The recent enthusiasm over new discoveries in cancer immunotherapy has made it painfully evident how difficult progress in the therapy of pancreatic cancer has been and how very difficult it remains. If you are lucky (25% of those diagnosed), you are able to undergo curative resection to then recover and sustain 6 months of adjuvant chemotherapy followed by intensive surveillance to detect a likely recurrence (median survival of 28 months in the most recent ESPAC-4 study). If unlucky, and the disease is metastatic, median survivals have yet to exceed 12 months. To date, all preclinical insights have met an unforgiving reality test when they arrived in the clinic. Indeed, several meta-analyses have shown the difficulty of improving over gemcitabine monotherapy; almost 14,000 patients across 47 trials invested in developing current best therapies (1–5). These numbers from investigators around the world are a testament to the efforts expended. We can argue that the majority of these studies have tried to make incremental changes, usually by adding an existing agent with supporting data that all too often was at best modest. But we can also argue that at present, our knowledge about pancreatic cancer is rapidly expanding, and novel insights may yet bring a change. In this spirit, this CCR Focus aims to highlight new discoveries in pancreatic cancer genetics, including the foundational mutational signatures at the DNA level, bring new understanding to the tumor microenvironment and how normal components of pancreatic inflammatory response have been appropriated to maintain the malignant phenotype, investigate the failure of immunotherapy in pancreatic cancer to date and propose strategies to bring the immune system to bear in therapy, and outline novel approaches ongoing in the clinic. Guest Editors Dan Von Hoff and John Chabot and I have assembled a group of experts in the field to frame these discoveries and insights. As with every issue of CCR Focus, the goal is to inform the interested nonexpert and to encourage and stimulate the experts working in the field, and thus contribute to the search for new therapies for our patients.
Susan E. Bates
Deputy Editor, CCR Focus
Columbia University Medical Center
See all articles in this CCR Focus section, “Pancreatic Cancer: Challenge and Inspiration.”
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