Cyclin-dependent kinase-9 in B-cell malignancies: pathogenic role and therapeutic implications.
Leuk Lymphoma
; 64(12): 1893-1904, 2023 12.
Article
en En
| MEDLINE
| ID: mdl-37552126
ABSTRACT
Cyclin-dependent kinases (CDK) regulate cell cycle and transcriptional activity. Pan-CDK inhibitors demonstrated early efficacy in lymphoid malignancies, but also have been associated with narrow therapeutic index. Among transcriptional CDKs, CDK7 and CDK9 emerged as promising targets. CDK9 serves as a component of P-TEFb elongation complex and thus is indispensable in mRNA transcription. Selective CDK9 inhibitors demonstrated pre-clinical efficacy in in vitro and in vivo models of B-cell non-Hodgkin lymphoma. CDK9 inhibition results in transcriptional pausing with rapid downmodulation of short-lived oncogenic proteins, e.g. Myc and Mcl-1, followed by cell apoptosis. Early phase clinical trials established safety of CDK9 inhibitors, with manageable neutropenia, infections and gastrointestinal toxicities. In this review, we summarize the rationale of targeting CDK9 in lymphoid malignancies, as well as pre-clinical and early clinical data with pan-CDK and selective CDK9 inhibitors.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Quinasas Ciclina-Dependientes
/
Neoplasias
Límite:
Humans
Idioma:
En
Revista:
Leuk Lymphoma
Asunto de la revista:
HEMATOLOGIA
/
NEOPLASIAS
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos