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KRAS Mutant Pancreatic Cancer: No Lone Path to an Effective Treatment

Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Author to whom correspondence should be addressed.
Academic Editor: Jonas Cicenas
Cancers 2016, 8(4), 45;
Received: 23 February 2016 / Revised: 8 April 2016 / Accepted: 11 April 2016 / Published: 18 April 2016
(This article belongs to the Special Issue Small GTPases in Cancer)
Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest cancers with a dismal 7% 5-year survival rate and is projected to become the second leading cause of cancer-related deaths by 2020. KRAS is mutated in 95% of PDACs and is a well-validated driver of PDAC growth and maintenance. However, despite comprehensive efforts, an effective anti-RAS drug has yet to reach the clinic. Different paths to inhibiting RAS signaling are currently under investigation in the hope of finding a successful treatment. Recently, direct RAS binding molecules have been discovered, challenging the perception that RAS is an “undruggable” protein. Other strategies currently being pursued take an indirect approach, targeting proteins that facilitate RAS membrane association or downstream effector signaling. Unbiased genetic screens have identified synthetic lethal interactors of mutant RAS. Most recently, metabolic targets in pathways related to glycolytic signaling, glutamine utilization, autophagy, and macropinocytosis are also being explored. Harnessing the patient’s immune system to fight their cancer is an additional exciting route that is being considered. The “best” path to inhibiting KRAS has yet to be determined, with each having promise as well as potential pitfalls. We will summarize the state-of-the-art for each direction, focusing on efforts directed toward the development of therapeutics for pancreatic cancer patients with mutated KRAS. View Full-Text
Keywords: RAS; pancreatic; cancer; therapeutics RAS; pancreatic; cancer; therapeutics
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MDPI and ACS Style

Zeitouni, D.; Pylayeva-Gupta, Y.; Der, C.J.; Bryant, K.L. KRAS Mutant Pancreatic Cancer: No Lone Path to an Effective Treatment. Cancers 2016, 8, 45.

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