Current Issues in Molecular Biology

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6 pages, 385 KiB

Open AccessEditorial

Advanced Molecular Solutions for Cancer Therapy—The Good, the Bad, and the Ugly of the Biomarker Paradigm

by Dumitru Andrei Iacobas

Curr. Issues Mol. Biol. 2024, 46(3), 1694-1699; https://doi.org/10.3390/cimb46030109 - 22 Feb 2024

Cited by 1 | Viewed by 1094

Abstract

Identifying the most effective actionable molecules whose “smart” manipulation might selectively kill/slow down/stop the proliferation of cancer cells, with few side effects on the normal cells of the tissue, was for decades the single major objective of countless investigators [...] Full article

(This article belongs to the Special Issue Advanced Molecular Solutions for Cancer Therapy)

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Research

Jump to: Editorial, Review, Other

28 pages, 3190 KiB

Open AccessArticle

Unveiling the Molecular Mechanism of Trastuzumab Resistance in SKBR3 and BT474 Cell Lines for HER2 Positive Breast Cancer

by Anna Kokot, Sachin Gadakh, Indrajit Saha, Ewa Gajda, Michał Łaźniewski, Somnath Rakshit, Kaustav Sengupta, Ayatullah Faruk Mollah, Michał Denkiewicz, Katarzyna Górczak, Jürgen Claesen, Tomasz Burzykowski and Dariusz Plewczynski

Curr. Issues Mol. Biol. 2024, 46(3), 2713-2740; https://doi.org/10.3390/cimb46030171 - 21 Mar 2024

Cited by 2 | Viewed by 2517

Abstract

HER2-positive breast cancer is one of the most prevalent forms of cancer among women worldwide. Generally, the molecular characteristics of this breast cancer include activation of human epidermal growth factor receptor-2 (HER2) and hormone receptor activation. HER2-positive is associated with a higher death [...] Read more.

HER2-positive breast cancer is one of the most prevalent forms of cancer among women worldwide. Generally, the molecular characteristics of this breast cancer include activation of human epidermal growth factor receptor-2 (HER2) and hormone receptor activation. HER2-positive is associated with a higher death rate, which led to the development of a monoclonal antibody called trastuzumab, specifically targeting HER2. The success rate of HER2-positive breast cancer treatment has been increased; however, drug resistance remains a challenge. This fact motivated us to explore the underlying molecular mechanisms of trastuzumab resistance. For this purpose, a two-fold approach was taken by considering well-known breast cancer cell lines SKBR3 and BT474. In the first fold, trastuzumab treatment doses were optimized separately for both cell lines. This was done based on the proliferation rate of cells in response to a wide variety of medication dosages. Thereafter, each cell line was cultivated with a steady dosage of herceptin for several months. During this period, six time points were selected for further in vitro analysis, ranging from the untreated cell line at the beginning to a fully resistant cell line at the end of the experiment. In the second fold, nucleic acids were extracted for further high throughput-based microarray experiments of gene and microRNA expression. Such expression data were further analyzed in order to infer the molecular mechanisms involved in the underlying development of trastuzumab resistance. In the list of differentially expressed genes and miRNAs, multiple genes (e.g., BIRC5, E2F1, TFRC, and USP1) and miRNAs (e.g., hsa miR 574 3p, hsa miR 4530, and hsa miR 197 3p) responsible for trastuzumab resistance were found. Downstream analysis showed that TFRC, E2F1, and USP1 were also targeted by hsa-miR-8485. Moreover, it indicated that miR-4701-5p was highly expressed as compared to TFRC in the SKBR3 cell line. These results unveil key genes and miRNAs as molecular regulators for trastuzumab resistance. Full article

(This article belongs to the Special Issue Advanced Molecular Solutions for Cancer Therapy)

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15 pages, 8204 KiB

Open AccessArticle

Analysis of Somatic Mutations in the TCGA-LIHC Whole Exome Sequence to Identify the Neoantigen for Immunotherapy in Hepatocellular Carcinoma

by Swetha Pulakuntla, Khajamohiddin Syed and Vaddi Damodara Reddy

Curr. Issues Mol. Biol. 2024, 46(1), 106-120; https://doi.org/10.3390/cimb46010009 - 22 Dec 2023

Cited by 1 | Viewed by 1683

Abstract

There are numerous clinically proven methods for treating cancer worldwide. Immunotherapy has been used to treat cancer with significant success in the current studies. The purpose of this work is to identify somatically altered target gene neoantigens and investigate liver cancer-related immune cell [...] Read more.

There are numerous clinically proven methods for treating cancer worldwide. Immunotherapy has been used to treat cancer with significant success in the current studies. The purpose of this work is to identify somatically altered target gene neoantigens and investigate liver cancer-related immune cell interaction and functional changes for potential immunotherapy in future clinical trials. Clinical patient data from the Cancer Genome Atlas (TCGA) database were used in this investigation. The R maf utility package was used to perform somatic analysis. The 17-mer peptide neoantigens were extracted using an in-house Python software called Peptide.py. Additionally, the epitope analysis was conducted using NetMHCpan4.1 program. Neopeptide immunogenicity was assessed using DeepCNN-Ineo, and tumor immune interaction, association with immune cells, correlation, and survival analysis were assessed using the TIMER web server. Based on somatic mutation analysis, we have identified the top 10 driver genes (TP53, TNN, CTNNB1, MUC16, ALB, PCLO, MUC4, ABCA13, APOB, and RYR2). From the superfamily of 20 HLA (Human leukocyte antigens) allele epitopes, we discovered 5653 neopeptides. Based on T cell receptor face hydrophobic analysis, these neopeptides were subjected to immunogenicity investigation. A mutation linked to tumor growth may have an impact on immune cells. According to this study’s correlation and survival analysis, all driver genes may function as immune targets for liver cancer. These genes are recognized to be immune targets. In the future, immune checkpoint inhibitors may be developed to prolong patient survival times and prevent hepatocellular carcinoma (HCC) through immunotherapy. Full article

(This article belongs to the Special Issue Advanced Molecular Solutions for Cancer Therapy)

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13 pages, 2378 KiB

Open AccessArticle

Activation of Adrenoceptor Alpha-2 (ADRA2A) Promotes Chemosensitization to Carboplatin in Ovarian Cancer Cell Lines

by Haya Albanna, Alesia Gjoni, Danielle Robinette, Gerardo Rodriguez, Lora Djambov, Margaret E. Olson and Peter C. Hart

Curr. Issues Mol. Biol. 2023, 45(12), 9566-9578; https://doi.org/10.3390/cimb45120598 - 28 Nov 2023

Cited by 2 | Viewed by 1868

Abstract

Recurrence of ovarian cancer (OvCa) following surgery and standard carboplatin/paclitaxel first-line therapy signifies poor median progression-free survival (<24 months) in the majority of patients with OvCa. The current study utilized unbiased high-throughput screening (HTS) to evaluate an FDA-approved compound library for drugs that [...] Read more.

Recurrence of ovarian cancer (OvCa) following surgery and standard carboplatin/paclitaxel first-line therapy signifies poor median progression-free survival (<24 months) in the majority of patients with OvCa. The current study utilized unbiased high-throughput screening (HTS) to evaluate an FDA-approved compound library for drugs that could be repurposed to improve OvCa sensitivity to carboplatin. The initial screen revealed six compounds with agonistic activity for the adrenoceptor alpha-2a (ADRA2A). These findings were validated in multiple OvCa cell lines (TYKnu, CAOV3, OVCAR8) using three ADRA2A agonists (xylazine, dexmedetomidine, and clonidine) and two independent viability assays. In all the experiments, these compounds enhanced the cytotoxicity of carboplatin treatment. Genetic overexpression of ADRA2A was also sufficient to reduce cell viability and increase carboplatin sensitivity. Taken together, these data indicate that ADRA2A activation may promote chemosensitivity in OvCa, which could be targeted by widely used medications currently indicated for other disease states. Full article

(This article belongs to the Special Issue Advanced Molecular Solutions for Cancer Therapy)

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29 pages, 8209 KiB

Open AccessArticle

Genomic Fabrics of the Excretory System’s Functional Pathways Remodeled in Clear Cell Renal Cell Carcinoma

by Dumitru Andrei Iacobas, Ehiguese Alade Obiomon and Sanda Iacobas

Curr. Issues Mol. Biol. 2023, 45(12), 9471-9499; https://doi.org/10.3390/cimb45120594 - 24 Nov 2023

Cited by 3 | Viewed by 1328

Abstract

Clear cell renal cell carcinoma (ccRCC) is the most frequent form of kidney cancer. Metastatic stages of ccRCC reduce the five-year survival rate to 15%. In this report, we analyze the ccRCC-induced remodeling of the five KEGG-constructed excretory functional pathways in a surgically [...] Read more.

Clear cell renal cell carcinoma (ccRCC) is the most frequent form of kidney cancer. Metastatic stages of ccRCC reduce the five-year survival rate to 15%. In this report, we analyze the ccRCC-induced remodeling of the five KEGG-constructed excretory functional pathways in a surgically removed right kidney and its metastasis in the chest wall from the perspective of the Genomic Fabric Paradigm (GFP). The GFP characterizes every single gene in each region by these independent variables: the average expression level (AVE), relative expression variability (REV), and expression correlation (COR) with each other gene. While the traditional approach is limited to only AVE analysis, the novel REV analysis identifies the genes whose correct expression level is critical for cell survival and proliferation. The COR analysis determines the real gene networks responsible for functional pathways. The analyses covered the pathways for aldosterone-regulated sodium reabsorption, collecting duct acid secretion, endocrine and other factor-regulated sodium reabsorption, proximal tubule bicarbonate reclamation, and vasopressin-regulated water reabsorption. The present study confirms the conclusion of our previously published articles on prostate and kidney cancers that even equally graded cancer nodules from the same tumor have different transcriptomic topologies. Therefore, the personalization of anti-cancer therapy should go beyond the individual, to his/her major cancer nodules. Full article

(This article belongs to the Special Issue Advanced Molecular Solutions for Cancer Therapy)

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15 pages, 5760 KiB

Open AccessArticle

T-Lymphocytes Activated by Dendritic Cells Loaded by Tumor-Derived Vesicles Decrease Viability of Melanoma Cells In Vitro

by Ivan Yurevich Filin, Yuriy Pavlovich Mayasin, Chulpan Bulatovna Kharisova, Anna Valerevna Gorodilova, Daria Sergeevna Chulpanova, Kristina Viktorovna Kitaeva, Albert Anatolyevich Rizvanov and Valeria Vladimirovna Solovyeva

Curr. Issues Mol. Biol. 2023, 45(10), 7827-7841; https://doi.org/10.3390/cimb45100493 - 26 Sep 2023

Cited by 3 | Viewed by 1689

Abstract

Immunotherapy represents an innovative approach to cancer treatment, based on activating the body’s own immune system to combat tumor cells. Among various immunotherapy strategies, dendritic cell vaccines hold a special place due to their ability to activate T-lymphocytes, key players in cellular immunity, [...] Read more.

Immunotherapy represents an innovative approach to cancer treatment, based on activating the body’s own immune system to combat tumor cells. Among various immunotherapy strategies, dendritic cell vaccines hold a special place due to their ability to activate T-lymphocytes, key players in cellular immunity, and direct them to tumor cells. In this study, the influence of dendritic cells processed with tumor-derived vesicles on the viability of melanoma cells in vitro was investigated. Dendritic cells were loaded with tumor-derived vesicles, after which they were used to activate T-cells. The study demonstrated that such modified T-cells exhibit high activity against melanoma cells, leading to a decrease in their viability. Our analysis highlights the potential efficacy of this approach in developing immunotherapy against melanoma. These results provide new prospects for further research and the development of antitumor strategies based on the mechanisms of T-lymphocyte activation using tumor-derived vesicles. Full article

(This article belongs to the Special Issue Advanced Molecular Solutions for Cancer Therapy)

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16 pages, 2109 KiB

Open AccessArticle

Targeted Delivery of Chimeric Antigen Receptor into T Cells via CRISPR-Mediated Homology-Directed Repair with a Dual-AAV6 Transduction System

by Pablo D. Moço, Omar Farnós, David Sharon and Amine A. Kamen

Curr. Issues Mol. Biol. 2023, 45(10), 7705-7720; https://doi.org/10.3390/cimb45100486 - 22 Sep 2023

Cited by 3 | Viewed by 2600

Abstract

CAR-T cell therapy involves genetically engineering T cells to recognize and attack tumour cells by adding a chimeric antigen receptor (CAR) to their surface. In this study, we have used dual transduction with AAV serotype 6 (AAV6) to integrate an anti-CD19 CAR into [...] Read more.

CAR-T cell therapy involves genetically engineering T cells to recognize and attack tumour cells by adding a chimeric antigen receptor (CAR) to their surface. In this study, we have used dual transduction with AAV serotype 6 (AAV6) to integrate an anti-CD19 CAR into human T cells at a known genomic location. The first viral vector expresses the Cas9 endonuclease and a guide RNA (gRNA) targeting the T cell receptor alpha constant locus, while the second vector carries the DNA template for homology-mediated CAR insertion. We evaluated three gRNA candidates and determined their efficiency in generating indels. The AAV6 successfully delivered the CRISPR/Cas9 machinery in vitro, and molecular analysis of the dual transduction showed the integration of the CAR transgene into the desired location. In contrast to the random integration methods typically used to generate CAR-T cells, targeted integration into a known genomic locus can potentially lower the risk of insertional mutagenesis and provide more stable levels of CAR expression. Critically, this method also results in the knockout of the endogenous T cell receptor, allowing target cells to be derived from allogeneic donors. This raises the exciting possibility of “off-the-shelf” universal immunotherapies that would greatly simplify the production and administration of CAR-T cells. Full article

(This article belongs to the Special Issue Advanced Molecular Solutions for Cancer Therapy)

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16 pages, 2905 KiB

Open AccessArticle

2-Methoxyestradiol as an Antiproliferative Agent for Long-Term Estrogen-Deprived Breast Cancer Cells

by Masayo Hirao-Suzuki, Koki Kanameda, Masufumi Takiguchi, Narumi Sugihara and Shuso Takeda

Curr. Issues Mol. Biol. 2023, 45(9), 7336-7351; https://doi.org/10.3390/cimb45090464 - 9 Sep 2023

Cited by 2 | Viewed by 1594

Abstract

To identify effective treatment modalities for breast cancer with acquired resistance, we first compared the responsiveness of estrogen receptor-positive breast cancer MCF-7 cells and long-term estrogen-deprived (LTED) cells (a cell model of endocrine therapy-resistant breast cancer) derived from MCF-7 cells to G-1 and [...] Read more.

To identify effective treatment modalities for breast cancer with acquired resistance, we first compared the responsiveness of estrogen receptor-positive breast cancer MCF-7 cells and long-term estrogen-deprived (LTED) cells (a cell model of endocrine therapy-resistant breast cancer) derived from MCF-7 cells to G-1 and 2-methoxyestradiol (2-MeO-E2), which are microtubule-destabilizing agents and agonists of the G protein-coupled estrogen receptor 1 (GPER1). The expression of GPER1 in LTED cells was low (~0.44-fold), and LTED cells displayed approximately 1.5-fold faster proliferation than MCF-7 cells. Although G-1 induced comparable antiproliferative effects on both MCF-7 and LTED cells (IC₅₀ values of >10 µM), 2-MeO-E2 exerted antiproliferative effects selective for LTED cells with an IC₅₀ value of 0.93 μM (vs. 6.79 μM for MCF-7 cells) and induced G2/M cell cycle arrest. Moreover, we detected higher amounts of β-tubulin proteins in LTED cells than in MCF-7 cells. Among the β-tubulin (TUBB) isotype genes, the highest expression of TUBB2B (~3.2-fold) was detected in LTED cells compared to that in MCF-7 cells. Additionally, siTUBB2B restores 2-MeO-E2-mediated inhibition of LTED cell proliferation. Other microtubule-targeting agents, i.e., paclitaxel, nocodazole, and colchicine, were not selective for LTED cells. Therefore, 2-MeO-E2 can be an antiproliferative agent to suppress LTED cell proliferation. Full article

(This article belongs to the Special Issue Advanced Molecular Solutions for Cancer Therapy)

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9 pages, 1039 KiB

Open AccessCommunication

HLA-G 14 bp Ins/Del (rs66554220) Variant Is Not Associated with Breast Cancer in Women from Western Mexico

by Denisse Stephania Becerra-Loaiza, Luisa Fernanda Roldan Flores, Luis Antonio Ochoa-Ramírez, Bricia M. Gutiérrez-Zepeda, Alicia Del Toro-Arreola, Ramón Antonio Franco-Topete, Andrés Morán-Mendoza, Antonio Oceguera-Villanueva, Antonio Topete, David Javalera, Antonio Quintero-Ramos and Adrián Daneri-Navarro

Curr. Issues Mol. Biol. 2023, 45(8), 6842-6850; https://doi.org/10.3390/cimb45080432 - 16 Aug 2023

Cited by 1 | Viewed by 1675

Abstract

HLA-G is a physiology and pathologic immunomodulator detrimentally related to cancer. Its gene is heavily transcriptionally and post-transcriptionally regulated by variants located in regulator regions like 3′UTR, being the most studied Ins/Del of 14-bp (rs66554220), which is known to influence the effects of [...] Read more.

HLA-G is a physiology and pathologic immunomodulator detrimentally related to cancer. Its gene is heavily transcriptionally and post-transcriptionally regulated by variants located in regulator regions like 3′UTR, being the most studied Ins/Del of 14-bp (rs66554220), which is known to influence the effects of endogen cell factors; nevertheless, the reports are discrepant and controversial. Herein, the relationship of the 14-bp Ins/Del variant (rs66554220) with breast cancer (BC) and its clinical characteristics were analyzed in 182 women with non-familial BC and 221 disease-free women as a reference group. Both groups from western Mexico and sex–age-matched (sm-RG). The rs66554220 variant was amplified by SSP-PCR and the fragments were visualized in polyacrylamide gel electrophoresis. The variant rs66554220 was not associated with BC in our population. However, we suggest the Ins allele as a possible risk factor for developing BC at clinical stage IV (OR = 3.05, 95% CI = 1.16–7.96, p = 0.01); nevertheless, given the small stratified sample size (n = 11, statistical power = 41%), this is inconclusive. In conclusion, the 14-bp Ins/Del (rs66554220) variant of HLA-G is not associated with BC in the Mexican population, but might be related to advanced breast tumors. Further studies are required. Full article

(This article belongs to the Special Issue Advanced Molecular Solutions for Cancer Therapy)

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16 pages, 2669 KiB

Open AccessArticle

Identification of a Novel ERK5 (MAPK7) Inhibitor, MHJ-627, and Verification of Its Potent Anticancer Efficacy in Cervical Cancer HeLa Cells

by Jeonghye Hwang, Hyejin Moon, Hakwon Kim and Ki-Young Kim

Curr. Issues Mol. Biol. 2023, 45(7), 6154-6169; https://doi.org/10.3390/cimb45070388 - 24 Jul 2023

Cited by 3 | Viewed by 2478

Abstract

Extracellular signal-regulated kinase 5 (ERK5), a member of the mitogen-activated protein kinase (MAPK) family, is involved in key cellular processes. However, overexpression and upregulation of ERK5 have been reported in various cancers, and ERK5 is associated with almost every biological characteristic of cancer [...] Read more.

Extracellular signal-regulated kinase 5 (ERK5), a member of the mitogen-activated protein kinase (MAPK) family, is involved in key cellular processes. However, overexpression and upregulation of ERK5 have been reported in various cancers, and ERK5 is associated with almost every biological characteristic of cancer cells. Accordingly, ERK5 has become a novel target for the development of anticancer drugs as inhibition of ERK5 shows suppressive effects of the deleterious properties of cancer cells. Herein, we report the synthesis and identification of a novel ERK5 inhibitor, MHJ-627, and verify its potent anticancer efficacy in a yeast model and the cervical cancer HeLa cell line. MHJ-627 successfully inhibited the kinase activity of ERK5 (IC₅₀: 0.91 μM) and promoted the mRNA expression of tumor suppressors and anti-metastatic genes. Moreover, we observed significant cancer cell death, accompanied by a reduction in mRNA levels of the cell proliferation marker, proliferating cell nuclear antigen (PCNA), following ERK5 inhibition due to MHJ-627 treatment. We expect this finding to serve as a lead compound for further identification of inhibitors for ERK5-directed novel approaches for oncotherapy with increased specificity. Full article

(This article belongs to the Special Issue Advanced Molecular Solutions for Cancer Therapy)

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13 pages, 3072 KiB

Open AccessArticle

A Comparative Analysis of NOX4 Protein Expression in Malignant and Non-Malignant Thyroid Tumors

by Salma Fenniche, Mohamed Oukabli, Yassire Oubaddou, Hafsa Chahdi, Amal Damiri, Abir Alghuzlan, Abdelilah Laraqui, Nadia Dakka, Youssef Bakri, Corinne Dupuy and Rabii Ameziane El Hassani

Curr. Issues Mol. Biol. 2023, 45(7), 5811-5823; https://doi.org/10.3390/cimb45070367 - 13 Jul 2023

Cited by 4 | Viewed by 1854

Abstract

The comparative analysis of the expression of the reactive oxygen species-generating NADPH oxidase NOX4 from TCGA data shows that the NOX4 transcript is upregulated in papillary thyroid carcinomas (PTC)-BRAF^V600E tumors compared to PTC-BRAF^wt tumors. However, a comparative analysis of NOX4 at [...] Read more.

The comparative analysis of the expression of the reactive oxygen species-generating NADPH oxidase NOX4 from TCGA data shows that the NOX4 transcript is upregulated in papillary thyroid carcinomas (PTC)-BRAF^V600E tumors compared to PTC-BRAF^wt tumors. However, a comparative analysis of NOX4 at the protein level in malignant and non-malignant tumors is missing. We explored NOX4 protein expression by immunohistochemistry staining in malignant tumors (28 classical forms of PTC (C-PTC), 17 follicular variants of PTC (F-PTC), and three anaplastic thyroid carcinomas (ATCs)) and in non-malignant tumors (six lymphocytic thyroiditis, four Graves’ disease, ten goiters, and 20 hyperplasias). We detected the BRAF^V600E mutation by Sanger sequencing and digital droplet PCR. The results show that NOX4 was found to be higher (score ≥ 2) in C-PTC (92.9%) compared to F-PTC (52.9%) and ATC (33.3%) concerning malignant tumors. Interestingly, all C-PTC-BRAF^V600E expressed a high score for NOX4 at the protein level, strengthening the positive correlation between the BRAF^V600E mutation and NOX4 expression. In addition, independent of the mutational status of BRAF, we observed that 90% of C-PTC infiltrating tumors showed high NOX4 expression, suggesting that NOX4 may be considered a complementary biomarker in PTC aggressiveness. Interestingly, NOX4 was highly expressed in non-malignant thyroid diseases with different subcellular localizations. Full article

(This article belongs to the Special Issue Advanced Molecular Solutions for Cancer Therapy)

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15 pages, 1806 KiB

Open AccessArticle

Potential Diagnostic Value of Salivary Tumor Markers in Breast, Lung and Ovarian Cancer: A Preliminary Study

by Lyudmila V. Bel’skaya, Elena A. Sarf, Alexandra I. Loginova, Dmitry M. Vyushkov and En Djun Choi

Curr. Issues Mol. Biol. 2023, 45(6), 5084-5098; https://doi.org/10.3390/cimb45060323 - 10 Jun 2023

Cited by 4 | Viewed by 2810

Abstract

The aim of the study was to determine the content of tumor markers for breast, lung and ovarian cancer in saliva, as well as for benign diseases of the corresponding organs and in the control group, and to evaluate their diagnostic significance. Strictly [...] Read more.

The aim of the study was to determine the content of tumor markers for breast, lung and ovarian cancer in saliva, as well as for benign diseases of the corresponding organs and in the control group, and to evaluate their diagnostic significance. Strictly before the start of treatment, saliva samples were obtained and the concentrations of tumor markers (AFP, NSE, HE4, CA15-3, CA72-4, CA125 and CEA) were determined using an enzyme immunoassay (ELISA). CA125 and HE4 were simultaneously determined to be in the blood serum of patients with ovarian cancer. The concentrations of salivary CEA, NSE, CA15-3, CA72-4 and CA125 of the control group were significantly lower than in oncological diseases; however, these tumor markers also increased in saliva with benign diseases. The content of tumor markers depends on the stage of cancer, and the presence of lymph node metastasis; however, the identified patterns are statistically unreliable. The determination of HE4 and AFP in saliva was not informative. In general, the area of potential use of tumor markers in saliva is extremely narrow. Thus, CEA may be diagnostic for breast and lung cancer, but not for ovarian cancer. CA72-4 is most informative for ovarian mucinous carcinoma. None of the markers showed significant differences between malignant and non-malignant pathologies. Full article

(This article belongs to the Special Issue Advanced Molecular Solutions for Cancer Therapy)

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16 pages, 1770 KiB

Open AccessArticle

Potential Diagnostic Biomarker Detection for Prostate Cancer Using Untargeted and Targeted Metabolomic Profiling

by Diana Nitusca, Carmen Socaciu, Andreea Iulia Socaciu, Ioan Ovidiu Sirbu, Razvan Bardan, Alin Adrian Cumpanas, Edward Seclaman and Catalin Marian

Curr. Issues Mol. Biol. 2023, 45(6), 5036-5051; https://doi.org/10.3390/cimb45060320 - 8 Jun 2023

Cited by 1 | Viewed by 1860

Abstract

Prostate cancer (PCa) remains one of the leading causes of cancer mortality in men worldwide, currently lacking specific, early detection and staging biomarkers. In this regard, modern research focuses efforts on the discovery of novel molecules that could represent potential future non-invasive biomarkers [...] Read more.

Prostate cancer (PCa) remains one of the leading causes of cancer mortality in men worldwide, currently lacking specific, early detection and staging biomarkers. In this regard, modern research focuses efforts on the discovery of novel molecules that could represent potential future non-invasive biomarkers for the diagnosis of PCa, as well as therapeutic targets. Mounting evidence shows that cancer cells express an altered metabolism in their early stages, making metabolomics a promising tool for the discovery of altered pathways and potential biomarker molecules. In this study, we first performed untargeted metabolomic profiling on 48 PCa plasma samples and 23 healthy controls using ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-[ESI+]-MS) for the discovery of metabolites with altered profiles. Secondly, we selected five molecules (L-proline, L-tryptophan, acetylcarnitine, lysophosphatidylcholine C18:2 and spermine) for the downstream targeted metabolomics and found out that all the molecules, regardless of the PCa stage, were decreased in the PCa plasma samples when compared to the controls, making them potential biomarkers for PCa detection. Moreover, spermine, acetylcarnitine and L-tryptophan had very high diagnostic accuracy, with AUC values of 0.992, 0.923 and 0.981, respectively. Consistent with other literature findings, these altered metabolites could represent future specific and non-invasive candidate biomarkers for PCa detection, which opens novel horizons in the field of metabolomics. Full article

(This article belongs to the Special Issue Advanced Molecular Solutions for Cancer Therapy)

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10 pages, 1938 KiB

Open AccessCommunication

DDIT4 Downregulation by siRNA Approach Increases the Activity of Proteins Regulating Fatty Acid Metabolism upon Aspirin Treatment in Human Breast Cancer Cells

by Aistė Savukaitytė, Agnė Bartnykaitė, Justina Bekampytė, Rasa Ugenskienė and Elona Juozaitytė

Curr. Issues Mol. Biol. 2023, 45(6), 4665-4674; https://doi.org/10.3390/cimb45060296 - 28 May 2023

Cited by 2 | Viewed by 2239

Abstract

Repositioning of aspirin for a more effective breast cancer (BC) treatment requires identification of predictive biomarkers. However, the molecular mechanism underlying the anticancer activity of aspirin remains fully undefined. Cancer cells enhance de novo fatty acid (FA) synthesis and FA oxidation to maintain [...] Read more.

Repositioning of aspirin for a more effective breast cancer (BC) treatment requires identification of predictive biomarkers. However, the molecular mechanism underlying the anticancer activity of aspirin remains fully undefined. Cancer cells enhance de novo fatty acid (FA) synthesis and FA oxidation to maintain a malignant phenotype, and the mechanistic target of rapamycin (mTORC1) is required for lipogenesis. We, therefore, aimed to test if the expression of mTORC1 suppressor DNA damage-inducible transcript (DDIT4) affects the activity of main enzymes in FA metabolism after aspirin treatment. MCF-7 and MDA-MB-468 human BC cell lines were transfected with siRNA to downregulate DDIT4. The expression of carnitine palmitoyltransferase 1 A (CPT1A) and serine 79-phosphorylated acetyl-CoA carboxylase 1 (ACC1) were analyzed by Western Blotting. Aspirin enhanced ACC1 phosphorylation by two-fold in MCF-7 cells and had no effect in MDA-MB-468 cells. Aspirin did not change the expression of CPT1A in either cell line. We have recently reported DDIT4 itself to be upregulated by aspirin. DDIT4 knockdown resulted in 1.5-fold decreased ACC1 phosphorylation (dephosphorylation activates the enzyme), 2-fold increased CPT1A expression in MCF-7 cells, and 2.8-fold reduced phosphorylation of ACC1 following aspirin exposure in MDA-MB-468 cells. Thus, DDIT4 downregulation raised the activity of main lipid metabolism enzymes upon aspirin exposure which is an undesired effect as FA synthesis and oxidation are linked to malignant phenotype. This finding may be clinically relevant as DDIT4 expression has been shown to vary in breast tumors. Our findings justify further, more extensive investigation of the role of DDIT4 in aspirin’s effect on fatty acid metabolism in BC cells. Full article

(This article belongs to the Special Issue Advanced Molecular Solutions for Cancer Therapy)

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17 pages, 4530 KiB

Open AccessArticle

Metabolic Silencing via Methionine-Based Amino Acid Restriction in Head and Neck Cancer

by Anna Chiara Wünsch, Elena Ries, Sina Heinzelmann, Andrea Frabschka, Peter Christoph Wagner, Theresa Rauch, Corinna Koderer, Mohamed El-Mesery, Julian Manuel Volland, Alexander Christian Kübler, Stefan Hartmann and Axel Seher

Curr. Issues Mol. Biol. 2023, 45(6), 4557-4573; https://doi.org/10.3390/cimb45060289 - 24 May 2023

Cited by 1 | Viewed by 1850

Abstract

In recent years, various forms of caloric restriction (CR) and amino acid or protein restriction (AAR or PR) have shown not only success in preventing age-associated diseases, such as type II diabetes and cardiovascular diseases, but also potential for cancer therapy. These strategies [...] Read more.

In recent years, various forms of caloric restriction (CR) and amino acid or protein restriction (AAR or PR) have shown not only success in preventing age-associated diseases, such as type II diabetes and cardiovascular diseases, but also potential for cancer therapy. These strategies not only reprogram metabolism to low-energy metabolism (LEM), which is disadvantageous for neoplastic cells, but also significantly inhibit proliferation. Head and neck squamous cell carcinoma (HNSCC) is one of the most common tumour types, with over 600,000 new cases diagnosed annually worldwide. With a 5-year survival rate of approximately 55%, the poor prognosis has not improved despite extensive research and new adjuvant therapies. Therefore, for the first time, we analysed the potential of methionine restriction (MetR) in selected HNSCC cell lines. We investigated the influence of MetR on cell proliferation and vitality, the compensation for MetR by homocysteine, the gene regulation of different amino acid transporters, and the influence of cisplatin on cell proliferation in different HNSCC cell lines. Full article

(This article belongs to the Special Issue Advanced Molecular Solutions for Cancer Therapy)

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16 pages, 832 KiB

Open AccessArticle

Significant Association of Estrogen Receptor-β Isoforms and Coactivators in Breast Cancer Subtypes

by Young Choi and Simcha Pollack

Curr. Issues Mol. Biol. 2023, 45(3), 2533-2548; https://doi.org/10.3390/cimb45030166 - 17 Mar 2023

Viewed by 1895

Abstract

Nuclear receptor coregulators are the principal regulators of Estrogen Receptor (ER)-mediated transcription. ERβ, an ER subtype first identified in 1996, is associated with poor outcomes in breast cancer (BCa) subtypes, and the coexpression of the ERβ1 isoform and AIB-1 and TIF-2 coactivators in [...] Read more.

Nuclear receptor coregulators are the principal regulators of Estrogen Receptor (ER)-mediated transcription. ERβ, an ER subtype first identified in 1996, is associated with poor outcomes in breast cancer (BCa) subtypes, and the coexpression of the ERβ1 isoform and AIB-1 and TIF-2 coactivators in BCa-associated myofibroblasts is associated with high-grade BCa. We aimed to identify the specific coactivators that are involved in the progression of ERβ-expressing BCa. ERβ isoforms, coactivators, and prognostic markers were tested using standard immunohistochemistry. AIB-1, TIF-2, NF-kB, p-c-Jun, and/or cyclin D1 were differentially correlated with ERβ isoform expression in the BCa subtypes and subgroups. The coexpression of the ERβ5 and/or ERβ1 isoforms and the coactivators were found to be correlated with a high expression of P53, Ki-67, and Her2/neu and large-sized and/or high-grade tumors in BCa. Our study supports the notion that ERβ isoforms and coactivators seemingly coregulate the proliferation and progression of BCa and may provide insight into the potential therapeutic uses of the coactivators in BCa. Full article

(This article belongs to the Special Issue Advanced Molecular Solutions for Cancer Therapy)

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Review

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15 pages, 4846 KiB

Open AccessReview

Molecular Profiling of Circulating Tumour Cells and Circulating Tumour DNA: Complementary Insights from a Single Blood Sample Utilising the Parsortix^® System

by Gabrielle Wishart, Amy Templeman, Francesca Hendry, Karen Miller and Anne-Sophie Pailhes-Jimenez

Curr. Issues Mol. Biol. 2024, 46(1), 773-787; https://doi.org/10.3390/cimb46010050 - 17 Jan 2024

Cited by 4 | Viewed by 2349

Abstract

The study of molecular drivers of cancer is an area of rapid growth and has led to the development of targeted treatments, significantly improving patient outcomes in many cancer types. The identification of actionable mutations informing targeted treatment strategies are now considered essential [...] Read more.

The study of molecular drivers of cancer is an area of rapid growth and has led to the development of targeted treatments, significantly improving patient outcomes in many cancer types. The identification of actionable mutations informing targeted treatment strategies are now considered essential to the management of cancer. Traditionally, this information has been obtained through biomarker assessment of a tissue biopsy which is costly and can be associated with clinical complications and adverse events. In the last decade, blood-based liquid biopsy has emerged as a minimally invasive, fast, and cost-effective alternative, which is better suited to the requirement for longitudinal monitoring. Liquid biopsies allow for the concurrent study of multiple analytes, such as circulating tumour cells (CTCs) and circulating tumour DNA (ctDNA), from a single blood sample. Although ctDNA assays are commercially more advanced, there is an increasing awareness of the clinical significance of the transcriptome and proteome which can be analysed using CTCs. Herein, we review the literature in which the microfluidic, label-free Parsortix^® system is utilised for CTC capture, harvest and analysis, alongside the analysis of ctDNA from a single blood sample. This detailed summary of the literature demonstrates how these two analytes can provide complementary disease information. Full article

(This article belongs to the Special Issue Advanced Molecular Solutions for Cancer Therapy)

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28 pages, 12633 KiB

Open AccessReview

Clinical Significance of SOX10 Expression in Human Pathology

by Hisham F. Bahmad, Aran Thiravialingam, Karthik Sriganeshan, Jeffrey Gonzalez, Veronica Alvarez, Stephanie Ocejo, Alvaro R. Abreu, Rima Avellan, Alejandro H. Arzola, Sana Hachem and Robert Poppiti

Curr. Issues Mol. Biol. 2023, 45(12), 10131-10158; https://doi.org/10.3390/cimb45120633 - 15 Dec 2023

Cited by 5 | Viewed by 3777

Abstract

The embryonic development of neural crest cells and subsequent tissue differentiation are intricately regulated by specific transcription factors. Among these, SOX10, a member of the SOX gene family, stands out. Located on chromosome 22q13, the SOX10 gene encodes a transcription factor crucial [...] Read more.

The embryonic development of neural crest cells and subsequent tissue differentiation are intricately regulated by specific transcription factors. Among these, SOX10, a member of the SOX gene family, stands out. Located on chromosome 22q13, the SOX10 gene encodes a transcription factor crucial for the differentiation, migration, and maintenance of tissues derived from neural crest cells. It plays a pivotal role in developing various tissues, including the central and peripheral nervous systems, melanocytes, chondrocytes, and odontoblasts. Mutations in SOX10 have been associated with congenital disorders such as Waardenburg–Shah Syndrome, PCWH syndrome, and Kallman syndrome, underscoring its clinical significance. Furthermore, SOX10 is implicated in neural and neuroectodermal tumors, such as melanoma, malignant peripheral nerve sheath tumors (MPNSTs), and schwannomas, influencing processes like proliferation, migration, and differentiation. In mesenchymal tumors, SOX10 expression serves as a valuable marker for distinguishing between different tumor types. Additionally, SOX10 has been identified in various epithelial neoplasms, including breast, ovarian, salivary gland, nasopharyngeal, and bladder cancers, presenting itself as a potential diagnostic and prognostic marker. However, despite these associations, further research is imperative to elucidate its precise role in these malignancies. Full article

(This article belongs to the Special Issue Advanced Molecular Solutions for Cancer Therapy)

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26 pages, 1029 KiB

Open AccessReview

miRNA Expression Profiling in Human Breast Cancer Diagnostics and Therapy

by Iga Dziechciowska, Małgorzata Dąbrowska, Anna Mizielska, Natalia Pyra, Natalia Lisiak, Przemysław Kopczyński, Magdalena Jankowska-Wajda and Błażej Rubiś

Curr. Issues Mol. Biol. 2023, 45(12), 9500-9525; https://doi.org/10.3390/cimb45120595 - 25 Nov 2023

Cited by 4 | Viewed by 2182

Abstract

Breast cancer is one of the most commonly diagnosed cancer types worldwide. Regarding molecular characteristics and classification, it is a heterogeneous disease, which makes it more challenging to diagnose. As is commonly known, early detection plays a pivotal role in decreasing mortality and [...] Read more.

Breast cancer is one of the most commonly diagnosed cancer types worldwide. Regarding molecular characteristics and classification, it is a heterogeneous disease, which makes it more challenging to diagnose. As is commonly known, early detection plays a pivotal role in decreasing mortality and providing a better prognosis for all patients. Different treatment strategies can be adjusted based on tumor progression and molecular characteristics, including personalized therapies. However, dealing with resistance to drugs and recurrence is a challenge. The therapeutic options are limited and can still lead to poor clinical outcomes. This review aims to shed light on the current perspective on the role of miRNAs in breast cancer diagnostics, characteristics, and prognosis. We discuss the potential role of selected non-coding RNAs most commonly associated with breast cancer. These include miR-21, miR-106a, miR-155, miR-141, let-7c, miR-335, miR-126, miR-199a, miR-101, and miR-9, which are perceived as potential biomarkers in breast cancer prognosis, diagnostics, and treatment response monitoring. As miRNAs differ in expression levels in different types of cancer, they may provide novel cancer therapy strategies. However, some limitations regarding dynamic alterations, tissue-specific profiles, and detection methods must also be raised. Full article

(This article belongs to the Special Issue Advanced Molecular Solutions for Cancer Therapy)

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22 pages, 2465 KiB

Open AccessReview

Interaction and Collaboration of SP1, HIF-1, and MYC in Regulating the Expression of Cancer-Related Genes to Further Enhance Anticancer Drug Development

by Kotohiko Kimura, Tiffany L. B. Jackson and Ru Chih C. Huang

Curr. Issues Mol. Biol. 2023, 45(11), 9262-9283; https://doi.org/10.3390/cimb45110580 - 17 Nov 2023

Cited by 8 | Viewed by 3125

Abstract

Specificity protein 1 (SP1), hypoxia-inducible factor 1 (HIF-1), and MYC are important transcription factors (TFs). SP1, a constitutively expressed housekeeping gene, regulates diverse yet distinct biological activities; MYC is a master regulator of all key cellular activities including cell metabolism and proliferation; and [...] Read more.

Specificity protein 1 (SP1), hypoxia-inducible factor 1 (HIF-1), and MYC are important transcription factors (TFs). SP1, a constitutively expressed housekeeping gene, regulates diverse yet distinct biological activities; MYC is a master regulator of all key cellular activities including cell metabolism and proliferation; and HIF-1, whose protein level is rapidly increased when the local tissue oxygen concentration decreases, functions as a mediator of hypoxic signals. Systems analyses of the regulatory networks in cancer have shown that SP1, HIF-1, and MYC belong to a group of TFs that function as master regulators of cancer. Therefore, the contributions of these TFs are crucial to the development of cancer. SP1, HIF-1, and MYC are often overexpressed in tumors, which indicates the importance of their roles in the development of cancer. Thus, proper manipulation of SP1, HIF-1, and MYC by appropriate agents could have a strong negative impact on cancer development. Under these circumstances, these TFs have naturally become major targets for anticancer drug development. Accordingly, there are currently many SP1 or HIF-1 inhibitors available; however, designing efficient MYC inhibitors has been extremely difficult. Studies have shown that SP1, HIF-1, and MYC modulate the expression of each other and collaborate to regulate the expression of numerous genes. In this review, we provide an overview of the interactions and collaborations of SP1, HIF1A, and MYC in the regulation of various cancer-related genes, and their potential implications in the development of anticancer therapy. Full article

(This article belongs to the Special Issue Advanced Molecular Solutions for Cancer Therapy)

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18 pages, 1336 KiB

Open AccessReview

The Potential of Dendritic Cell Subsets in the Development of Personalized Immunotherapy for Cancer Treatment

by Anna Valerevna Gorodilova, Kristina Viktorovna Kitaeva, Ivan Yurevich Filin, Yuri Pavlovich Mayasin, Chulpan Bulatovna Kharisova, Shaza S. Issa, Valeriya Vladimirovna Solovyeva and Albert Anatolyevich Rizvanov

Curr. Issues Mol. Biol. 2023, 45(10), 8053-8070; https://doi.org/10.3390/cimb45100509 - 1 Oct 2023

Cited by 2 | Viewed by 2807

Abstract

Since the discovery of dendritic cells (DCs) in 1973 by Ralph Steinman, a tremendous amount of knowledge regarding these innate immunity cells has been accumulating. Their role in regulating both innate and adaptive immune processes is gradually being uncovered. DCs are proficient antigen-presenting [...] Read more.

Since the discovery of dendritic cells (DCs) in 1973 by Ralph Steinman, a tremendous amount of knowledge regarding these innate immunity cells has been accumulating. Their role in regulating both innate and adaptive immune processes is gradually being uncovered. DCs are proficient antigen-presenting cells capable of activating naive T-lymphocytes to initiate and generate effective anti-tumor responses. Although DC-based immunotherapy has not yielded significant results, the substantial number of ongoing clinical trials underscores the relevance of DC vaccines, particularly as adjunctive therapy or in combination with other treatment options. This review presents an overview of current knowledge regarding human DCs, their classification, and the functions of distinct DC populations. The stepwise process of developing therapeutic DC vaccines to treat oncological diseases is discussed, along with speculation on the potential of combined therapy approaches and the role of DC vaccines in modern immunotherapy. Full article

(This article belongs to the Special Issue Advanced Molecular Solutions for Cancer Therapy)

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25 pages, 769 KiB

Open AccessReview

The Role of Amino Acids in the Diagnosis, Risk Assessment, and Treatment of Breast Cancer: A Review

by Lyudmila V. Bel’skaya, Ivan A. Gundyrev and Denis V. Solomatin

Curr. Issues Mol. Biol. 2023, 45(9), 7513-7537; https://doi.org/10.3390/cimb45090474 - 13 Sep 2023

Cited by 4 | Viewed by 3193

Abstract

This review summarizes the role of amino acids in the diagnosis, risk assessment, imaging, and treatment of breast cancer. It was shown that the content of individual amino acids changes in breast cancer by an average of 10–15% compared with healthy controls. For [...] Read more.

This review summarizes the role of amino acids in the diagnosis, risk assessment, imaging, and treatment of breast cancer. It was shown that the content of individual amino acids changes in breast cancer by an average of 10–15% compared with healthy controls. For some amino acids (Thr, Arg, Met, and Ser), an increase in concentration is more often observed in breast cancer, and for others, a decrease is observed (Asp, Pro, Trp, and His). The accuracy of diagnostics using individual amino acids is low and increases when a number of amino acids are combined with each other or with other metabolites. Gln/Glu, Asp, Arg, Leu/Ile, Lys, and Orn have the greatest significance in assessing the risk of breast cancer. The variability in the amino acid composition of biological fluids was shown to depend on the breast cancer phenotype, as well as the age, race, and menopausal status of patients. In general, the analysis of changes in the amino acid metabolism in breast cancer is a promising strategy not only for diagnosis, but also for developing new therapeutic agents, monitoring the treatment process, correcting complications after treatment, and evaluating survival rates. Full article

(This article belongs to the Special Issue Advanced Molecular Solutions for Cancer Therapy)

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14 pages, 1570 KiB

Open AccessReview

Repurposing of the Drug Tezosentan for Cancer Therapy

by Eduarda Ribeiro and Nuno Vale

Curr. Issues Mol. Biol. 2023, 45(6), 5118-5131; https://doi.org/10.3390/cimb45060325 - 11 Jun 2023

Cited by 5 | Viewed by 2444

Abstract

Tezosentan is a vasodilator drug that was originally developed to treat pulmonary arterial hypertension. It acts by inhibiting endothelin (ET) receptors, which are overexpressed in many types of cancer cells. Endothelin-1 (ET1) is a substance produced by the body that causes blood vessels [...] Read more.

Tezosentan is a vasodilator drug that was originally developed to treat pulmonary arterial hypertension. It acts by inhibiting endothelin (ET) receptors, which are overexpressed in many types of cancer cells. Endothelin-1 (ET1) is a substance produced by the body that causes blood vessels to narrow. Tezosentan has affinity for both ET_A and ET_B receptors. By blocking the effects of ET1, tezosentan can help to dilate blood vessels, improve the blood flow, and reduce the workload on the heart. Tezosentan has been found to have anticancer properties due to its ability to target the ET receptors, which are involved in promoting cellular processes such as proliferation, survival, neovascularization, immune cell response, and drug resistance. This review intends to demonstrate the potential of this drug in the field of oncology. Drug repurposing can be an excellent way to improve the known profiles of first-line drugs and to solve several resistance problems of these same antineoplastic drugs. Full article

(This article belongs to the Special Issue Advanced Molecular Solutions for Cancer Therapy)

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15 pages, 1990 KiB

Open AccessReview

Adenovirus as a Vector and Oncolytic Virus

by Wataru Matsunaga and Akinobu Gotoh

Curr. Issues Mol. Biol. 2023, 45(6), 4826-4840; https://doi.org/10.3390/cimb45060307 - 2 Jun 2023

Cited by 12 | Viewed by 4128

Abstract

Adenoviral vectors, both oncolytic viruses and gene delivery vectors, are among the earliest approved and commercialised vectors for gene therapy. Adenoviruses have high cytotoxicity and immunogenicity. Therefore, lentiviruses or adeno-associated viruses as viral vectors and herpes simplex virus as an oncolytic virus have [...] Read more.

Adenoviral vectors, both oncolytic viruses and gene delivery vectors, are among the earliest approved and commercialised vectors for gene therapy. Adenoviruses have high cytotoxicity and immunogenicity. Therefore, lentiviruses or adeno-associated viruses as viral vectors and herpes simplex virus as an oncolytic virus have recently drawn attention. Thus, adenoviral vectors are often considered relatively obsolete. However, their high cargo limit and transduction efficiency are significant advantages over newer viral vectors. This review provides an overview of the new-generation adenoviral vectors. In addition, we describe the modification of the fiber knob region that enhances affinity of adenoviral vectors for cancer cells and the utilisation of cancer-cell-specific promoters to suppress expression of unwanted transgenes in non-malignant tissues. Full article

(This article belongs to the Special Issue Advanced Molecular Solutions for Cancer Therapy)

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15 pages, 753 KiB

Open AccessReview

Clinical Characteristics of Molecularly Defined Renal Cell Carcinomas

by Xinfeng Hu, Congzhu Tan and Guodong Zhu

Curr. Issues Mol. Biol. 2023, 45(6), 4763-4777; https://doi.org/10.3390/cimb45060303 - 31 May 2023

Cited by 2 | Viewed by 2717

Abstract

Kidney tumors comprise a broad spectrum of different histopathological entities, with more than 0.4 million newly diagnosed cases each year, mostly in middle-aged and older men. Based on the description of the 2022 World Health Organization (WHO) classification of renal cell carcinoma (RCC), [...] Read more.

Kidney tumors comprise a broad spectrum of different histopathological entities, with more than 0.4 million newly diagnosed cases each year, mostly in middle-aged and older men. Based on the description of the 2022 World Health Organization (WHO) classification of renal cell carcinoma (RCC), some new categories of tumor types have been added according to their specific molecular typing. However, studies on these types of RCC are still superficial, many types of these RCC currently lack accurate diagnostic standards in the clinic, and treatment protocols are largely consistent with the treatment guidelines for clear cell RCC (ccRCC), which might result in worse treatment outcomes for patients with these types of molecularly defined RCC. In this article, we conduct a narrative review of the literature published in the last 15 years on molecularly defined RCC. The purpose of this review is to summarize the clinical features and the current status of research on the detection and treatment of molecularly defined RCC. Full article

(This article belongs to the Special Issue Advanced Molecular Solutions for Cancer Therapy)

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Other

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9 pages, 5475 KiB

Open AccessCase Report

The Case of an Endometrial Cancer Patient with Breast Cancer Who Has Achieved Long-Term Survival via Letrozole Monotherapy

by Masako Ishikawa, Kentaro Nakayama, Sultana Razia, Hitomi Yamashita, Tomoka Ishibashi, Hikaru Haraga, Kosuke Kanno, Noriyoshi Ishikawa and Satoru Kyo

Curr. Issues Mol. Biol. 2023, 45(4), 2908-2916; https://doi.org/10.3390/cimb45040190 - 1 Apr 2023

Cited by 2 | Viewed by 2332

Abstract

Herein, we present the successful treatment of a 92-year-old woman who experienced recurrent EC in the vaginal stump and para-aortic lymph nodes. The patient was first treated with paclitaxel and carboplatin for recurrent EC, which was abandoned after two cycles of chemotherapy because [...] Read more.

Herein, we present the successful treatment of a 92-year-old woman who experienced recurrent EC in the vaginal stump and para-aortic lymph nodes. The patient was first treated with paclitaxel and carboplatin for recurrent EC, which was abandoned after two cycles of chemotherapy because of G4 hematologic toxicity. Later, the patient was treated with letrozole for early-stage breast cancer, which was diagnosed simultaneously with EC recurrence. After four months of hormonal therapy, a partial response was observed not only in the lesions in the breast, but also those in the vaginal stump and para-aortic lymph nodes. She had no recurrence of breast cancer or EC, even after six years of treatment with letrozole-based hormonal therapy. Subsequent whole-exome sequencing using the genomic DNA isolated from the surgical specimen in the uterine tumor identified several genetic variants, including actionable mutations, such as CTNNB1 (p.S37F), PIK3R1 (p.M582Is_10), and TP53 c.375 + 5G>T. These data suggest that the efficacy of letrozole is mediated by blocking the mammalian target of the rapamycin pathway. The findings of this study, substantiated via genetic analysis, suggest the possibility of long-term disease-free survival, even in elderly patients with recurrent EC, which was thought to be difficult to cure completely. Full article

(This article belongs to the Special Issue Advanced Molecular Solutions for Cancer Therapy)

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