Antitumor effect of a small-molecule inhibitor of KRAS G12D in xenograft models of mucinous appendicular neoplasms.

Autor: Vázquez-Borrego MC; Maimonides Biomedical Research Institute of Córdoba, Córdoba, Spain.; Department of Biochemistry and Molecular Biology, University of Córdoba, Córdoba, Spain., Granados-Rodríguez M; Maimonides Biomedical Research Institute of Córdoba, Córdoba, Spain.; Department of Biochemistry and Molecular Biology, University of Córdoba, Córdoba, Spain., Bura FI; Maimonides Biomedical Research Institute of Córdoba, Córdoba, Spain.; Department of Biochemistry and Molecular Biology, University of Córdoba, Córdoba, Spain., Martínez-López A; Maimonides Biomedical Research Institute of Córdoba, Córdoba, Spain.; Pathology Unit, Reina Sofía University Hospital, Córdoba, Spain., Rufián-Andújar B; Maimonides Biomedical Research Institute of Córdoba, Córdoba, Spain.; Surgical Oncology Unit, Surgery Department, Reina Sofía University Hospital, Córdoba, Spain., Valenzuela-Molina F; Maimonides Biomedical Research Institute of Córdoba, Córdoba, Spain.; Surgical Oncology Unit, Surgery Department, Reina Sofía University Hospital, Córdoba, Spain., Rodríguez-Ortiz L; Maimonides Biomedical Research Institute of Córdoba, Córdoba, Spain.; Surgical Oncology Unit, Surgery Department, Reina Sofía University Hospital, Córdoba, Spain., Haro-Yuste S; Pathology Unit, Reina Sofía University Hospital, Córdoba, Spain., Moreno-Serrano A; Maimonides Biomedical Research Institute of Córdoba, Córdoba, Spain., Ortega-Salas R; Maimonides Biomedical Research Institute of Córdoba, Córdoba, Spain.; Pathology Unit, Reina Sofía University Hospital, Córdoba, Spain., Pineda-Reyes R; Maimonides Biomedical Research Institute of Córdoba, Córdoba, Spain.; Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Córdoba, Spain., Michán C; Maimonides Biomedical Research Institute of Córdoba, Córdoba, Spain.; Department of Biochemistry and Molecular Biology, University of Córdoba, Córdoba, Spain., Alhama J; Maimonides Biomedical Research Institute of Córdoba, Córdoba, Spain.; Department of Biochemistry and Molecular Biology, University of Córdoba, Córdoba, Spain., Romero-Ruiz A; Maimonides Biomedical Research Institute of Córdoba, Córdoba, Spain. b72rorua@uco.es.; Department of Biochemistry and Molecular Biology, University of Córdoba, Córdoba, Spain. b72rorua@uco.es., Arjona-Sánchez Á; Maimonides Biomedical Research Institute of Córdoba, Córdoba, Spain. alvaroarjona@hotmail.com.; Surgical Oncology Unit, Surgery Department, Reina Sofía University Hospital, Córdoba, Spain. alvaroarjona@hotmail.com.
Jazyk: angličtina
Zdroj: Experimental hematology & oncology [Exp Hematol Oncol] 2023 Dec 08; Vol. 12 (1), pp. 102. Date of Electronic Publication: 2023 Dec 08.
DOI: 10.1186/s40164-023-00465-4
Abstrakt: 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 KRAS G12D being the most common subtype. Here, we tested the efficacy of a small-molecule KRAS G12D inhibitor, MRTX1133, in a high-grade PMP xenograft mouse model carrying a KRAS G12D 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 KRAS G12D -PMP tumors and provide a rationale for clinical trials.
(© 2023. The Author(s).)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje