Ras, the Abstruse Elephant in the Room (#200)
The association of oncogenic K-Ras with pancreatic cancer (PC) has been known for at least 12 years. K-Ras was shown to be mutated to its oncogenic form in the vast majority of pancreatic cancer in humans that long ago. However, early attempts to use this molecule as a specific biomarker of the disease were unsuccessful. Likewise, early attempts to inhibit oncogenic K-Ras activity as a cancer therapy failed. This left a situation in which this obviously key oncogene in PC became the “elephant in the room”. Everyone knew it was there, but no one was sure what to do about it. Fortunately, new insights are changing this picture and at the same time the new data suggests that many of the assumptions made about this molecule and its role in the disease may not have been correct. Several factors have contributed to these advances: in particular sophisticated genetically engineered mouse models have allowed studying in detail all the phases of carcinogenesis within an intact organism. We will discuss the advances as well as the limitations of the current-state of the art knowledge on K-Ras and try to make this elephant a bit more comprehensible. Finally, we will discuss open questions and future directions the field is likely to move towards.