Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.
Why is this research important: Colon cancer is the second leading cause of cancer deaths worldwide and makes up about 10% of all cancer diagnoses. Approximately 3-5% of colon cancer contain a mutation called G12c KRAS, one of a handful of cancer driving mutations in the KRAS gene. In healthy cells, KRAS functions as an ‘on/off’ gene that controls cell growth, but mutations can cause it to become stuck in the ‘on’ state, meaning that cells grow uncontrollably.
What did the researchers do: In the first part of a trial conducted by Mirati Therapeutics, 45 patients with advanced colon cancer were recruited, all having screened positive for KRAS G12C mutations. All the patients had advanced disease (their tumours continued to grow despite having had a median of three prior treatments). They were treated with the experimental drug adagrasib, which binds and blocks the activity of the G12C KRAS gene.
In a second part of the study, 28 patients with similar characteristics were recruited and treated with a combination of adagrasib and cetuximab, an existing and approved drug that blocks a growth factor called EGFR.
Key takeaway(s) from this research: With adagrasib given on its own, 10 of 45 patients, or 22%, showed partial tumour shrinkage lasting a median of 4.2 months. However, when combined with cetuximab, response rate increased to 43%, though how long this response lasts for is not yet known. This response rate is quite promising, considering that these were patients who had not responded well to previous treatments. Trials for adagrasib are still ongoing, but the drug may reach the market as early as next year.