- Pharmacological inhibition of mutant KRAS has tumor-selective effects
- Novel agent MRTX1133 elicits potent disease control as a single agent
- Immune response shown to augment the therapeutic effect
Newswise — BUFFALO, N.Y. — A research study led by a multidisciplinary team of scientists at Roswell Park Comprehensive Cancer Center details evidence on the therapeutic efficacy of a compound that targets a key genetic feature of pancreatic cancer. The work, newly published in Cancer Research, a journal of the American Association for Cancer Research, illustrates potential clinical applications for the novel anticancer agent MRTX1133 and outlines its effect on both the tumor and the surrounding environment.
Most pancreatic cancers harbor mutations in the KRAS gene, which drives many of the features that make this disease so lethal. New precision agents have been developed that are selective for KRAS mutations. In this new work, the Roswell Park team explores the utility of a selective inhibitor, MRTX1133, that specifically targets KRASG12D — a mutation present in approximately half of all pancreatic cancers.
Mutation of KRAS is a major molecular driver for the development of pancreatic cancer. MRTX1133, being a selective inhibitor against mutant KRASG12D, possesses antitumor efficacy that is selective for only tumor cells that harbor this mutation — a level of precision targeting that has long been a goal for the treatment of cancer. The team used a series of laboratory cell lines and preclinical models to illustrate how the tumor itself, as well as the environment surrounding the tumor, is acted upon by MRTX1133 and how both contribute to the therapeutic response.
“Our study highlights the importance of using models that accurately capture the tumor microenvironment,” says Vishnu Kumarasamy, PhD, the lead author on the new work. “This underscores the critical role of the tumor’s surrounding environment in therapeutic response to KRAS…
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