucial player to regulate cell proliferation, migration, differentiation, apoptosis, and autophagy. Recently, mounting evidence presented the overexpression of NAA10 in various types of cancer, including liver, bone, lung, breast, colon, and prostate cancers, and demonstrated a correlation of overexpressed NAA10 with vascular invasion and metastasis, thereby affecting overall survival rates of cancer patients and recurrence of diseases. This evidence all points NAA10 toward a promising biomarker for cancer prognosis. Here we summarize the current knowledge regarding the biological functions of NAA10 in cancer progression and provide the potential usage of NAA10 as a prognostic marker for cancer progression. Full article

(This article belongs to the Special Issue New Prognostic and Predictive Markers in Cancer Progression)

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11 pages, 378 KiB

Open AccessReview

Head and Neck Paragangliomas—A Genetic Overview

by Anna Majewska, Bartłomiej Budny, Katarzyna Ziemnicka, Marek Ruchała and Małgorzata Wierzbicka

Int. J. Mol. Sci. 2020, 21(20), 7669; https://doi.org/10.3390/ijms21207669 - 16 Oct 2020

Cited by 24 | Viewed by 3390

Abstract

Pheochromocytomas (PCC) and paragangliomas (PGL) are rare neuroendocrine tumors. Head and neck paragangliomas (HNPGL) can be categorized into carotid body tumors, which are the most common, as well as jugular, tympanic, and vagal paraganglioma. A review of the current literature was conducted to [...] Read more.

Pheochromocytomas (PCC) and paragangliomas (PGL) are rare neuroendocrine tumors. Head and neck paragangliomas (HNPGL) can be categorized into carotid body tumors, which are the most common, as well as jugular, tympanic, and vagal paraganglioma. A review of the current literature was conducted to consolidate knowledge concerning PGL mutations, familial occurrence, and the practical application of this information. Available scientific databases were searched using the keywords head and neck paraganglioma and genetics, and 274 articles in PubMed and 1183 in ScienceDirect were found. From these articles, those concerning genetic changes in HNPGLs were selected. The aim of this review is to describe the known genetic changes and their practical applications. We found that the etiology of the tumors in question is based on genetic changes in the form of either germinal or somatic mutations. 40% of PCC and PGL have a predisposing germline mutation (including VHL, SDHB, SDHD, RET, NF1, THEM127, MAX, SDHC, SDHA, SDHAF2, HIF2A, HRAS, KIF1B, PHD2, and FH). Approximately 25–30% of cases are due to somatic mutations, such as RET, VHL, NF1, MAX, and HIF2A. The tumors were divided into three main clusters by the Cancer Genome Atlas (TCGA); namely, the pseudohypoxia group, the Wnt signaling group, and the kinase signaling group. The review also discusses genetic syndromes, epigenetic changes, and new testing technologies such as next-generation sequencing (NGS). Full article

(This article belongs to the Special Issue New Prognostic and Predictive Markers in Cancer Progression)

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29 pages, 1473 KiB

Open AccessReview

Role of Human Leukocyte Antigen System as A Predictive Biomarker for Checkpoint-Based Immunotherapy in Cancer Patients

by Francesco Sabbatino, Luigi Liguori, Giovanna Polcaro, Ilaria Salvato, Gaetano Caramori, Francesco A. Salzano, Vincenzo Casolaro, Cristiana Stellato, Jessica Dal Col and Stefano Pepe

Int. J. Mol. Sci. 2020, 21(19), 7295; https://doi.org/10.3390/ijms21197295 - 2 Oct 2020

Cited by 56 | Viewed by 7819

Abstract

Recent advances in cancer immunotherapy have clearly shown that checkpoint-based immunotherapy is effective in a small subgroup of cancer patients. However, no effective predictive biomarker has been identified so far. The major histocompatibility complex, better known in humans as human leukocyte antigen (HLA), [...] Read more.

Recent advances in cancer immunotherapy have clearly shown that checkpoint-based immunotherapy is effective in a small subgroup of cancer patients. However, no effective predictive biomarker has been identified so far. The major histocompatibility complex, better known in humans as human leukocyte antigen (HLA), is a very polymorphic gene complex consisting of more than 200 genes. It has a crucial role in activating an appropriate host immune response against pathogens and tumor cells by discriminating self and non-self peptides. Several lines of evidence have shown that down-regulation of expression of HLA class I antigen derived peptide complexes by cancer cells is a mechanism of tumor immune escape and is often associated to poor prognosis in cancer patients. In addition, it has also been shown that HLA class I and II antigen expression, as well as defects in the antigen processing machinery complex, may predict tumor responses in cancer immunotherapy. Nevertheless, the role of HLA in predicting tumor responses to checkpoint-based immunotherapy is still debated. In this review, firstly, we will describe the structure and function of the HLA system. Secondly, we will summarize the HLA defects and their clinical significance in cancer patients. Thirdly, we will review the potential role of the HLA as a predictive biomarker for checkpoint-based immunotherapy in cancer patients. Lastly, we will discuss the potential strategies that may restore HLA function to implement novel therapeutic strategies in cancer patients. Full article

(This article belongs to the Special Issue New Prognostic and Predictive Markers in Cancer Progression)

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15 pages, 309 KiB

Open AccessReview

Beyond the Genomic Mutation: Rethinking the Molecular Biomarkers of K-RAS Dependency in Pancreatic Cancers

by Carla Mottini and Luca Cardone

Int. J. Mol. Sci. 2020, 21(14), 5023; https://doi.org/10.3390/ijms21145023 - 16 Jul 2020

Cited by 6 | Viewed by 3272

Abstract

Oncogenic v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (K-RAS) plays a key role in the development and maintenance of pancreatic ductal adenocarcinoma (PDAC). The targeting of K-RAS would be beneficial to treat tumors whose growth depends on active K-RAS. The analysis of K-RAS [...] Read more.

Oncogenic v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (K-RAS) plays a key role in the development and maintenance of pancreatic ductal adenocarcinoma (PDAC). The targeting of K-RAS would be beneficial to treat tumors whose growth depends on active K-RAS. The analysis of K-RAS genomic mutations is a clinical routine; however, an emerging question is whether the mutational status is able to identify tumors effectively dependent on K-RAS for tailoring targeted therapies. With the emergence of novel K-RAS inhibitors in clinical settings, this question is relevant. Several studies support the notion that the K-RAS mutation is not a sufficient biomarker deciphering the effective dependency of the tumor. Transcriptomic and metabolomic profiles of tumors, while revealing K-RAS signaling complexity and K-RAS-driven molecular pathways crucial for PDAC growth, are opening the opportunity to specifically identify K-RAS-dependent- or K-RAS-independent tumor subtypes by using novel molecular biomarkers. This would help tumor selection aimed at tailoring therapies against K-RAS. In this review, we will present studies about how the K-RAS mutation can also be interpreted in a state of K-RAS dependency, for which it is possible to identify specific K-RAS-driven molecular biomarkers in certain PDAC subtypes, beyond the genomic K-RAS mutational status. Full article

(This article belongs to the Special Issue New Prognostic and Predictive Markers in Cancer Progression)

33 pages, 521 KiB

Open AccessReview

Biomarkers in Triple-Negative Breast Cancer: State-of-the-Art and Future Perspectives

by Stefania Cocco, Michela Piezzo, Alessandra Calabrese, Daniela Cianniello, Roberta Caputo, Vincenzo Di Lauro, Giuseppina Fusco, Germira di Gioia, Marina Licenziato and Michelino de Laurentiis

Int. J. Mol. Sci. 2020, 21(13), 4579; https://doi.org/10.3390/ijms21134579 - 27 Jun 2020

Cited by 76 | Viewed by 8013

Abstract

Triple-negative breast cancer (TNBC) is a heterogeneous group of tumors characterized by aggressive behavior, high risk of distant recurrence, and poor survival. Chemotherapy is still the main therapeutic approach for this subgroup of patients, therefore, progress in the treatment of TNBC remains an [...] Read more.

Triple-negative breast cancer (TNBC) is a heterogeneous group of tumors characterized by aggressive behavior, high risk of distant recurrence, and poor survival. Chemotherapy is still the main therapeutic approach for this subgroup of patients, therefore, progress in the treatment of TNBC remains an important challenge. Data derived from molecular technologies have identified TNBCs with different gene expression and mutation profiles that may help developing targeted therapies. So far, however, only a few of these have shown to improve the prognosis and outcomes of TNBC patients. Robust predictive biomarkers to accelerate clinical progress are needed. Herein, we review prognostic and predictive biomarkers in TNBC, discuss the current evidence supporting their use, and look at the future of this research field. Full article

(This article belongs to the Special Issue New Prognostic and Predictive Markers in Cancer Progression)

16 pages, 729 KiB

Open AccessReview

MicroRNAs as Key Players in Melanoma Cell Resistance to MAPK and Immune Checkpoint Inhibitors

by Maria Letizia Motti, Michele Minopoli, Gioconda Di Carluccio, Paolo Antonio Ascierto and Maria Vincenza Carriero

Int. J. Mol. Sci. 2020, 21(12), 4544; https://doi.org/10.3390/ijms21124544 - 26 Jun 2020

Cited by 25 | Viewed by 3974

Abstract

Advances in the use of targeted and immune therapies have revolutionized the clinical management of melanoma patients, prolonging significantly their overall and progression-free survival. However, both targeted and immune therapies suffer limitations due to genetic mutations and epigenetic modifications, which determine a great [...] Read more.

Advances in the use of targeted and immune therapies have revolutionized the clinical management of melanoma patients, prolonging significantly their overall and progression-free survival. However, both targeted and immune therapies suffer limitations due to genetic mutations and epigenetic modifications, which determine a great heterogeneity and phenotypic plasticity of melanoma cells. Acquired resistance of melanoma patients to inhibitors of BRAF (BRAFi) and MEK (MEKi), which block the mitogen-activated protein kinase (MAPK) pathway, limits their prolonged use. On the other hand, immune checkpoint inhibitors improve the outcomes of patients in only a subset of them and the molecular mechanisms underlying lack of responses are under investigation. There is growing evidence that altered expression levels of microRNAs (miRNA)s induce drug-resistance in tumor cells and that restoring normal expression of dysregulated miRNAs may re-establish drug sensitivity. However, the relationship between specific miRNA signatures and acquired resistance of melanoma to MAPK and immune checkpoint inhibitors is still limited and not fully elucidated. In this review, we provide an updated overview of how miRNAs induce resistance or restore melanoma cell sensitivity to mitogen-activated protein kinase inhibitors (MAPKi) as well as on the relationship existing between miRNAs and immune evasion by melanoma cell resistant to MAPKi. Full article

(This article belongs to the Special Issue New Prognostic and Predictive Markers in Cancer Progression)

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47 pages, 2850 KiB

Open AccessReview

The PI3K-AKT-mTOR Pathway and Prostate Cancer: At the Crossroads of AR, MAPK, and WNT Signaling

by Boris Y. Shorning, Manisha S. Dass, Matthew J. Smalley and Helen B. Pearson

Int. J. Mol. Sci. 2020, 21(12), 4507; https://doi.org/10.3390/ijms21124507 - 25 Jun 2020

Cited by 358 | Viewed by 22005

Abstract

Oncogenic activation of the phosphatidylinositol-3-kinase (PI3K), protein kinase B (PKB/AKT), and mammalian target of rapamycin (mTOR) pathway is a frequent event in prostate cancer that facilitates tumor formation, disease progression and therapeutic resistance. Recent discoveries indicate that the complex crosstalk between the PI3K-AKT-mTOR [...] Read more.

Oncogenic activation of the phosphatidylinositol-3-kinase (PI3K), protein kinase B (PKB/AKT), and mammalian target of rapamycin (mTOR) pathway is a frequent event in prostate cancer that facilitates tumor formation, disease progression and therapeutic resistance. Recent discoveries indicate that the complex crosstalk between the PI3K-AKT-mTOR pathway and multiple interacting cell signaling cascades can further promote prostate cancer progression and influence the sensitivity of prostate cancer cells to PI3K-AKT-mTOR-targeted therapies being explored in the clinic, as well as standard treatment approaches such as androgen-deprivation therapy (ADT). However, the full extent of the PI3K-AKT-mTOR signaling network during prostate tumorigenesis, invasive progression and disease recurrence remains to be determined. In this review, we outline the emerging diversity of the genetic alterations that lead to activated PI3K-AKT-mTOR signaling in prostate cancer, and discuss new mechanistic insights into the interplay between the PI3K-AKT-mTOR pathway and several key interacting oncogenic signaling cascades that can cooperate to facilitate prostate cancer growth and drug-resistance, specifically the androgen receptor (AR), mitogen-activated protein kinase (MAPK), and WNT signaling cascades. Ultimately, deepening our understanding of the broader PI3K-AKT-mTOR signaling network is crucial to aid patient stratification for PI3K-AKT-mTOR pathway-directed therapies, and to discover new therapeutic approaches for prostate cancer that improve patient outcome. Full article

(This article belongs to the Special Issue New Prognostic and Predictive Markers in Cancer Progression)

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25 pages, 624 KiB

Open AccessReview

Insight toward the MicroRNA Profiling of Laryngeal Cancers: Biological Role and Clinical Impact

by Takashi Takeuchi, Hiromichi Kawasaki, Amalia Luce, Alessia Maria Cossu, Gabriella Misso, Marianna Scrima, Marco Bocchetti, Filippo Ricciardiello, Michele Caraglia and Silvia Zappavigna

Int. J. Mol. Sci. 2020, 21(10), 3693; https://doi.org/10.3390/ijms21103693 - 24 May 2020

Cited by 25 | Viewed by 4257

Abstract

Head and neck squamous cell carcinoma (HNSCC), a heterogeneous disease arising from various anatomical locations including the larynx, is a leading cause of death worldwide. Despite advances in multimodality treatment, the overall survival rate of the disease is still largely dismal. Early and [...] Read more.

Head and neck squamous cell carcinoma (HNSCC), a heterogeneous disease arising from various anatomical locations including the larynx, is a leading cause of death worldwide. Despite advances in multimodality treatment, the overall survival rate of the disease is still largely dismal. Early and accurate diagnosis of HNSCC is urgently demanded in order to prevent cancer progression and to improve the quality of the patient’s life. Recently, microRNAs (miRNAs), a family of small non-coding RNAs, have been widely reported as new robust tools for prediction, diagnosis, prognosis, and therapeutic approaches of human diseases. Abnormally expressed miRNAs are strongly associated with cancer development, resistance to chemo-/radiotherapy, and metastatic potential through targeting a large variety of genes. In this review, we summarize on the recent reports that emphasize the pivotal biological roles of miRNAs in regulating carcinogenesis of HNSCC, particularly laryngeal cancer. In more detail, we report the characterized miRNAs with an evident either oncogenic or tumor suppressive role in the cancers. In addition, we also focus on the correlation between miRNA deregulation and clinical relevance in cancer patients. On the basis of intriguing findings, the study of miRNAs will provide a new great opportunity to access better clinical management of the malignancies. Full article

(This article belongs to the Special Issue New Prognostic and Predictive Markers in Cancer Progression)

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