Progress and Challenges with Inhibition of K-Ras GTPase in Cancer

Dear Colleagues,

For decades, activated by mutations K-Ras GTPase has been an important cancer drug target, but still, there are no approved inhibitors for clinical use. The reasons are multiple, including alternative ways of post-translational processing, the lack of deep pockets for high affinity inhibitor binding, and compensatory pathways for downstream signalling. Now, several K-Ras inhibitors are undergoing clinical trials and more inhibitors are under consideration for testing in cancer patients. These developments suggest that many hurdles with inhibiting K-Ras in cancer have been finally overcome. Significant progress with the development of novel inhibitors of K-Ras urges the research community to address different questions, such as “Which oncogenic mutants of K-Ras can be targeted by the available inhibitors?”, “What types of K-Ras-driven cancer can be most effectively treated with these compounds?, or “Are there any potential mechanisms of resistance to K-Ras inhibition and how this resistance can be avoided?”. Answers to these questions will likely shape future research to optimize the current K-Ras inhibitors and to develop innovative strategies for enhanced blocking of K-Ras signalling in cancer. This Special Issue will focus on analysis of the available approaches to K-Ras inhibition, identification of the patient populations that will benefit the most from the current anti-K-Ras compounds, understanding potential resistance to K-Ras inhibition, and outlining plans to address emerging limitations of K-Ras inhibitors.

Prof. Vadim Gaponenko
Prof. Gary A. Piazza
Guest Editors

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