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The Glycolytic Pathway as a Target for Novel Onco-Immunology Therapies in Pancreatic Cancer
Authors:Claudia Curcio  Silvia Brugiapaglia  Sara Bulfamante  Laura Follia  Paola Cappello  Francesco Novelli
Institution:1.Department of Molecular Biotechnology and Health Sciences, University of Turin, 10126 Turin, Italy; (C.C.); (S.B.); (S.B.); (L.F.); (P.C.);2.Centro Ricerche Medicina Sperimentale, Azienda Ospedaliera Universitaria, Città della Salute e della Scienza di Torino, 10126 Turin, Italy;3.Computer Science Department, University of Turin, 10126 Turin, Italy
Abstract:Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal forms of human cancer, characterized by unrestrained progression, invasiveness and treatment resistance. To date, there are limited curative options, with surgical resection as the only effective strategy, hence the urgent need to discover novel therapies. A platform of onco-immunology targets is represented by molecules that play a role in the reprogrammed cellular metabolism as one hallmark of cancer. Due to the hypoxic tumor microenvironment (TME), PDA cells display an altered glucose metabolism—resulting in its increased uptake—and a higher glycolytic rate, which leads to lactate accumulation and them acting as fuel for cancer cells. The consequent acidification of the TME results in immunosuppression, which impairs the antitumor immunity. This review analyzes the genetic background and the emerging glycolytic enzymes that are involved in tumor progression, development and metastasis, and how this represents feasible therapeutic targets to counteract PDA. In particular, as the overexpressed or mutated glycolytic enzymes stimulate both humoral and cellular immune responses, we will discuss their possible exploitation as immunological targets in anti-PDA therapeutic strategies.
Keywords:pancreatic cancer  glycolysis  immunotherapies
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