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Combating Drug Resistance in Cancer: From Novel Biomarkers to Enhanced Therapeutic Efficacy—2nd Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (1 May 2024) | Viewed by 1741

Special Issue Editor


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Guest Editor
Centre for Applied Bioanthropology, Institute for Anthropological Research Ljudevita Gaja 32, 10000 Zagreb, Croatia
Interests: chemotherapy; chemoresistance; cancer biology; colon cancer; cell signaling; proteomics; lipidomics; sphingolipids; biomarkers; personalised medicine
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Special Issue Information

Dear Colleagues,

The development of chemoresistance represents a significant hurdle for successfully treating cancer. Many scientific findings from recent preclinical and clinical studies have undoubtedly broadened our current knowledge of the mechanisms underlying the development of cancer drug resistance, paving the way for the design of novel therapeutic strategies for patients with refractory cancer. In particular, numerous genomics studies have already been conducted in different cancer types to uncover the significant molecular players governing cancer progression and treatment response; these data are publicly available in various cancer databases and repositories. However, the more comprehensive characterisation of cancer drug resistance encompassing different layers of molecular information (e.g., transcriptomics, proteomics, metabolomics, lipidomics, microRNAs, long non-coding RNAs, medical/mass-spectrometry imaging, etc.), the integration and analysis of data from public cancer data repositories and newly obtained experimental data using artificial intelligence tools could facilitate the data-driven identification of crucial molecular features in chemoresistance. In addition, the discovery of novel biomarkers that could enable the monitoring of treatment response for timely identification of cancer patients with an increased risk of disease recurrence holds promise in improving the management of cancer patients. In this Special Issue of IJMS, we welcome basic and translational studies that address all issues pertinent to cancer drug resistance, including the following: the discovery of novel molecular mechanisms and druggable targets for chemoresistance; the identification of novel prognostic and predictive biomarkers of chemoresistance to enable patient stratification and tailored treatment; the application of bioinformatics and artificial intelligence tools for drug response prediction, risk stratification and the elucidation of chemoresistance mechanisms by integrating different molecular information; and the discovery of novel combinations of clinically approved anticancer drugs with chemotherapy-sensitising agents to overcome chemoresistance in cancer patients.

More published papers can be found in the closed Special Issue of our first edition: Combating Drug Resistance in Cancer—from Novel Biomarkers to Enhanced Therapeutic Efficacy.

Dr. Mirela Sedic
Guest Editor

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Keywords

  • chemoresistance
  • biomarker
  • artificial intelligence
  • bioinformatics
  • -omics
  • anti-cancer drug response prediction
  • risk stratification
  • rational cancer treatment combinations

Published Papers (1 paper)

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Research

25 pages, 10171 KiB  
Communication
Ezrin Inhibition Overcomes Acquired Resistance to Vemurafenib in BRAFV600E-Mutated Colon Cancer and Melanoma Cells In Vitro
by Iris Car, Antje Dittmann, Olga Vasieva, Luka Bočkor, Petra Grbčić, Nikolina Piteša, Marko Klobučar, Sandra Kraljević Pavelić and Mirela Sedić
Int. J. Mol. Sci. 2023, 24(16), 12906; https://doi.org/10.3390/ijms241612906 - 17 Aug 2023
Viewed by 1450
Abstract
Despite the advancements in targeted therapy for BRAFV600E-mutated metastatic colorectal cancer (mCRC), the development of resistance to BRAFV600E inhibition limits the response rate and durability of the treatment. Better understanding of the resistance mechanisms to BRAF inhibitors will facilitate the design of novel [...] Read more.
Despite the advancements in targeted therapy for BRAFV600E-mutated metastatic colorectal cancer (mCRC), the development of resistance to BRAFV600E inhibition limits the response rate and durability of the treatment. Better understanding of the resistance mechanisms to BRAF inhibitors will facilitate the design of novel pharmacological strategies for BRAF-mutated mCRC. The aim of this study was to identify novel protein candidates involved in acquired resistance to BRAFV600E inhibitor vemurafenib in BRAFV600E-mutated colon cancer cells using an integrated proteomics approach. Bioinformatic analysis of obtained proteomics data indicated actin-cytoskeleton linker protein ezrin as a highly ranked protein significantly associated with vemurafenib resistance whose overexpression in the resistant cells was additionally confirmed at the gene and protein level. Ezrin inhibition by NSC305787 increased anti-proliferative and pro-apoptotic effects of vemurafenib in the resistant cells in an additive manner, which was accompanied by downregulation of CD44 expression and inhibition of AKT/c-Myc activities. We also detected an increased ezrin expression in vemurafenib-resistant melanoma cells harbouring the BRAFV600E mutation. Importantly, ezrin inhibition potentiated anti-proliferative and pro-apoptotic effects of vemurafenib in the resistant melanoma cells in a synergistic manner. Altogether, our study suggests a role of ezrin in acquired resistance to vemurafenib in colon cancer and melanoma cells carrying the BRAFV600E mutation and supports further pre-clinical and clinical studies to explore the benefits of combined BRAF inhibitors and actin-targeting drugs as a potential therapeutic approach for BRAFV600E-mutated cancers. Full article
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