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Molecular Biology and Drug-Resistance of Cancer Cells

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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 (30 July 2023) | Viewed by 8615

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Special Issue Editor

Dr. Kausik Bishayee

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Guest Editor

Biomedical Science Core-Facility, Soonchunhyang Institute of Medi-bio Science, Soonchunhyang University, Cheonan 31151, Korea
Interests: oncology; signaling pathways; metabolism; RNA binding proteins; mTORC1; cancer cell biology; pharmacology; neurotoxicity; neocortex development; autophagy

Special Issue Information

Dear Colleagues,

Cancer cells are intelligent, highly proliferative, genetically unstable, and resistant to stress. Cancer cells usually modify themselves genetically to protect themselves from extracellular stresses, which induces drug resistance. The development of drug resistance often causes therapeutic difficulty in cancer patients as several mutations or genetic rearrangements can feed into the drug resistance mechanism. Cancer cells alter various molecular pathways, including disabling the drug targets and receptors, inhibiting cell death pathways, adjusting the drug metabolism, and inducing epigenetic modifications.

Novel anticancer therapies may be developed by considering the following factors,

Constant monitoring of the drug resistance behavior, which is required to identify genetic alterations in cancer cells;
Identification of the molecular mechanism of drug resistance and targeted therapy protocol against specific genes;
Sensitization of cancer cells to chemotherapeutic agents through targeted RNAi practice (miRNA or siRNA) against drug resistance genes;
Implementation of combination therapy for drug-resistant cancer types, as drug cocktails often produce synergistic or additive effects against drug-resistant cancers;
Metabolic monitoring and metabolic pathway targeted therapy (e.g., Warburg pathway, OXPHOS pathway), which are required to overcome the metabolic alterations and escapes of the cancer cells;
Development of novel synthetic drugs with more profound responses by integrating clinical-genomic data and computational modeling systems.

The knowledge of the molecular mechanism of drug resistance in cancer is limited and must thoroughly be investigated. This research topic will redefine our approach to understanding the molecular mechanism of developing drug resistance in cancer cells.

Dr. Kausik Bishayee
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

cancer cells
stress-resistant
drug-resistant
signaling pathway
molecular mechanism of drug action
oncogenes
cell death
metabolic alteration
epigenetic modification

Published Papers (4 papers)

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Research

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12 pages, 2361 KiB

Open AccessArticle

The Response of Triple-Negative Breast Cancer to Neoadjuvant Chemotherapy and the Epithelial–Mesenchymal Transition

by Stefano Zapperi and Caterina A. M. La Porta

Int. J. Mol. Sci. 2023, 24(7), 6422; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24076422 - 29 Mar 2023

Cited by 1 | Viewed by 2210

Abstract

It would be highly desirable to find prognostic and predictive markers for triple-negative breast cancer (TNBC), a strongly heterogeneous and invasive breast cancer subtype often characterized by a high recurrence rate and a poor outcome. Here, we investigated the prognostic and predictive capabilities of ARIADNE, a recently developed transcriptomic test focusing on the epithelial–mesenchymal transition. We first compared the stratification of TNBC patients obtained by ARIADNE with that based on other common pathological indicators, such as grade, stage and nodal status, and found that ARIADNE was more effective than the other methods in dividing patients into groups with different disease-free survival statistics. Next, we considered the response to neoadjuvant chemotherapy and found that the classification provided by ARIADNE led to statistically significant differences in the rates of pathological complete response within the groups. Full article

(This article belongs to the Special Issue Molecular Biology and Drug-Resistance of Cancer Cells)

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15 pages, 2431 KiB

Open AccessArticle

Investigation of Molecular Mechanisms Involved in Sensitivity to the Anti-Cancer Activity of Costunolide in Breast Cancer Cells

by Yu-Jeong Choi, Youn Kyung Choi, Seong-Gyu Ko, Chunhoo Cheon and Tai Young Kim

Int. J. Mol. Sci. 2023, 24(4), 4009; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24044009 - 16 Feb 2023

Cited by 4 | Viewed by 1733

Abstract

Costunolide (CTL), an active compound isolated from Saussurea lappa Clarke and Laurus nobilis L, has been shown to induce apoptosis via reactive oxygen species (ROS) generation in various types of cancer cells. However, details of molecular mechanisms underlying the difference in sensitivity of cancer cells to CTL are still largely unknown. Here, we tested the effect of CTL on the viability of breast cancer cells and found that CTL had a more efficient cytotoxic effect against SK-BR-3 cells than MCF-7 cells. Mechanically, ROS levels were significantly increased upon CTL treatment only in SK-BR-3 cells, which leads to lysosomal membrane permeabilization (LMP) and cathepsin D release, and subsequent activation of the mitochondrial-dependent intrinsic apoptotic pathway by inducing mitochondrial outer membrane permeabilization (MOMP). In contrast, treatment of MCF-7 cells with CTL activated PINK1/Parkin-dependent mitophagy to remove damaged mitochondria, which prevented the elevation of ROS levels, thereby contributing to their reduced sensitivity to CTL. These results suggest that CTL is a potent anti-cancer agent, and its combination with the inhibition of mitophagy could be an effective method for treating breast cancer cells that are less sensitive to CTL. Full article

(This article belongs to the Special Issue Molecular Biology and Drug-Resistance of Cancer Cells)

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16 pages, 3942 KiB

Open AccessArticle

Endogenous Retrovirus RNA Expression Differences between Race, Stage and HPV Status Offer Improved Prognostication among Women with Cervical Cancer

by Jill Alldredge, Vinay Kumar, James Nguyen, Brooke E. Sanders, Karina Gomez, Kay Jayachandran, Jin Zhang, Julie Schwarz and Farah Rahmatpanah

Int. J. Mol. Sci. 2023, 24(2), 1492; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24021492 - 12 Jan 2023

Cited by 1 | Viewed by 1766

Abstract

Endogenous human retroviruses (ERVs) are remnants of exogenous retroviruses that have integrated into the human genome. Using publicly available RNA-seq data from 63 cervical cancer patients, we investigated the expression of ERVs in cervical cancers. Four aspects of cervical cancer were investigated: patient ancestral background, tumor HPV type, tumor stage and patient survival. Between the racial subgroups, 74 ERVs were significantly differentially expressed, with Black Americans having 30 upregulated and 44 downregulated (including MER21C, HERV9-int, and HERVH-int) ERVs when compared to White Americans. We found that 3313 ERVs were differentially expressed between HPV subgroups, including MER41A, HERVH-int and HERVK9. There were 28 downregulated (including MLT1D and HERVH-int) and 61 upregulated (including MER41A) ERVs in locally advanced-stage compared to early-stage samples. Tissue microarrays of cervical cancer patients were used to investigate the protein expression of ERVs with protein coding potential (i.e., HERVK and ERV3). Significant differences in protein expression of ERV3 (p = 0.000905) were observed between early-stage and locally advanced-stage tumors. No significant differential expression at the protein level was found for HERVK7 (p = 0.243). We also investigated a prognostic model, supplementing a baseline prediction model using FIGO stage, age and HPV positivity with ERVs data. The expression levels of all ERVs in the HERVd were input into a Lasso-Cox proportional hazards model, developing a predictive 67-ERV panel. When ERVs expression levels were supplemented with the clinical data, a significant increase in prognostic power (p = 9.433 × 10⁻¹⁵) relative to that obtained with the clinical parameters alone (p = 0.06027) was observed. In summary, ERV RNA expression in cervical cancer tumors is significantly different among racial cohorts, HPV subgroups and disease stages. The combination of the expression of certain ERVs in cervical cancers with clinical factors significantly improved prognostication compared to clinical factors alone; therefore, ERVs may serve as future prognostic biomarkers and therapeutic targets. Novelty and Impact: When endogenous retroviral (ERV) expression signatures were combined with currently employed clinical prognosticators of relapse of cervical cancer, the combination outperformed prediction models based on clinical prognosticators alone. ERV expression signatures in tumor biopsies may therefore be useful to help identify patients at greater risk of recurrence. The novel ERV expression signatures or adjacent genes possibly impacted by ERV expression described here may also be targets for the development of future therapeutic interventions. Full article

(This article belongs to the Special Issue Molecular Biology and Drug-Resistance of Cancer Cells)

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Review

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26 pages, 3062 KiB

Open AccessReview

The Illustration of Altered Glucose Dependency in Drug-Resistant Cancer Cells

by Kausik Bishayee, Seung-Hee Lee and Yong Soo Park

Int. J. Mol. Sci. 2023, 24(18), 13928; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms241813928 - 11 Sep 2023

Viewed by 2318

Abstract

A chemotherapeutic approach is crucial in malignancy management, which is often challenging due to the development of chemoresistance. Over time, chemo-resistant cancer cells rapidly repopulate and metastasize, increasing the recurrence rate in cancer patients. Targeting these destined cancer cells is more troublesome for clinicians, as they share biology and molecular cross-talks with normal cells. However, the recent insights into the metabolic profiles of chemo-resistant cancer cells surprisingly illustrated the activation of distinct pathways compared with chemo-sensitive or primary cancer cells. These distinct metabolic dynamics are vital and contribute to the shift from chemo-sensitivity to chemo-resistance in cancer. This review will discuss the important metabolic alterations in cancer cells that lead to drug resistance. Full article

(This article belongs to the Special Issue Molecular Biology and Drug-Resistance of Cancer Cells)

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