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Cancers
Special Issues
Mechanisms of Therapy Resistance in Cancers
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Mechanisms of Therapy Resistance in Cancers

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Drug Development".

Deadline for manuscript submissions: 31 May 2024 | Viewed by 2580

Special Issue Editor

Dr. Birandra K Sinha

E-Mail Website
Guest Editor
Laboratory of Toxicology and Toxicokinetic, National Cancer Institute at National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
Interests: oxidative stress; nitric oxide; topoisomerases; pharmacology of anticancer drugs; mechanism of drug resistance

Special Issue Information

Dear Colleagues,

Cancer is one of the leading causes of death in the US and across the world. The current management techniques for cancers include cytoreductive surgery, chemotherapy, targeted therapy, radiation therapy, endocrine therapy and immunotherapy. Despite the significant success achieved in treating cancers over the past few decades, the development of resistance to cytotoxic chemotherapeutic agents and/or novel targeted drugs continues to be a major problem in cancer therapies. Drug resistance, either before treatment (intrinsic) or following therapy (acquired), is responsible for most relapses of cancer and death. Cancer therapeutic resistance occurs as cancer cells develop resistance to therapy through various mechanisms, including (a) alterations and or mutations of drug targets, e.g., topoisomerases; (b) overexpression of ABC-dependent transporter proteins, e.g., P-glycoprotein 170; (c) enhanced expression of detoxification proteins, e.g., SOD, and (d) enhanced expression of DNA damage repair proteins. Therapeutic failure cannot be an option, and we need to understand the dynamics of tumor adaptation in order to adequately adjust therapies. Therefore, a clear understanding of the mechanisms of drug resistance is essential to provide future guidance to successful treatment and achieve better outcomes.  In this Special Issue, new discoveries in the mechanisms of drug resistance will be discussed. Particularly, we will highlight the roles of ATP-dependent transporters in multi-drug resistance, as well as the roles of enhanced detoxification in drug resistance. Furthermore, novel and emerging roles of resistance to immunotherapy will be emphasized. The complexity of the development of drug resistance indicates that combinational and personalized therapies might provide better strategies and improved efficacy for fighting drug resistance in clinics.

Dr. Birandra K Sinha
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. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). 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

  • ATP-binding cassette transporters
  • cancer stem cells
  • extracellular ATP
  • repair of DNA damage
  • immunotherapy resistance

Published Papers (2 papers)

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Research

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13 pages, 19031 KiB  
Article
SIRT1 Promotes Cisplatin Resistance in Bladder Cancer via Beclin1 Deacetylation-Mediated Autophagy
by Yan Sun, Xudong Liu, Hang Tong, Hubin Yin, Tinghao Li, Junlong Zhu, Junrui Chen, Linfeng Wu, Xiaoyu Zhang, Xin Gou and Weiyang He
Cancers 2024, 16(1), 125; https://doi.org/10.3390/cancers16010125 - 26 Dec 2023
Cited by 1 | Viewed by 788
Abstract
Autophagy-dependent cisplatin resistance poses a challenge in bladder cancer treatment. SIRT1, a protein deacetylase, is involved in autophagy regulation. However, the precise mechanism through which SIRT1 mediates cisplatin resistance in bladder cancer via autophagy remains unclear. In this study, we developed a cisplatin-resistant [...] Read more.
Autophagy-dependent cisplatin resistance poses a challenge in bladder cancer treatment. SIRT1, a protein deacetylase, is involved in autophagy regulation. However, the precise mechanism through which SIRT1 mediates cisplatin resistance in bladder cancer via autophagy remains unclear. In this study, we developed a cisplatin-resistant T24/DDP cell line to investigate this mechanism. The apoptosis rate and cell viability were assessed using flow cytometry and the CCK8 method. The expression levels of the relevant RNA and protein were determined using RT-qPCR and a Western blot analysis, respectively. Immunoprecipitation was utilized to validate the interaction between SIRT1 and Beclin1, as well as to determine the acetylation level of Beclin1. The findings indicated the successful construction of the T24/DDP cell line, which exhibited autophagy-dependent cisplatin resistance. Inhibiting autophagy significantly reduced the drug resistance index of these cells. The T24/DDP cell line showed a high SIRT1 expression level. The overexpression of SIRT1 activated autophagy, thereby further promoting cisplatin resistance in the T24/DDP cell line. Conversely, inhibiting autophagy counteracted the cisplatin-resistance-promoting effects of SIRT1. Silencing SIRT1 led to increased acetylation of Beclin1, the inhibition of autophagy, and a reduction in the cisplatin resistance of the T24/DDP cell line. Introducing a double mutation (lysine 430 and 437 to arginine, 2KR) in Beclin-1 inhibited acetylation and activated autophagy, effectively reversing the decreased cisplatin resistance resulting from SIRT1 silencing. In summary, our study elucidated that SIRT1 promotes cisplatin resistance in human bladder cancer T24 cells through Beclin1-deacetylation-mediated autophagy activation. These findings suggest a potential new strategy for reversing cisplatin resistance in bladder cancer. Full article
(This article belongs to the Special Issue Mechanisms of Therapy Resistance in Cancers)
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Review

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32 pages, 2957 KiB  
Review
Understanding Cancer’s Defense against Topoisomerase-Active Drugs: A Comprehensive Review
by Nilesh Kumar Sharma, Anjali Bahot, Gopinath Sekar, Mahima Bansode, Kratika Khunteta, Priyanka Vijay Sonar, Ameya Hebale, Vaishnavi Salokhe and Birandra Kumar Sinha
Cancers 2024, 16(4), 680; https://doi.org/10.3390/cancers16040680 - 06 Feb 2024
Cited by 2 | Viewed by 1440
Abstract
In recent years, the emergence of cancer drug resistance has been one of the crucial tumor hallmarks that are supported by the level of genetic heterogeneity and complexities at cellular levels. Oxidative stress, immune evasion, metabolic reprogramming, overexpression of ABC transporters, and stemness [...] Read more.
In recent years, the emergence of cancer drug resistance has been one of the crucial tumor hallmarks that are supported by the level of genetic heterogeneity and complexities at cellular levels. Oxidative stress, immune evasion, metabolic reprogramming, overexpression of ABC transporters, and stemness are among the several key contributing molecular and cellular response mechanisms. Topo-active drugs, e.g., doxorubicin and topotecan, are clinically active and are utilized extensively against a wide variety of human tumors and often result in the development of resistance and failure to therapy. Thus, there is an urgent need for an incremental and comprehensive understanding of mechanisms of cancer drug resistance specifically in the context of topo-active drugs. This review delves into the intricate mechanistic aspects of these intracellular and extracellular topo-active drug resistance mechanisms and explores the use of potential combinatorial approaches by utilizing various topo-active drugs and inhibitors of pathways involved in drug resistance. We believe that this review will help guide basic scientists, pre-clinicians, clinicians, and policymakers toward holistic and interdisciplinary strategies that transcend resistance, renewing optimism in the ongoing battle against cancer. Full article
(This article belongs to the Special Issue Mechanisms of Therapy Resistance in Cancers)
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