Summary
KRAS mutation, previously seen as “undruggable” sees promise for new therapies through improbable targets for lung cancer.
Drugging the undruggable, improbable new targets for lung cancer therapy
KRAS mutation, considered to be hard to treat, sees promise for new therapies through improbable targets for lung cancer.
The growth of solid tumors is frequently driven by mutations in key proto-oncogenes. For non-small-cell lung cancers (NSCLC), somatic mutations in the KRAS (Kirsten RAt Sarcoma virus) gene turn it into an oncogene that renders tumors resistant to common chemotherapies like erlotinib (Tarceva) or gefitinib (Iressa).
Previously, KRAS was considered to be “undruggable” because the surface of the tiny protein had no deep pockets for drug interaction with potential small molecule inhibitors. Since many NSCLCs rely on a constitutively activated mutant KRAS, researchers have continued to explore KRAS and its downstream signaling pathways as possible targets. That research has finally begun to pay off. Complementary approaches to NSCLC lung cancer that collectively embrace immune self-defenses within the context of the larger KRAS ecosystem have now come fully into view.
Together, they flesh out a therapeutic microcosm of tumor biology that can be copied and modified to serve as a blueprint for treating many cancer types, each sustained by their own unique oncogenic drivers. In an article in Cell Reports Medicine researchers outline four ways to combat KRAS-dependent NSCLC: immune checkpoint inhibitors, KRAS neoantigen targeting, direct KRAS inhibitors and KRAS signaling inhibitors.
