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Front. Oncol. | doi: 10.3389/fonc.2018.00608

CDK 4/6 inhibitors as single agent in advanced solid tumors

 Francesco Schettini1*,  Irene De Santo1, Carmen G. Rea1, Pietro De Placido1,  Luigi Formisano1, Mario Giuliano1, 2, Grazia Arpino1, Michelino De Laurentiis3,  Fabio Puglisi4, 5, Sabino De Placido1 and Lucia Del Mastro6, 7
  • 1University of Naples Federico II, Italy
  • 2Baylor College of Medicine, United States
  • 3Istituto Nazionale Tumori Fondazione G. Pascale (IRCCS), Italy
  • 4Dipartimento di Area medica, Università degli Studi di Udine, Italy
  • 5Centro di Riferimento Oncologico di Aviano (IRCCS), Italy
  • 6Ospedale San Martino (IRCCS), Italy
  • 7Università di Genova, Italy

Cyclin-dependent kinases (CDK) 4/6 inhibitors, namely abemaciclib, palbociclib and ribociclib, interfere with cell cycle progression, induce cell senescence and might promote cancer cell disruption by a cytotoxic T cells-mediated effect. Phase III randomized clinical trials have proven that CDK4/6 inhibitors (CDK4/6i) in combination with several endocrine agents improve treatment efficacy over endocrine agents alone for hormone receptor positive (HR+) HER2 negative (HER2-) metastatic breast cancer (MBC). Based on such results, these combinations have been approved for clinical use. Preclinical studies in cell cultures and mouse models proved that CDK4/6i are active against a broad spectrum of solid tumors other than breast cancer, including liposarcoma, rhabdomyosarcoma, non-small cell lung cancer, glioblastoma multiforme, esophageal cancer and melanoma. The role of CDK4/6i in monotherapy in several solid tumors is currently under evaluation in phase I, II and III trials. Nowadays, abemaciclib is the only of the three inhibitors that has received approval as single agent therapy for pretreated HR+ HER2- MBC. Here we review biological, preclinical and clinical data on the role of CDK4/6 inhibitors as single agents in advanced solid tumors.

Keywords: solid tumors, Cyclin-Dependent Kinases, Palbociclib, Ribociclib, Abemaciclib, Cell Cycle

Received: 26 Oct 2018; Accepted: 28 Nov 2018.

Edited by:

Yunkai Zhang, Vanderbilt University Medical Center, United States

Reviewed by:

Zhenfang Du, Vanderbilt University Medical Center, United States
Mao Wang, Memorial Sloan Kettering Cancer Center, United States
Junyi Li, University of Pittsburgh, United States  

Copyright: © 2018 Schettini, De Santo, Rea, De Placido, Formisano, Giuliano, Arpino, De Laurentiis, Puglisi, De Placido and Del Mastro. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Francesco Schettini, University of Naples Federico II, Napoli, Italy, francescoschettini1987@gmail.com