Dysregulation of the cell cycle is a hallmark of cancer that leads to aberrant cellular proliferation. CDK4/6 are cyclin-dependent kinases activated in response to proliferative signaling, which induce RB hyper-phosphorylation and hence activation of E2F transcription factors, thus promoting cell cycle progression through the S phase. Pharmacologic inhibition of CDK4/6 by palbociclib, ribociclib, or abemaciclib has been showing promising activity in multiple cancers with the best results achieved in combination with other agents. Indeed, CDK4/6 inhibitors are currently approved in combination with endocrine therapy for the treatment of estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced or metastatic breast cancer. Moreover, a number of clinical trials are currently underway to test the efficacy of combining CDK4/6 inhibitors with different drugs not only in breast but also in other types of cancer. Beyond the inhibition of cell proliferation, CDK4/6 inhibitors have recently revealed new effects on cancer cells and on tumor microenvironment. In particular, it has been reported that these agents induce a senescent-like phenotype, impact on cell metabolism and exert both immunomodulatory and immunogenic effects. Here we describe recent data on the anti-tumor effects of CDK4/6 inhibitors as single agents or in combined therapies, focusing in particular on their metabolic and immunomodulatory activities.

Multiple effects of CDK4/6 inhibition in cancer: From cell cycle arrest to immunomodulation / Bonelli, M.; La Monica, S.; Fumarola, C.; Alfieri, R.. - In: BIOCHEMICAL PHARMACOLOGY. - ISSN 0006-2952. - 170:(2019), p. 113676. [10.1016/j.bcp.2019.113676]

Multiple effects of CDK4/6 inhibition in cancer: From cell cycle arrest to immunomodulation

Bonelli M.;La Monica S.;Fumarola C.;Alfieri R.
2019-01-01

Abstract

Dysregulation of the cell cycle is a hallmark of cancer that leads to aberrant cellular proliferation. CDK4/6 are cyclin-dependent kinases activated in response to proliferative signaling, which induce RB hyper-phosphorylation and hence activation of E2F transcription factors, thus promoting cell cycle progression through the S phase. Pharmacologic inhibition of CDK4/6 by palbociclib, ribociclib, or abemaciclib has been showing promising activity in multiple cancers with the best results achieved in combination with other agents. Indeed, CDK4/6 inhibitors are currently approved in combination with endocrine therapy for the treatment of estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced or metastatic breast cancer. Moreover, a number of clinical trials are currently underway to test the efficacy of combining CDK4/6 inhibitors with different drugs not only in breast but also in other types of cancer. Beyond the inhibition of cell proliferation, CDK4/6 inhibitors have recently revealed new effects on cancer cells and on tumor microenvironment. In particular, it has been reported that these agents induce a senescent-like phenotype, impact on cell metabolism and exert both immunomodulatory and immunogenic effects. Here we describe recent data on the anti-tumor effects of CDK4/6 inhibitors as single agents or in combined therapies, focusing in particular on their metabolic and immunomodulatory activities.
2019
Multiple effects of CDK4/6 inhibition in cancer: From cell cycle arrest to immunomodulation / Bonelli, M.; La Monica, S.; Fumarola, C.; Alfieri, R.. - In: BIOCHEMICAL PHARMACOLOGY. - ISSN 0006-2952. - 170:(2019), p. 113676. [10.1016/j.bcp.2019.113676]
File in questo prodotto:
File Dimensione Formato  
BCP_113676_edit_report.pdf

accesso aperto

Tipologia: Documento in Post-print
Licenza: Creative commons
Dimensione 738.59 kB
Formato Adobe PDF
738.59 kB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2866247
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 56
  • ???jsp.display-item.citation.isi??? 55
social impact