Abstract
RAS proteins control a number of essential cellular processes as molecular switches in the human body. Presumably due to their important signalling role, RAS proteins are among the most frequently mutated oncogenes in human cancers. Hence, numerous efforts were done to develop appropriate therapies for RAS-mutant cancers in the last three decades. This review aimed to collect all of the reported small molecules that affect RAS signalling. These molecules can be divided in four main branches. First, we address approaches blocking RAS membrane association. Second, we focus on the stabilization efforts of non-productive RAS complexes. Third, we examine the approach to block RAS downstream signalling through disturbance of RAS-effector complex formation. Finally, we discuss direct inhibition; particularly the most recently reported covalent inhibitors, which are already advanced to human clinical trials.
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