By Jane Cook
October 15, 2021
Not all drug targets are created equal. While some drug targets readily interact with chemicals and small molecules, others stubbornly resist binding to any kind of drug.
This was the case with KRAS G12C, a previously “undruggable” mutation present in nearly 13% of non-small cell lung cancers (NSCLC). In fact, most KRAS mutations lead to extremely challenging targets, despite their ubiquity across cancer types.
In May 2021, the FDA approved Lumakras (sotorasib), a drug developed by Amgen that targets the KRAS G12C mutation in NSCLC, and two associated companion diagnostics.
Amgen researchers describe the KRAS protein as “smooth and tennis-ball shaped,” making it extremely difficult for a small molecule to bind and get a solid foothold. However, during their drug development and screening process, they identified a very small binding pocket in the G12C mutated KRAS that could bind one of their molecules in a specific orientation.
In Amgen’s phase 2 clinical trial, CodeBreaK 100, Lumakras shrank or suppressed tumor growth in 81% of patients, had a high objective response rate of 36% (over 30% is considered significant) and the response lasted a median of 10 months.
Medicine and Bioinformatics
This drug is yet another breakthrough in precision medicine and companion diagnostics at the intersection of medicine and bioinformatics. In case you didn’t know, KRAS mutations have long been targets of interest in cancer, but it took identification and modeling of a precise mutation for a successful molecule to be identified.
Further improving the drug’s specificity and efficacy is the fact that this mutation is only present in 13% of NSCLCs, demonstrating the critical need for companion diagnostics. The FDA also approved a plasma-based test by Guardant Health and a tumor tissue-based test by QIAGEN for companion diagnostics.
Bioinformatics will continue to be essential for accurate companion diagnostics for rare diseases that can be targeted uniquely by precision medicine.
Jane Cook, Journalist & Content Writer, Bridge Informatics
Jane is a Content Writer at Bridge Informatics, a professional services firm that helps biotech customers implement advanced techniques in the management and analysis of genomic data. Bridge Informatics focuses on data mining, machine learning, and various bioinformatic techniques to discover biomarkers and companion diagnostics. If you’re interested in reaching out, please email [email protected] or [email protected].