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Sri Pothula: uncovering the secrets of pancreatic cancer

By Linda Music

Growing up in a small rural town in India, Sri Pothula could never have imagined that one day he would work on cutting-edge research which could, potentially, see a cure for pancreatic cancer.

But his path to cancer research was not straightforward. Indeed, his journey took him across multiple continents and fields of specialisation from a veterinary science degree in India to research into animal physiology and cancer cell models in the U.S. and then, finally to Australia.

Arriving in Australia with his new wife in 2011, Sri actively pursued his interest in cancer and found Professor Minoti Apte’s Pancreatic Research Group. Excited by Professor Apte’s groundbreaking work in pancreatic cancer, Sri joined the team as a sponsored PhD student. From 2012 to 2017, Sri researched pancreatic cancer specifically working on novel therapeutic approaches for pancreatic cancer targeting HGF /C-MET pathways.

Sri explains that his research followed on from the work of Professor Apte who isolated and characterised pancreatic stellate cells in 1998. These cells are the principal source of fibrosis in the stroma which surrounds the pancreatic tumour. As Sri explains, the stroma is one of the most prominent characteristics of this type of cancer.

“We had the idea that these cells, which produce the stroma, must have some mechanism or ‘language’ which allows them to interact with cancer cells to support cancer progression,” explains Sri.

Sri started looking at what this ‘language’ might be and discovered that it was the HGF/c-MET pathway.

“These pancreatic stellate cells produce HGF which act like a key fitting into the c-MET receptor, which is present on cancer cells as well as endothelial cells (the cells that line blood vessels). Once this happens, the cancer is activated, promoting cancer progression.”

This discovery led to research into ways in which they could interrupt these pathways using specific inhibitors.

They found that, when they combined their HGF/c-MET inhibitor approach with standard chemotherapy, they were able to significantly reduce tumour progression. More importantly, they were able to completely eliminate metastasis (in mouse models).

“Metastasis is the most common reason for pancreatic cancer-related deaths,” explains Sri.

However, this research was only on early pancreatic cancer models so the next step has been to investigate whether their findings could be applied in advanced pancreatic models.

“The results we are seeing are very promising. This triple therapy has worked well in advanced pancreatic cancer models and we have not seen any metastasis in this model,” says Sri. These exciting results have recently published by the group and was recently selected as CONCERT’s paper of the month (Xu et al, British Journal of cancer, March 2020).

Sri has also recently published an updated review titled “Pancreatic stellate cells: Aiding and abetting pancreatic cancer progression” earlier this year (Pothula et al, Pancreatology, January 2020).

While these findings are exciting and look promising as treatments for future cancer patients, Sri explains that the group is cautiously looking to translate their pre-clinical findings into the clinic.

“We understand that people are desperate due to the very dismal prognosis of this disease. However, we want to ensure that by doing multiple parallel testing in multiple models, our findings, when implemented in clinics, can be as foolproof as possible.”

If Sri isn’t busy enough working in pancreatic research, he is also the full-time Laboratory Manager at the Ingham Institute of Applied Medical Research.

“I look after the research infrastructure and provide scientific and technical expertise, not just in pancreatic cancer research, but in all streams of cancer research as well.”

In addition, Sri has played a key role in obtaining $400K in research infrastructure support grants which have contributed in the purchase of the latest addition to Ingham Institute’s cancer-fighting arsenal: the 3D bioprinter.

He hopes that the excellent research at Ingham Institute will continue to attract more talent and will continue to drive the institute to become a world-class medical research institute.

Sri has come a long way from his humble beginnings in rural India. He has crossed many oceans to where he is today, but his journey continues. CONCERT recognises Sri’s significant contribution to pancreatic cancer research and looks forward to seeing the continued progress of his work and that of the entire Pancreatic Research Group.