Samuel Kareff, Hematology/Oncology Chief Fellow at the University of Miami Sylvester Comprehensive Cancer Center, shared on LinkedIn:

“Our pan-tumor analysis on the not-so-elusive HRAS mutation in solid tumors was just released in Cancers MDPI! This labor of love was originally presented as a series of posters at the American Society of Clinical Oncology (ASCO), American Association of Cancer Research and ESMO – European Society for Medical Oncology Annual Meetings in 2022-2023.

Open-access link here.

HRASmut are much less common than KRASmut in solid tumors, but they are not negligible. In fact, there is FDA Breakthrough Therapy designation for a targeted farnesyltransferase inhibitor, Tipifarnib, in HRASmut HNSCC. But what about in other solid tumors?

We performed a retrospective analysis of 63,873 tumor samples from Caris Life Sciences and found 524 (0.8%) HRASmut. In the five most common tumor types, HRAS prevalence ranged from 3.0% in urothelial cancer to 0.44% in non-small cell lung cancer, in line with other analyses.

However, some interesting patterns emerged. There were ZERO cases of HRASmut in HER2+ BC of any HR status! HRASmut were more commonly seen in squamous Non- Small Cell Lung Cancer vs. Lung Adenocarcinoma. (Our paper details additional patterns in co-alterations and biomarkers.) Importantly, patients with HRASmut HNSCC demonstrated worse OS compared to patients without HRASmut! (N.B. tipifarnib received FDA breakthrough in 2021).

What might we do with this information?

• Continue researching about tipifarnib (mono- or in combination) in HRASmut tumors (Current list here.
• Include HRASmut when evaluating pan-RAS inhibitors.
• Closely monitor patients with this subset of disease.

Huge thanks to Gilberto Lopes, Asaad Trabolsi, Harris Krause, Timmy Samec, Andrew Elliott, Estelamari Rodriguez, Coral Olazagasti,  Dionysios C. Watson, Matias Bustos, Dave Hoon, Stephanie Graff, Emmanuel Antonarkis, Sanjay Goel and George Sledge. Also the institutional sponsors Sylvester Comprehensive Cancer Center and Caris Life Sciences.”

Source: Samuel Kareff/LinkedIn