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Why do Targeted Cancer Therapies become Resistant over time?

Nov 20, 2019

Highlights

A recent study published in the journal science has shown that colorectal cancer cells when treated with targeted cancer therapy like Cetuximab or Dabrafenib develops resistance by altering specific genes and pathways that enable the cancer cells to mutate further and become more aggressive and resistant.



Targeted Cancer Therapy

Every year, millions of people around the globe are encouraged and sometimes required to take their daily vaccinations against potential disease outbreaks. However, just getting a shot once may not completely eliminate the risk of a certain bacteria or virus because pathogens have the ability to evolve and get even stronger, which is why scientists and medical professionals have to constantly monitor and design new and updated vaccine strains. Similarly, there is a notion that targeted cancer therapy, a form of chemotherapy in which drugs directly attack the specific genes or environment of the tumor, is better than regular chemotherapy because it is more specific in its attack. Chemotherapy in this context include both chemical and biological antibody drugs. Cancer cells, like bacteria and viruses, also have the ability to continuously modify and mutate their internal systems to dodge the attacks and become resistant to targeted chemotherapies.

Targeted Therapy Resistance Mechanisms

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Essentially, when any type of chemotherapy, including targeted chemotherapy treatment is initiated in a patient, it is initially effective and wipes out most cancer cells, except for a few that become resistant due to ongoing mutations. The question is whether these resistant cells are able to mutate at a faster rate than the rate of killing of the responsive cancer cells, thus increasing in percentage and making the tumor more aggressive and resistant to the targeted therapy. And to test this, medical researchers from Italy in collaboration with Harvard School of Public Health, did a study involving colorectal cancer cells treated with the targeted therapy Cetuximab, an antibody drug specifically targeted to EGFR (epidermal growth factor) receptors, and Dabrafenib, a small molecule drug targeted to the BRAF oncogene. In this study, they found that through the downregulation of genes that are involved in repairing DNA damage and mutations and upregulation of genes that will copy the DNA despite being damaged, “tumor cells evade therapeutic pressures by enhancing mutability” (Russo M et al, Science. 2019).

The implications of this study are pretty significant in terms of how one views the effects of even the latest forms of cancer treatment. The reason why targeted chemo therapies have been gaining in popularity is because some of the drugs have become so advanced that they are able to only have toxic effects on the mutated cancer cells and not harm a patient’s normal cells, thus reducing the severe side-effects of routine chemotherapy. In terms of what was possible 20-30 years ago, a treatment like this is revolutionary. However, despite the personalized and targeted therapy approach that has helped tackle some highly resistant cancers, the development of further and ongoing resistance has become a major hurdle for targeted therapies. What is needed is a personalized approach that instead of using a targeted therapy individually, strategically combines therapies based on the unique genomic and molecular characteristics of each patients’ cancer as a multi-pronged attack addressing all the possible resistance mechanisms that the cancer cell may employ to escape getting wiped out.


Cancer patients often have to deal with different chemotherapy side effects which affect their quality of life and look out for alternative therapies for cancer. Taking the right nutrition and supplements based on scientific considerations (avoiding guesswork and random selection) is the best natural remedy for cancer and treatment related side-effects.


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