Arrested Developments: CDK4/6 Inhibitor Resistance and Alterations in the Tumor Immune Microenvironment.
Clin Cancer Res
; 25(3): 921-927, 2019 02 01.
Article
em En
| MEDLINE
| ID: mdl-30287548
ABSTRACT
The uncontrolled proliferation of cancer cells has led to the development of small-molecule inhibitors to target cell-cycle progression. Palbociclib, ribociclib, and abemaciclib are ATP-competitive inhibitors of cyclin-dependent kinases 4/6 (CDK4/6), which function early within the G1 phase of the cell cycle. Recently, CDK4/6 inhibitors have gained FDA approval in postmenopausal estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer and testing in other cancer types is underway. However, resistance to CDK4/6 inhibitors frequently develops. In addition, targeting CDK4/6 may augment the action of immune checkpoint blockade agents. Here, we review recent studies that provide the preclinical rationale for treatment combinations and schedules that include CDK4/6 inhibitors. Furthermore, we discuss inhibitor effects on tumor-infiltrating lymphocytes as a preclinical rationale for targeting CDK4/6 in combination with anti-PD-1 or anti-CTLA-4 antibodies.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Resistencia a Medicamentos Antineoplásicos
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Inibidores de Proteínas Quinases
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Quinase 4 Dependente de Ciclina
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Quinase 6 Dependente de Ciclina
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Microambiente Tumoral
Idioma:
En
Revista:
Clin Cancer Res
Ano de publicação:
2019
Tipo de documento:
Article