The role of CRAF in cancer progression: from molecular mechanisms to precision therapies.

Autor: Riaud M; Gerald Bronfman Department of Oncology, McGill University, Montreal, Quebec, Canada.; Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada., Maxwell J; Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada.; Division of Experimental Medicine, Faculty of Medicine, McGill University, Montreal, Quebec, Canada., Soria-Bretones I; Gerald Bronfman Department of Oncology, McGill University, Montreal, Quebec, Canada.; Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada.; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada., Dankner M; Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada.; Faculty of Medicine, McGill University, Montreal, Quebec, Canada.; Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada., Li M; Gerald Bronfman Department of Oncology, McGill University, Montreal, Quebec, Canada., Rose AAN; Gerald Bronfman Department of Oncology, McGill University, Montreal, Quebec, Canada. april.rose@mcgill.ca.; Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada. april.rose@mcgill.ca.; Division of Experimental Medicine, Faculty of Medicine, McGill University, Montreal, Quebec, Canada. april.rose@mcgill.ca.
Jazyk: angličtina
Zdroj: Nature reviews. Cancer [Nat Rev Cancer] 2024 Feb; Vol. 24 (2), pp. 105-122. Date of Electronic Publication: 2024 Jan 09.
DOI: 10.1038/s41568-023-00650-x
Abstrakt: The RAF family of kinases includes key activators of the pro-tumourigenic mitogen-activated protein kinase pathway. Hyperactivation of RAF proteins, particularly BRAF and CRAF, drives tumour progression and drug resistance in many types of cancer. Although BRAF is the most studied RAF protein, partially owing to its high mutation incidence in melanoma, the role of CRAF in tumourigenesis and drug resistance is becoming increasingly clinically relevant. Here, we summarize the main known regulatory mechanisms and gene alterations that contribute to CRAF activity, highlighting the different oncogenic roles of CRAF, and categorize RAF1 (CRAF) mutations according to the effect on kinase activity. Additionally, we emphasize the effect that CRAF alterations may have on drug resistance and how precision therapies could effectively target CRAF-dependent tumours. Here, we discuss preclinical and clinical findings that may lead to improved treatments for all types of oncogenic RAF1 alterations in cancer.
(© 2024. Springer Nature Limited.)
Databáze: MEDLINE
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