The pre-clinical study published by the prestigious international journal Gut demonstrates how PI3K-C2γ plays a key role in the development of one of the most aggressive cancers.

A new preclinical study, carried out in the “Guido Tarone” Center for Molecular Biotechnology of the University of Turin, made it possible to discover a new targeted therapy for a subgroup of patients affected by pancreatic ductal adenocarcinoma. The research group of the Department of Molecular Biotechnology and Health Sciences, led by Prof. Miriam Martini and Prof. Emilio Hirsch, has shown that the PI3K-C2γ protein plays a key role in the development of pancreatic cancer. This study has made it possible to shed light on the mechanisms of development of this tumor and might, in the future, maximize the effecacy of the current therapeutic options for one of the most aggressive tumors.

In the world, the number of new cases of pancreatic cancer is increasing of about 1% and the 5-year survival rate is less than 10%. Pancreatic cancer is expected to become the second leading cause of cancer death by 2030. The severity and lack of effective treatments need efforts to search for new therapies and markers that help in choosing the most effective drug.
To grow, cancer cells need nutrients and energy sources. The aggressiveness of pancreatic cancer is due to the ability to adapt to adverse conditions, such as the paucity of nutrients and energy sources, which are exploited by cells to survive. Recently, drugs have been developed that prevent the use of these nutrients, such as glutamine.

PI3K-C2γ controls the intracellular signaling pathway of mTOR, which regulates cell metabolism and growth, and affects the use of glutamine to promote tumor progression. In pancreatic cancer, the PI3K-C2 protein is lost in about 30% of patients, who develop a more aggressive form of the disease

Dr. Maria Chiara De Santis, first author of the study published in the prestigious international journal Gut, has shown that the loss of PI3K-C2γ accelerates tumor development, but makes it more sensitive to drugs that affect mTOR and to the use of glutamine.

The study led by the UniTo scientists was the result of intense collaborative work with groups in the Italian and international territory and the Italian Pancreatic Cancer Community (I-PCC), including those of Prof. Francesco Novelli, Prof. Paola Cappello and Prof. Paolo Ettore Porporato (University of Turin), Prof. Andrea Morandi (University of Florence), Prof. Vincenzo Corbo and Prof. Aldo Scarpa (University of Verona), Prof. Gianluca Sala and Prof. Rossano Lattanzio (University of Chieti) and Prof. Elisa Giovannetti (University of Amsterdam and Pisana Foundation for Science).

Here the link to the paper: Lysosomal lipid switch sensitises to nutrient deprivation and mTOR targeting in pancreatic cancer, Gut, https://gut.bmj.com/content/72/2/360