New Combo to Boost KAS Inhibitors Activity Against Lung Cancer

Release Date: 01-Oct-2019

Recently, a team of researchers found that the by suppressing  two more tumor-related proteins along with the use of KRAS inhibitors shows positive effects in the treatment of lung cancer. The early evidence of the study shows that the combo could further increase KRAS inhibitors’ therapeutic effects in lung cancer.

The study was conducted by scientists from the Francis Crick Institute and The Institute of Cancer Research, London, and the findings were published in  Science Translational Medicine. The study involves Novartis’ mTOR blocker Afinitor (everolimus) and Astellas’ investigational anti-IGF1R linsitinib along with a KRAS-G12C inhibitor called ARS-1620, which is developed by Araxes Pharma's subsidiary Wellspring Biosciences. In the study, it is observed that shrinkage in lung tumors in mice took place and shrinkage of human cells in lab dishes were also observed.

Another study was conducted by Julian Downward and colleagues at Crick and ICR previously, who concluded that combining the inhibition of the MEK enzyme and the IGF1R receptor is able to limit KRAS-driven lung cancer cell growth. For further improvement in the result, the team screened 16,019 genes to identify pathways that could be blocked to provide additional benefits.

However, the previous study of combining the MEK inhibitor and mTOR inhibitors showed positive effects against the lung cancer, some adjustment was done in this combo. This previous combo has a variety of serious side effects, so the scientists replaced the MEK inhibitor with a direct KRAS inhibitor ARS-1620. So this combo is studied for clinical testing.

According to the senior author of the study, Tumors treated with the combination shrank and stayed small, whereas those treated with the G12C-KRAS inhibitor alone tended to shrink at first but then start growing again after a couple of weeks. The triple combinations using either ARS-1620 or Mekinist showed similar results.