A novel way to target KRAS mutant lung cancer
The past year has seen hype and hope over targeting KRAS mutant cancers and many challenges still remain to be addressed. We’ve seen the emergence of selective G12C inhibitors, as well as others targeting SOS1:RAS upstream and even related pathways to address cross-talk such as SHP2 and ULK1, for example. The oncology R&D ecosystem is beginning to motor again as new competitors start entering the niche.
Riding the KRAS wave
To put things into broader perspective, however, despite all the positive news in lung cancer, consider the colorectal carcinoma data was less impressive than lung because of more complex, heterogeneous disease.
Meanwhile, Lilly recently announced the discontinuation of their selective G12C inhibitor, LY3499446, due to adverse toxicity, so clearly it is not all going to be plain sailing in this landscape!
Let’s also not forget the G12C mutation is not the only viable target in this context. People with advanced lung cancer can also present with one or more of several co-occurring mutations such as the serine/threonine kinase 11 gene (STK11) and kelch like ECH associated protein 1 gene (KEAP1), for example.
Unfortunately those presenting with both STK11 and KEAP1 mutations – independent of KRAS status – often have a poorer prognosis and there remains an unmet medical need for effective new treatments.
In this fourth postcard in our summer mini-series on the potential of immunometabolism for cancer immunotherapy, we’re taking a look at a novel way to target KRAS mutant lung cancer and, in particular, those with an STK11 and KEAP1 mutation who tend to do poorly on current therapies.
To learn more about the emerging area of immunometabolism and its translational potential, subscribers can log-in or you can click to gain access to BSB Premium Content.
This content is restricted to subscribers
At the recent ASH meeting, they presented interesting preclinical data for AG-221 using IDH2 mutant AML xenografts. While in New Orleans, I had the opportunity to sit down with the Agios CEO, Dr David Schenkein, and discuss their approach, challenges and direction in some detail. He is also presenting at the JP Morgan Healthcare Conference today and giving a business update on the company’s progress.