Understanding the link between genes and lung cancer

Updated : November 21, 2020 20:51:43 IST

Lung cancer can be broadly classified into non-small cell lung cancer and small cell lung cancer

Oncologists have adopted a practice of understanding gene mutations for prescribing the precise course of treatment.

Based on the gene/biomarker mutations there are various agents available for targeted treatment.

The projected incidence of patients with cancer in India among males is 679,421 (94.1 per 100,000) and among females 712,758 (103.6 per 100,000) for the year 2020. Lung cancer can be broadly classified into non-small cell lung cancer (NSCLC, accounting for 80-85 percent of all lung cancer cases) and small cell lung cancer (~15 percent of all lung cancer cases).

The cause of cancer cannot be pinpointed as it is multifactorial in origin. Interaction between a person’s genetic factors and the different types of external carcinogenic agents such as ultraviolet and ionizing radiation, chemicals such as tobacco smoke components, asbestos, and infections from certain pathogens such as human papillomavirus, is what results in the abnormality in cells. Other factors include aging and physical inactivity. These abnormalities in cells stem to changes in the DNA sequence of the cell, called a mutation, that leads to carcinogenesis.

As the paradigm of cancer treatment has rapidly shifted, today, biomarker-based treatment has become the standard of care. Oncologists have adopted a practice of understanding gene mutations for prescribing the precise course of treatment. There are various biomarkers that can be studied in the case of lung cancer including EGFR, KRAS, ALK, ROS1, NTRK and other genes for targeted therapy as well as PDL1 marker and tumor mutation burden for immunotherapy decisions. Based on the gene/biomarker mutations there are various agents available for targeted treatment. E.g EGFR inhibitors have shown a better effects on patients with EGFR mutations, NTRK inhibitors for patients with NTRK gene fusions and so on.

There is in fact an interesting story behind initial clinical trial results of EGFR inhibitors. The clinical trials were undertaken in the west and the east independently. There was no marker-based selection criterion for the candidates to undertake the trials for this drug. The results in both the trials were nowhere like each other. In the west, the percentage of candidates on whom the drug showed comparatively better results was below average. And hence post spending billions of dollars on the drug, it was on the verge of being rejected by the FDA. However, in the east, surprisingly, it showed a completely opposite result and there were a high percentage of candidates on whom there was a remarkably better effect of the drug. While this brought back the hopes, the reason behind this was still a mystery for the researchers.

Later, while analyzing the data in detail, the reason behind this mismatch was discovered. Asians have a comparatively higher population with EGFR mutations compared to the Caucasian population. Also, because the selection of candidates for the trials was not done based on the presence/absence of mutation, the visible difference was stark. This is one of the many serendipities of drug development and approval process in the pharmaceuticals and healthcare world.

With science behind genomics evolving rapidly, the treatment landscape has changed massively in the last 2 decades. This disease that was treated only with radiation and chemotherapy is now treated with multiple targeted therapeutic drugs, thanks to biomarker-based treatment options. However, there is a lot yet to be done and we are hopeful of genomics and molecular testing making a huge impact in reducing the mortality rate of lung cancer.

(The author is Dr Arun Kumar, Scientist at MedGenome Labs)

Disclaimer: Views expressed are personal

Published : November 21, 2020 08:51 PM IST

Understanding the link between genes and lung cancer

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