MYC and KRAS cooperation : from historical challenges to therapeutic opportunities in cancer
Casacuberta-Serra, Sílvia (Peptomyc S.L.)
González-Larreategui, Íñigo (Vall d'Hebron Institut d'Oncologia)
Capitán-Leo, Daniel (Vall d'Hebron Institut d'Oncologia)
Soucek, Laura (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Fecha:	2024
Resumen:	RAS and MYC rank amongst the most commonly altered oncogenes in cancer, with RAS being the most frequently mutated and MYC the most amplified. The cooperative interplay between RAS and MYC constitutes a complex and multifaceted phenomenon, profoundly influencing tumor development. Together and individually, these two oncogenes regulate most, if not all, hallmarks of cancer, including cell death escape, replicative immortality, tumor-associated angiogenesis, cell invasion and metastasis, metabolic adaptation, and immune evasion. Due to their frequent alteration and role in tumorigenesis, MYC and RAS emerge as highly appealing targets in cancer therapy. However, due to their complex nature, both oncogenes have been long considered "undruggable" and, until recently, no drugs directly targeting them had reached the clinic. This review aims to shed light on their complex partnership, with special attention to their active collaboration in fostering an immunosuppressive milieu and driving immunotherapeutic resistance in cancer. Within this review, we also present an update on the different inhibitors targeting RAS and MYC currently undergoing clinical trials, along with their clinical outcomes and the different combination strategies being explored to overcome drug resistance. This recent clinical development suggests a paradigm shift in the long-standing belief of RAS and MYC "undruggability", hinting at a new era in their therapeutic targeting.
Ayudas:	Agencia Estatal de Investigación PLEC2021-007959 European Commission 101142260 Fundació la Marató de TV3 2019429 Agencia Estatal de Investigación FPU20/04812 Agencia Estatal de Investigación CEX2020-001024-S
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Oncogenes ; Cancer therapy
Publicado en:	Signal Transduction and Targeted Therapy, Vol. 9 (August 2024) , art. 205, ISSN 2059-3635

DOI: 10.1038/s41392-024-01907-z
PMID: 39164274

30 p, 4.5 MB

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