Abstract
Pancreatic cancer is a highly lethal cancer type. The genomic landscape of the pancreatic cancer genome features four frequently mutated genes (KRAS, CDKN2A/p16, TP53 and SMAD4/DPC4) and dozens of candidate driver genes altered at low frequency, including potential clinical targets. Molecular profiling of tumor specimens has revealed potential targets for personalized anticancer therapy and seen a shift toward an emerging molecular taxonomy of cancer. We are increasingly becoming aware of the problem of intra-tumor heterogeneity. Intra-tumor heterogeneity poses a challenge to personalized cancer medicine because a single needle biopsy or surgical excision is unlikely to accurately capture the complete genomic landscape of a patient's cancer. Furthermore, studies for molecular screening often exclude some patients because of inability to obtain a biopsy, insufficient or no tumor content in the available specimen, or deteriorating performance status. The presence of tumor-derived DNA in circulating cell-free DNA provides a less-invasive approach to diagnose cancers, monitor chemotherapy-resistant mutations and overcome the problem of tumor heterogeneity. Genomic characterization of cell-free circulating tumor DNA may offer an opportunity to assess clonal dynamics throughout the course of a patient's illness and identify drivers of therapeutic resistance. As technology advances, it may be possible to perform targeted molecular analysis using "liquid clinical sequencing" using circulating cell-free DNA. This approach could solve many of the problems that we have encountered in obtaining tumor tissue. Significant efforts are under way to explore these approaches for "Precision Medicine".
