A therapeutic method for treating oncogenic Ras-mediated tumor growth with L-NAME
In cancer, there are various gene mutations and amplifications that drive the survival and proliferation of tumors. One of the most mutated genes in cancer is the RAS gene family (HRAS, KRAS and NRAS). Approximately 30% of all cancers contain a RAS mutation. However, despite being a major player in tumorigenesis, targeting the RAS pathway has had low success in the clinic. Therefore, there is an unmet clinical need to identify novel therapeutics to treat cancers where RAS is essential for tumor growth and survival.
Counter and colleagues have identified a new therapeutic method for the treatment of oncogenic RAS-driven cancer. This is accomplished by treating patients with L-NAME, a nitric oxide synthase inhibitor. The researchers have identified that the oncogenic RAS-Akt pathway causes phosphorylation of endothelial nitric oxide synthase (eNOS) at site S1177. Through pre-clinical mouse studies and genetic manipulation of eNOS, Counter and colleagues showed that eNOS is required for tumor growth in RAS mutated cancer cells. Oral administration of L-NAME in mice bearing oncogenic RAS tumors showed decreased tumor growth.
- Targeting the downstream eNOS serves as a novel, alternative strategy for treating RAS-driven cancers
- Animal studies demonstrate decreased tumor growth
- Can treat multiple cancer types including pancreatic and non-small cell lung cancer