Publications by authors named "F T Sherman"
KRAS is the most frequently mutated oncogene in lung adenocarcinoma, with G12C and G12V being the most predominant forms. Recent breakthroughs in KRASG12C inhibitors have transformed the clinical management of patients with G12C mutation and advanced our understanding of its function. However, little is known about the targeted disruption of KRASG12V, partly due to a lack of specific inhibitors.
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- KRAS inhibitors like adagrasib and sotorasib can help treat lung cancers with KRAS mutations, but many patients still develop resistance over time.
- In patients with a specific type of lung cancer (adenocarcinoma) that also has STK11/LKB1 mutations, certain gene patterns can predict a poorer response to treatment.
- Research shows that these cancers can change their type to avoid being affected by the drugs, and scientists found specific markers that indicate how likely someone is to respond to KRAS treatment.
The combination of targeted therapy with immune checkpoint inhibition (ICI) is an area of intense interest. We studied the interaction of fibroblast growth factor receptor (FGFR) inhibition with ICI in urothelial carcinoma (UC) of the bladder, in which FGFR3 is altered in 50% of cases. Using an FGFR3-driven, Trp53-mutant genetically engineered murine model (UPFL), we demonstrate that UPFL tumors recapitulate the histology and molecular subtype of their FGFR3-altered human counterparts.
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- * Researchers used CRISPR/Cas9 screens to find genes whose deletion could enhance the effectiveness of a KRASG12C inhibitor (adagrasib) and a combination treatment, identifying several potentially targetable synthetic lethal genes linked to specific biological pathways.
- * These findings suggest potential new targets for combination therapies that could improve treatment outcomes for patients, especially for those whose tumors have developed resistance to existing treatments.
Introduction: In KRAS-mutant NSCLC, co-occurring alterations in LKB1 confer a negative prognosis compared with other mutations such as TP53. LKB1 is a tumor suppressor that coordinates several signaling pathways in response to energetic stress. Our recent work on pharmacologic and genetic inhibition of histone deacetylase 6 (HDAC6) revealed the impaired activity of numerous enzymes involved in glycolysis.
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