NEW YORK – The Institute of Cancer Research (ICR) in London said on Wednesday it is working with the Bellvitge Biomedical Research Institute (IDIBELL) and Vivan Therapeutics to discover and develop KRAS-targeted oncology drugs using artificial intelligence.
The collaborators will focus on uncovering KRAS-targeted drugs that can counteract resistance to currently available KRAS inhibitors. While patients initially respond well to KRAS inhibitors, they eventually become resistant to treatment within a few months.
In the US, there are presently two KRAS inhibitors available for advanced non-small cell lung cancer patients with KRAS mutations: Amgen's Lumakras (sotorasib) and Mirati Therapeutics' Krazati (adagrasib). The UK's Medicines and Healthcare Products Regulatory Agency and the European Commission have both granted conditional approval to Amgen's drug, called Lumykras outside the US.
The researchers involved in the present collaboration aim to design small molecule drugs that can simultaneously target KRAS and other cancer-driving proteins to overcome resistance by leveraging the expertise at three organizations. Paul Workman at ICR is a leader in the discovery of small-molecule cancer drugs, and Albert Antolin at IDIBELL in Barcelona is using big data and AI approaches to facilitate drug discovery. Researchers will use computational methods to identify promising compounds and test them in cancer cell lines and in fruit fly models with KRAS mutations developed by Vivan Therapeutics.
The London-based biotech offers a service, called the Personal Discovery Process, in which it performs exome sequencing on a patient's tumor, engineers the mutations detected in that patient's tumor network into fruit fly avatars, and screens drugs on these avatars to identify the treatments most likely to benefit patients. Vivan Therapeutics also has a collection of fruit fly models with defects in KRAS, both alone and in concert with mutations in other genes, that cause tumor cells to proliferate.
If the compounds discovered using these tools can effectively slow cancer growth in the fruit fly models, then researchers will move the drug candidates into the next stage of development.
"Our goal is to find safe and effective new drugs that are less likely to evoke resistance than current drugs by targeting multiple weaknesses in cancer at once — and that ultimately benefit cancer patients by giving them new treatment options that last longer than those that are currently available," Workman, group leader of the signal transduction and molecular pharmacology team at the ICR, said in a statement.