Patients with pancreatic cancer have not benefited from recent improvements in overall survival brought about by precision medicine in other malignancies. This failure is not due to a dearth of precision-medicine research in pancreatic ductal adenocarcinoma (PDAC), the main type of pancreatic cancer. In fact, the stalled progress in precision therapies for this type of cancer is due to the absence of agents that are able to target the common genetic alterations in PDAC. Several studies have attempted to phenotypically stratify PDAC at the transcriptional level. However, the value of such classifications will only be revealed through prospective studies and, crucially, only after development of new treatment options for this disease. Therefore, it is essential to learn from breakthrough discoveries in other cancer types that could benefit subpopulations of patients with PDAC and convert them from ordinary to exceptional responders. Identifying these exceptional patients will help to bring PDAC in line with other cancer types in terms of availability of precision therapies. Thus, the true challenge to precision medicine for PDAC might be the poor consensus on which genetic and phenotypic alterations across the spectrum of this disease are actionable; not the absence of actionable variables themselves. To reach consensus, knowledge and tools must be developed and disseminated for individuals who provide pancreatic cancer care, to enable the real-time identification of exceptional patients, more precise subgroup classifications, and effective disease management strategies; all informed by immediate feedback from clinical outcome data.
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