CDK 4/6 Inhibitors as Single Agent in Advanced Solid Tumors

Francesco Schettini, Irene De Santo, Carmen G Rea, Pietro De Placido, Luigi Formisano, Mario Giuliano, Grazia Arpino, Michelino De Laurentiis, Fabio Puglisi, Sabino De Placido, Lucia Del Mastro

Research output: Contribution to journalReview article

Abstract

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.

Original languageEnglish
Article number608
Number of pages12
JournalFrontiers in Oncology
Volume8
DOIs
Publication statusPublished - 2018

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Cyclin-Dependent Kinase 6
Cyclin-Dependent Kinase 4
Breast Neoplasms
Neoplasms
Liposarcoma
Phase III Clinical Trials
Rhabdomyosarcoma
Cell Aging
Glioblastoma
Esophageal Neoplasms
Non-Small Cell Lung Carcinoma
Melanoma
Cell Cycle
Randomized Controlled Trials
Cell Culture Techniques
Hormones
T-Lymphocytes

Cite this

Schettini, F., De Santo, I., Rea, C. G., De Placido, P., Formisano, L., Giuliano, M., ... Del Mastro, L. (2018). CDK 4/6 Inhibitors as Single Agent in Advanced Solid Tumors. Frontiers in Oncology, 8, [608]. https://doi.org/10.3389/fonc.2018.00608

CDK 4/6 Inhibitors as Single Agent in Advanced Solid Tumors. / Schettini, Francesco; De Santo, Irene; Rea, Carmen G; De Placido, Pietro; Formisano, Luigi; Giuliano, Mario; Arpino, Grazia; De Laurentiis, Michelino; Puglisi, Fabio; De Placido, Sabino; Del Mastro, Lucia.

In: Frontiers in Oncology, Vol. 8, 608, 2018.

Research output: Contribution to journalReview article

Schettini, F, De Santo, I, Rea, CG, De Placido, P, Formisano, L, Giuliano, M, Arpino, G, De Laurentiis, M, Puglisi, F, De Placido, S & Del Mastro, L 2018, 'CDK 4/6 Inhibitors as Single Agent in Advanced Solid Tumors', Frontiers in Oncology, vol. 8, 608. https://doi.org/10.3389/fonc.2018.00608
Schettini F, De Santo I, Rea CG, De Placido P, Formisano L, Giuliano M et al. CDK 4/6 Inhibitors as Single Agent in Advanced Solid Tumors. Frontiers in Oncology. 2018;8. 608. https://doi.org/10.3389/fonc.2018.00608
Schettini, Francesco ; De Santo, Irene ; Rea, Carmen G ; De Placido, Pietro ; Formisano, Luigi ; Giuliano, Mario ; Arpino, Grazia ; De Laurentiis, Michelino ; Puglisi, Fabio ; De Placido, Sabino ; Del Mastro, Lucia. / CDK 4/6 Inhibitors as Single Agent in Advanced Solid Tumors. In: Frontiers in Oncology. 2018 ; Vol. 8.
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AU - Giuliano, Mario

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AB - 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.

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