Cancer Drug Resistance in Innovative Strategies: A Scientific Review
M3 India Newsdesk Dec 27, 2024
This review article explores the latest advancements in approaches to combat cancer drug resistance, including combination therapies, targeted therapies, immunotherapy, and genetic editing technologies.
Cancer drug resistance presents a significant challenge in the treatment of malignancies, often leading to treatment failure and poor patient outcomes. Understanding the underlying mechanisms of resistance has led to the development of innovative strategies to overcome these obstacles.
Cancer remains one of the leading causes of morbidity and mortality worldwide, with the Global Cancer Observatory estimating approximately 19.3 million new cancer cases and 10 million cancer deaths in 2020. Despite the introduction of novel therapeutic agents, drug resistance continues to undermine treatment efficacy.
This phenomenon can be attributed to various factors, including genetic mutations, epigenetic modifications, tumour microenvironment interactions, and cancer stem cell properties [8]. This review aims to highlight innovative strategies being investigated to combat cancer drug resistance.
Mechanisms of drug resistance
1. Genetic alterations
Tumours can acquire drug resistance through mutations in target genes, such as KRAS, BRAF, and EGFR in various cancers [6]. These mutations can alter the drug's binding site, rendering the therapeutic agent ineffective.
2. Epigenetic changes
Epigenetic modifications can affect gene expression without altering the DNA sequence. Changes such as DNA methylation and histone modification may silence tumour suppressor genes or activate oncogenes, contributing to resistance [10].
3. Tumour microenvironment
The tumour microenvironment plays a crucial role in drug response. Components such as fibroblasts, immune cells, and extracellular matrix can alter drug distribution and effectiveness [4].
4. Cancer stem cells
Cancer stem cells (CSCs) are a subpopulation of cells within tumours that possess self-renewal capabilities and are often resistant to conventional therapies. Targeting CSCs has emerged as a potential strategy to overcome resistance [7].
Innovative strategies to overcome drug resistance
1. Combination therapies
Combining different therapeutic agents has been shown to enhance efficacy and overcome resistance. For example, combining targeted therapies with chemotherapy or immunotherapy can mitigate the development of resistance [9]. Clinical trials are ongoing to evaluate such combinations in various cancer types.
2. Targeted therapy
Targeted therapies exploit specific molecular alterations in tumours. New agents that target novel pathways or resistance mechanisms, such as BCL-2 inhibitors in acute myeloid leukaemia, are being developed. By precisely targeting the aberrant pathways, these therapies can effectively counteract drug resistance [5].
3. Immunotherapy
Cancer immunotherapy has revolutionised cancer treatment. Strategies such as checkpoint inhibitors, CAR-T cell therapy, and immune agonists seek to enhance the patient’s immune response against tumour cells. Research is investigating how to enhance the effectiveness of these therapies in resistant tumours [2].
4. Genetic editing technologies
Technological advancements such as CRISPR/Cas9 have opened avenues for directly editing genetic alterations responsible for drug resistance. By knocking out resistance genes or reintroducing tumour suppressors, researchers aim to restore sensitivity to treatment [3].
5. Epigenetic modulation
Agents that target epigenetic modifications are being evaluated for their ability to reverse drug resistance in cancer. By restoring normal expression patterns of tumour suppressor genes, these agents may sensitise resistant tumours to conventional therapies [1].
Cancer drug resistance remains a significant barrier to effective treatment; however, innovative strategies are continuously being developed to combat this challenge. Integrating combination therapies, targeted treatments, immunotherapy, genetic editing, and epigenetic modulation presents new prospects for overcoming drug resistance. Ongoing research is essential to refine these strategies and bring them from bench to bedside.
Disclaimer- The views and opinions expressed in this article are those of the author and do not necessarily reflect the official policy or position of M3 India.
About the author of this article: Dr Partha Ghosh, BNYS, MD(YS), is a general physician and a medical writer from Siliguri, Darjeeling.
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