Abstract:
Cancers driven by KRAS mutations, including most pancreatic cancers and many colorectal and lung cancers, have been the most difficult to treat. KRAS cancers have been excluded from other new therapies because they do not respond. However, multiple new drugs targeting KRAS directly or indirectly have been developed and are now in clinical trials. Drugs that bind to specific KRAS mutants have been developed, some with extremely high affinity. Furthermore, drugs that prevent KRAS signaling to its downstream effectors have shown great promise in preclinical models and are now in clinical trials as single agents or in combination. This new generation of therapeutics are expected to be effective in major cancer types without significant side effects. They will provide hope for cancer patients who previously had very few options.