7,000 cancer tissue samples, lab-grown organoids: Inside IIT-Madras’s push for precision oncology

Over the last seven years, the team has sequenced the complete exome — the protein coding regions of our genetic information, representing just over 1% of the entire genome — of several breast and oral cancer samples. Whole exome sequencing — as opposed to whole genome sequencing — is quicker, easier and cheaper to do and provides researchers with meaningful information to understand genetic diseases.

Dr Mayank Singh, medical oncologist from the All India Institute of Medical Sciences, said, “While this is not the only initiative to sequence samples of cancer patients from India, all of them are much needed. The more we sequence, the more we are likely to find targets that can be used to design therapies suited to Indian patients.”

Researchers have discovered a mutation in breast cancer samples that occur at a much higher frequency in Indian samples as compared to data available from the West. This has led them to explore whether for some Indians it is a founder mutation — a disease causing genetic mutation that occurs at a high frequency in a particular population introduced by a common ancestor. A new founder mutation can be used as a biomarker for screening for that particular type of cancer, help better ascertain the risk of that cancer in a particular population, and importantly can act as the target for newer therapies.

“Before we can say that it is a founder mutation, we need to see whether it occurs in a large number of patients and whether it is found in patients from across the country. We are in the process of doing this,” said Prof S Mahalingam, who heads the Centre of Excellence on Cancer Genomics and Molecular Therapeutics at IIT Madras.

The researchers have found a higher prevalence of triple negative breast cancer in India as compared to the rest of the world. Triple negative breast cancers lack the three common receptors targeted by breast cancer treatments, making them very difficult to treat. They are also more aggressive, tend to grow faster and have a higher recurrence. “We are now looking for biomarkers and targets in our own genomic data, which may help in early diagnosis and better treatment for this type of aggressive cancer,” said Prof Mahalingam.

A new genetic panel for pancreatic cancer, which is usually diagnosed at a very advanced stage and is difficult to treat, is also developed. “There are some unique changes that we have noted in pancreatic cancer patients from India — this data is yet to be published. But, we have already developed a genetic panel that uses the global mutations as well as the ones from India. We are waiting for a patent,” said Prof Mahalingam. The researchers are also looking for biomarkers that can be detected in blood — this will help in developing a non-invasive test for pancreatic cancer, ensuring early diagnosis.

The researchers are also looking to develop non-invasive tests for the paediatric leukaemia based on the genomic data being collected. As Dr Singh said, “It is very encouraging to hear that the researchers have found certain possible targets, the challenge now will be to design inhibitors using these targets.”