How AI Can Help Target a Protein That Contributes to Pancreatic Cancer

Mayo Clinic and Bengaluru-based Sravathi AI Technology have developed an AI-assisted experimental cancer treatment targeting GIPC1, a protein linked to pancreatic and other cancers.

About Pancreatic Cancer

• Pancreatic ductal adenocarcinoma (PDAC) is the most common and highly aggressive form of exocrine pancreatic cancer.
• PDAC has a five-year survival rate below 13.3%, largely due to late diagnosis, rapid progression and resistance to treatment.
• Overproduction of GIPC1 in PDAC promotes tumour growth and contributes to resistance against chemotherapy.

Why is GIPC1 a Difficult Target?

• GIPC1 does not independently cause cancer but abnormal expression or signalling allows cancer cells to grow excessively and invade other tissues.
• Its PDZ domain interacts with multiple proteins through broad and shallow surfaces, making conventional drug binding difficult.
• GIPC1 functions as a signalling hub, meaning blocking one pathway may not stop other cancer-promoting pathways.
• These characteristics have traditionally made GIPC1 an “undruggable” protein target.

How AI Helped Develop the Treatment

• Researchers used computational modelling, machine learning and predictive analytics to identify a selective small-molecule GIPC1 inhibitor.
• The experimental molecule, called GIPCi, specifically targets the PDZ domain of GIPC1.
• Researchers initially screened around 40,000 molecules, narrowed them to five candidates and synthesised and tested two.
• Generative AI helped design candidate molecules, while predictive AI assessed properties such as toxicity and absorption.
• Molecular modelling and quantum chemistry were used to predict which molecules were most likely to bind effectively to GIPC1.

Significance

• The research shows how AI can dramatically reduce the time and number of compounds required during early-stage drug discovery.
• AI-based approaches could help develop drugs against proteins that were previously considered too difficult for conventional pharmaceutical methods.
• Targeting GIPC1 could eventually provide a new therapeutic approach for pancreatic cancer and potentially other GIPC1-linked cancers.