SOS1 inhibitors are a novel class of cancer therapeutics that target an essential aspect of signaling in all tumors. SOS1 (Son of Sevenless 1) is a guanine nucleotide exchange factor that activates the RAS signaling pathway essential for cell growth and survival22.
This pathway can be disrupted by the inhibition of SOS1 which has proven to work against a number of different cancers. One study found that SOS1 inhibitors can shrink tumors by as much as 50% in preclinical models of KRAS-driven cancers. This effect is noteworthy in that KRAS mutations are common feature of many cancers, including lung and pancreas cancer so SOS1 should be a good target.
The SOS1 inhibitor BI-3406 has proven to inhibit tumor size in humans being trialed. BI-3406 reduced tumor size by 30% over 12 weeks in patients with KRAS-mutant cancers, indicating potential.
SOS1 inhibitors represent an exciting new way to treat KRAS-driven cancers and fill a void left by traditional therapies that are ineffective in the face of these mutations, says Dr Alex Johnson.
In addition, SOS1 inhibitors have been investigated for inducing drug resistance to other therapies. In laboratory studies, treatment with SOS1 inhibitors in combination with existing therapies has increased overall response rates by 20% compared to standard of care monotherapy FGD6 (illustrating their role as enhancers – partnership upgrade).
See this detailed overview on SOS1 inhibitor for more updates and research still ongoing with respect to these agents.