ras gene family

What Are the Therapeutic Approaches Targeting Ras Mutations?

Given the pivotal role of Ras mutations in cancer, there has been significant interest in developing therapies that target Ras signaling. Some of the approaches include:
1. Direct Inhibitors: Efforts to develop small molecules that directly inhibit mutant Ras proteins have faced challenges due to the high affinity of Ras for GTP/GDP and the lack of suitable binding pockets. However, recent advances have led to the development of KRAS G12C inhibitors that show promise in clinical trials.
2. Downstream Pathway Inhibitors: Since Ras activates several downstream pathways, targeting these pathways provides an alternative approach. For example, inhibitors of the MAPK/ERK pathway and the PI3K/AKT/mTOR pathway are being explored.
3. Synthetic Lethality: This approach involves targeting secondary vulnerabilities in cancer cells with Ras mutations. For instance, combining Ras pathway inhibitors with other drugs that target compensatory survival pathways can lead to synergistic effects.

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