The paradigm of drug resistance in cancer: an epigenetic perspective

Adhikari, Swagata; Bhattacharya, Apoorva; Adhikary, Santanu; Singh, Vipin Kumar; Gadad, Shrikanth S.; Roy, Siddhartha; Das, Chandrima

doi:10.1042/bsr20211812

Cited by 37 publications

(21 citation statements)

References 313 publications

(220 reference statements)

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“…For decades, drug resistance towards the conventional therapeutic regimens has imposed a significant challenge for the successful management of cancer. Epigenetic modifications play a crucial role in the individual patient’s response to anticancer drugs and in drug resistance [ 146 ]. Based on the data presented here, Top I inhibitors are one of the major anticancer families affected by epigenetic alterations.…”

Section: Expert Opinionmentioning

confidence: 99%

Epigenetic modulations in cancer: predictive biomarkers and potential targets for overcoming the resistance to topoisomerase I inhibitors

et al. 2023

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Introduction Altered epigenetic map is frequently observed in cancer and recent investigations have demonstrated a pertinent role of epigenetic modifications in the response to many anticancer drugs including the DNA damaging agents. Topoisomerase I (Top I) is a well-known nuclear enzyme that is critical for DNA function and cell survival and its inhibition causes DNA strand breaks and cell cycle arrest. Inhibitors of human Top I have proven to be a prosperous chemotherapeutic treatment for a vast number of cancer patients. While the treatment is efficacious in many cases, resistance and altered cellular response remain major therapeutic issues. Areas covered This review highlights the evidence available till date on the influence of different epigenetic modifications on the response to Top I inhibitors as well as the implications of targeting epigenetic alterations for improving the efficacy and safety of Top I inhibitors. Expert opinion The field of epigenetic research is steadily growing. With its assistance, we could gain better understanding on how drug response and resistance work. Epigenetics can evolve as possible biomarkers and predictors of response to many medications including Top I inhibitors, and could have significant clinical implications that necessitate deeper attention. HIGHLIGHTS Epigenetic alterations, including DNA methylation and histone modifications, play a pertinent role in the response to several anticancer treatments, including DNA damaging agents like Top I inhibitors. Although camptothecin derivatives are used clinically as Top I inhibitors for management of cancer, certain types of cancer have inherent and or acquired resistance that limit the curative potential of them. Epigenetic modifications like DNA hypomethylation can either increase or decrease sensitivity to Top I inhibitors by different mechanisms. The combination of Top I inhibitors with the inhibitors of histone modifying enzymes can result in enhanced cytotoxic effects and sensitization of resistant cells to Top I inhibitors. MicroRNAs were found to directly influence the expression of Top I and other proteins in cancer cells resulting in positive or negative alteration of the response to Top I inhibitors. lncRNAs and their genetic polymorphisms have been found to be associated with Top I function and the response to its inhibitors. Clinical trials of epigenetic drugs in combination with Top I inhibitors are plentiful and some of them showed potentially promising outcomes.

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Section: Expert Opinionmentioning

confidence: 99%

Epigenetic modulations in cancer: predictive biomarkers and potential targets for overcoming the resistance to topoisomerase I inhibitors

et al. 2023

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“…Excessive drug efflux is considered a critical mechanism contributing to cancer drug resistance, in which the efficiency of anticancer drugs is significantly limited due to the reduction in drug concentration in cancer cells ( 150 ). It has been reported that excessive drug efflux is a result of the upregulation of drug efflux pumps, including ATP-binding cassette (ABC) transporters.…”

Section: Mechanisms Of Ncrnas In Mediating Cancer Drug Resistancementioning

confidence: 99%

Non-coding RNA in cancer drug resistance: Underlying mechanisms and clinical applications

Zhou

Jia

et al. 2022

Front. Oncol.

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Cancer is one of the most frequently diagnosed malignant diseases worldwide, posing a serious, long-term threat to patients’ health and life. Systemic chemotherapy remains the first-line therapeutic approach for recurrent or metastatic cancer patients after surgery, with the potential to effectively extend patient survival. However, the development of drug resistance seriously limits the clinical efficiency of chemotherapy and ultimately results in treatment failure and patient death. A large number of studies have shown that non-coding RNAs (ncRNAs), particularly microRNAs, long non-coding RNAs, and circular RNAs, are widely involved in the regulation of cancer drug resistance. Their dysregulation contributes to the development of cancer drug resistance by modulating the expression of specific target genes involved in cellular apoptosis, autophagy, drug efflux, epithelial-to-mesenchymal transition (EMT), and cancer stem cells (CSCs). Moreover, some ncRNAs also possess great potential as efficient, specific biomarkers in diagnosis and prognosis as well as therapeutic targets in cancer patients. In this review, we summarize the recent findings on the emerging role and underlying mechanisms of ncRNAs involved in cancer drug resistance and focus on their clinical applications as biomarkers and therapeutic targets in cancer treatment. This information will be of great benefit to early diagnosis and prognostic assessments of cancer as well as the development of ncRNA-based therapeutic strategies for cancer patients.

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“…Cancer is a highly prevalent and lethal global disease, second only to cardiovascular disease in terms of its impact 9 . Gastric cancer (GC) is a widespread malignancy, accounting for around 1,090,000 new instances and 770,000 fatalities in 2020 globally.…”

Section: Introductionmentioning

confidence: 99%

“…Cancer is a highly prevalent and lethal global disease, second only to cardiovascular disease in terms of its impact. 9 Gastric cancer (GC) is a widespread malignancy, accounting for around 1,090,000 new instances and 770,000 fatalities in 2020 globally. Based on these statistics, GC ranks as the fifth most prevalent cancer and is the fourth most common cause of cancer-related mortality.…”

Section: Introductionmentioning

confidence: 99%

Targeting ferroptosis in gastric cancer: Strategies and opportunities

Le,

Pan,

Zhang

et al. 2023

Immunological Reviews

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SummaryFerroptosis is a novel form of programmed cell death morphologically, genetically, and biochemically distinct from other cell death pathways and characterized by the accumulation of iron‐dependent lipid peroxides and oxidative damage. It is now understood that ferroptosis plays an essential role in various biological processes, especially in the metabolism of iron, lipids, and amino acids. Gastric cancer (GC) is a prevalent malignant tumor worldwide with low early diagnosis rates and high metastasis rates, accounting for its relatively poor prognosis. Although chemotherapy is commonly used to treat GC, drug resistance often leads to poor therapeutic outcomes. In the last several years, extensive research on ferroptosis has highlighted its significant potential in GC therapy, providing a promising strategy to address drug resistance associated with standard cancer therapies. In this review, we offer an extensive summary of the key regulatory factors related to the mechanisms underlying ferroptosis. Various inducers and inhibitors specifically targeting ferroptosis are uncovered. Additionally, we explore the prospective applications and outcomes of these agents in the field of GC therapy, emphasizing their capacity to improve the outcomes of this patient population.

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The paradigm of drug resistance in cancer: an epigenetic perspective

Cited by 37 publications

References 313 publications

Epigenetic modulations in cancer: predictive biomarkers and potential targets for overcoming the resistance to topoisomerase I inhibitors

Epigenetic modulations in cancer: predictive biomarkers and potential targets for overcoming the resistance to topoisomerase I inhibitors

Non-coding RNA in cancer drug resistance: Underlying mechanisms and clinical applications

Targeting ferroptosis in gastric cancer: Strategies and opportunities

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