One of the primary obstacles in cancer therapy is the emergence of drug resistance among cancer cells, which frequently results in the failure of treatment. The term "resistance" in the context of cancer treatment generally pertains to the capacity of cancer cells to avoid or endure the effects of therapeutic interventions.

What causes cancer treatments to become ineffective?  

In a discussion with, Dr. Anjali Kulkarni, Vice President of RWE Strategy and Analytics and an Oncologist at 4baseCare, clarified, “Drug resistance indicates that cancer cells do not react to the treatment as anticipated. There may be a partial response, or in certain instances, the disease may recur despite the implementation of the most effective treatment protocols. Drug resistance can sometimes develop rapidly, within weeks of initiating treatment, while in other situations, it may take months or even years to manifest.”

Dr. Sandeep Nayak, the Director of the Department of Surgical Oncology at Fortis Hospital on Bannerghatta Road in Bengaluru, shared his insights on the implications of the body resisting cancer treatment. He stated, “Cancer therapies, including chemotherapy, are intended to target cells that divide rapidly, which encompasses cancer cells. However, normal cells in areas such as the bone marrow, digestive system, and hair follicles may also be impacted, resulting in various side effects.”

He further explained, “In the context of cancer treatment, the term 'resistance' typically pertains to the cancer itself rather than the body. Resistance arises when cancer cells adapt or develop strategies to survive despite ongoing treatment. This adaptation can lead to a decrease in the effectiveness of the treatment or render it entirely ineffective over time. For instance, cancer cells may undergo mutations or activate survival pathways that enable them to avoid being destroyed by the medication.”

What factors contribute to treatment or drug resistance in cancer patients? Dr. Anjali Kulkarni noted that numerous factors can influence drug resistance, making it challenging to pinpoint a specific cause. She stated, “The interplay between cancer cells, their surrounding environment, the immune system, and metabolic changes significantly contributes to drug resistance. Within a tumour, cancer cells may exhibit diverse molecular markers, some of which can lead to resistance. Additionally, factors such as tumour burden and specific genetic alterations can modify the response to treatment.”

According to Dr. Sandeep Nayak, resistance to cancer treatment can develop through various mechanisms, including:

• Genetic Mutations in Cancer Cells: Cancer cells may undergo mutations that render them less vulnerable to therapeutic agents. For instance, alterations in the EGFR gene can result in resistance to targeted therapies such as tyrosine kinase inhibitors.

• Drug Efflux Mechanisms: Cancer cells might acquire the capability to expel the drug via proteins like P-glycoprotein, thereby diminishing the drug's efficacy.

• Tumour Microenvironment: The surrounding environment of the tumour, which includes immune cells, blood vessels, and the extracellular matrix, can shield cancer cells from therapeutic interventions. For example, hypoxic conditions (low oxygen levels) within the tumor microenvironment can impair the effectiveness of radiation therapy.

• Cancer Stem Cells: Certain cancers harbour a minor subset of cancer stem cells that possess intrinsic resistance to treatment and have the potential to regenerate the tumour following therapy.

• Epigenetic Changes: Modifications in gene expression that do not involve changes to the DNA sequence can also play a role in resistance. For example, cancer cells may silence genes that would otherwise render them sensitive to treatment.

• Immune Evasion: In the context of immunotherapy, cancer cells may avoid detection by the immune system by downregulating molecules such as PD-L1 or by mutating the antigens targeted by immune cells.

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