4 minute read
Cancer research more promising than ever
Dr Vignesh Narasimhan is a Colorectal Fellow who undertook a PhD at the Peter MacCallum Cancer Centre in Melbourne. He was a recipient of the prestigious Tour De Cure Cancer Research Scholarship, a scholarship that is awarded annually. Dr Narasimhan was awarded the scholarship in 2019. “Research was something I was keen on doing during my training as well. However, when you're training, a PhD is not something you do part-time—you need to dedicate a full-time schedule to it”, Dr Narasimhan said. He spent three years, from 2017 to 2019, completing his PhD at the Peter MacCallum Cancer Centre in Melbourne. His research focused on personalised therapy and exploring the immune landscape for patients with colorectal peritoneal metastases. “You're doing something completely different every three or four months—it’s always very challenging. But once you find your feet it is very rewarding,” he said. Dr Narasimhan’s attraction to cancer research came from an interest in the available treatments being offered to patients with metastatic colorectal cancer. Over a quarter of patients with bowel cancer present with stage 4 disease, where the cancer has spread to other sites. The cancer usually spreads to one of three sites—the liver, the lung, and the peritoneum. The peritoneum is the lining over the organs and what he says is an often ignored area. “This is one area that has been left behind for many, many years. A small proportion of patients, if they have very limited disease, are eligible for aggressive surgery that clears all the disease from the peritoneal cavity,” he said. The treatment for most patients with non-operable peritoneal disease, has been limited to systemic chemotherapy, which doesn't work very well in peritoneal disease. “The reasons for poor response to standard chemotherapy in peritoneal disease are believed to be multifactorial; such as poor blood supply to the peritoneal lining, inability of the chemotherapy to reach there, or chemoresistance due to altered tumour biology,” Dr Narasimhan said. A large part of Dr Narasimhan’s research was to try and develop a personalised medicine platform for patients with peritoneal disease and who failed standard treatment. He set up an international collaboration between Peter MacCallum Cancer Centre in Melbourne,
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Queen Elizabeth Hospital and SAHMRI in Adelaide as well as a team in Seattle and New York.
“What we did was sample the peritoneal tumours and grow them in the lab as novel mini tumours, called organoids. We subsequently sequenced them to evaluate their mutation profile and then drug tested them across more than 100 drugs, including chemotherapies, targeted therapies and clinical trial drugs—many of which were not used normally in bowel cancer treatment,” he said. What Dr Narasimhan found was many of the tumours were very resistant to standard drugs, in keeping with what we see in clinical practice. More importantly, some patients had a good response to drugs that were not normally used in bowel cancer treatment. “One patient in their 40s who had failed all standard lines of treatment and was not eligible for any clinical trials was found to have good response to a drug often used in pancreatic cancer. The early data was very promising.” While the prospect of a clinical trial requires more funding and getting pharmaceutical companies on board, Dr Narasimhan is optimistic that it can be established soon.
Another crucial aspect of Dr Narasimhan’s research was on the immune landscape. “We used various lab-based techniques to evaluate the immune makeup of colorectal peritoneal metastases, and to see if altering the immune microenvironment can provide a therapeutic option. This was something that had never been done before,” he said. The results, which are promising, need to be expanded and validated with a larger cohort. In his free time, Dr Narasimhan enjoys spending time with his wife and their two-year old son. He is also an avid tennis player, but says his skills are “average, not great.”. RACS Research Scholarships and Grants round opens for applications in March 2022. For more information please go to www.surgeons.org/scholarships or contact the Scholarship and Grant Coordinator at: scholarships@surgeons.org For more information on setting up a scholarship, Fellowship or grant of your own, please contact the Foundation for Surgery at foundation@surgeons.org or +61 3 9249 1110.
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