Personalized therapy for pancreatic cancer: Do we need better targets, arrows, or both?

Abstract

Pancreatic cancer is predicted by the Pancreatic Cancer Action Network to soon become the 2nd leading cause of cancer related deaths in this country. This cannot be attributed to a lack of resources focused on interrogating the genomic landscape of pancreatic cancer genomes. Additionally, a large number of researchers and federal dollars have been directed towards inhibiting the most frequent genetic lesion in pancreatic cancer, Kras. Even with these advances, cytotoxic chemotherapy is currently the best option for patients with metastatic disease. Besides developing better early detection strategies, translating our knowledge of the molecular aspects of pancreatic cancer to the clinic via a targeted, personalized medicine approach may be the best way to dramatically improve patient outcomes. Herein, we briefly describe the scope of the problem in targeting pancreatic cancer on both the cellular and molecular levels. We also outline some promising, ongoing efforts to develop better therapeutic interventions for this deadly disease. For instance, we discuss novel strategies to target molecules and pathways that go beyond targeting genetic mutations and the level of transcriptional gene regulation. Finally, we summarize a clinical trial that is designed to answer the question whether with the available arsenal of drugs and molecular targets, can we now "personalize" therapy for pancreatic cancer patients?