Pancreatic Cancer

Pancreatic cancer can largely be divided into exocrine (95%) and endocrine (5%) tumors, whereas pancreatic ductal adenocarcinoma (PDAC) is the most common form (90%). Pancreatic cancers arise in a stepwise fashion from premalignant lesions, like pancreatic intraepithelial neoplasia (PanIN) in the case of PDAC. More than 90% of PanIN show KRAS mutations, which is the most frequent genetic alteration in pancreatic cancer. Inactivating mutations in CDKN2A, p53 and SMAD4 are detected with increasing frequency in higher grade PanIN and PDAC, indicating that these are important drivers of disease progression and SMAD4 mutations are especially associated with a high metastatic burden. A prominent feature of PDAC is a dense desmoplastic stroma, which results in poor vascularization, a hypoxic microenvironment and significantly contributes to therapy resistance, partially via impaired drug delivery. An additional important characteristic of PDAC is the immunosuppressive microenvironment, which restricts immune surveillance while it supports tumor progression via the paracrine crosstalk between tumor cells and stromal immune cells. Although immune checkpoint inhibitors showed promising results in various solid tumors, they failed to show activity in PDAC as single agents. Many combination therapies of chemotherapy together with agents that target the stroma are currently being tested; yet, so far, improving the clinical outcome of pancreatic cancer patients remains an unmet need.

TICC Faculty who are involved in Pancreatic Cancer research:

Avi Schroeder

Dov Hershkovitz

Gad Rennert

Gera Neufeld

Gil Bar Sela

Gil Ziv

Israel Vlodavsky

Ofer Nativ

Ora Israel

Ron Epelbaum

Yuval Shaked

 

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