Friday, November 17, 2023

Journal Club: With Comprehensive Sequencing, Many Cancers Still Lack "Actionable Mutations"

Debate over how "actionable mutations" are defined, and how common they are, has gone on for a decade.  A major new article by Suehnholz et al. updates us with data from 47,000 annotated solid cancers tested with the MSK IMPACT assay.   

From 2017 to 2022, just five years, the rate of actionable mutations (defined year to year by the database OncoKB) has risen from 9% to 32%.   (The other 68% of solid tumors assessed by MSK IMPACT included those with "no" actionability as well as "limited" actionability.  Such tumors most often had a TP53 mutation.)    

The article suggests that the development of new therapies  against tumors driven by common tumor suppressor genes or transcription factors, will be crucial to further progress, while acknowledging this has been challenging to date.  (For a 2023 review on drugging p53 see Hassin & Oren, open access, Nature Drug Discovery, here.)

Open access:

Quantifying the Expanding Landscape of Clinical Actionability for Patients with Cancer, in Cancer Discovery (2023).   Suehnholz et al. (senior author, Chakravarty).

Coverage and interviews at Precision Oncology News here.