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Antitumor effect of a small-molecule inhibitor of KRASG12D in xenograft models of mucinous appendicular neoplasms

Pseudomyxoma peritonei (PMP) is a rare disease characterized by a massive accumulation of mucus in the peritoneal cavity. The only effective treatment is aggressive surgery, aimed at removing all visible tumors. However, a high percentage of patients relapse, with subsequent progression and death. Recently, there has been an increase in therapies that target mutated oncogenic proteins. In this sense, KRAS has been reported to be highly mutated in PMP, with KRASG12D being the most common subtype. Here, we tested the efficacy of a small-molecule KRASG12D inhibitor, MRTX1133, in a high-grade PMP xenograft mouse model carrying a KRASG12D mutation. The results obtained in this work showed a profound inhibition of tumor growth, which was associated with a reduction in cell proliferation, an increase in apoptosis, and a reduction in the MAPK and PI3K/AKT/mTOR signaling pathways. In conclusion, these results demonstrate the high potency and efficacy of MRTX1133 in KRASG12D-PMP tumors and provide a rationale for clinical trials.

 

Comments:

That sounds like promising research! Targeting specific mutations like KRASG12D in Pseudomyxoma Peritonei (PMP) using inhibitors like MRTX1133 seems to have shown significant effectiveness in inhibiting tumor growth. The observed reduction in cell proliferation, increase in apoptosis, and the impact on signaling pathways like MAPK and PI3K/AKT/mTOR signify potential avenues for treating this condition.

Moving from preclinical models to clinical trials based on these findings could potentially offer new treatment options for patients with PMP. Clinical trials will help further assess the safety and efficacy of MRTX1133 in human subjects, and if successful, it could pave the way for a novel therapeutic approach for PMP.

It's exciting to see advancements in targeted therapies that address specific genetic mutations associated with certain cancers, offering hope for more effective treatments.

Related Products

Cat.No. Product Name Information
E1051 MRTX1133

MRTX1133 is a highly selective inhibitor of mutant KRAS G12D and can reversibly binds to the activated and inactivated KRAS G12D mutants and inhibit their activity. The specificity of MRTX1133 to KRAS G12D is more than 1000 times that of wild-type KRAS.

Related Targets

Ras