Maria João de Sousa1,2, Lorenzo Gervaso2,3, Monica Isabel Meneses-Medina2,4, Francesca Spada2, Omar Abdel-Rahman5, Nicola Fazio6. 1. Medical Oncology Department, Instituto Português de Oncologia de Coimbra Francisco Gentil EPE, IPO Coimbra, Coimbra, Portugal. 2. Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Via Ripamonti 43520141, Milan, Italy. 3. Molecular Medicine Program, University of Pavia, Pavia, Italy. 4. Hematology and Oncology Department, Instituto Nacional de Ciencias Médicas Y Nutrición Salvador Zubirán, Mexico City, Mexico. 5. Department of Oncology, University of Alberta and Cross Cancer Institute, Edmonton, AB, Canada. 6. Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Via Ripamonti 43520141, Milan, Italy. nicola.fazio@ieo.it.
Abstract
PURPOSE OF REVIEW: Cyclin-dependent kinases (CDKs) are key regulators that play an important role in cell division. Palbociclib, ribociclib and abemaciclib showed significant antitumor activity in several malignancies and, recently, also a myeloprotective effect for trilaciclib when added to chemotherapy. The purpose of this review is to highlight the current evidence for CDK4/6 inhibitors in neuroendocrine neoplasms (NENs). RECENT FINDINGS: Preclinical results showed a promising antitumor activity of CDK4/6 inhibitors in neuroendocrine tumors (NETs), but so far, the very few small clinical trials did not show a strong impact on progression free survival (PFS) and objective response in NETs. Meanwhile, the CDK4/6 inhibitor trilaciclib revealed significant effects in reducing chemotherapy-induced myelosuppression in small cell lung cancer (SCLC). Up to date, CDK4/6 inhibitors are still considered investigational in NETs as antitumor agents, whereas trilaciclib can be used in the routine clinical practice in extensive stage SCLC patients for reducing myelotoxicity of standard chemotherapy.
PURPOSE OF REVIEW: Cyclin-dependent kinases (CDKs) are key regulators that play an important role in cell division. Palbociclib, ribociclib and abemaciclib showed significant antitumor activity in several malignancies and, recently, also a myeloprotective effect for trilaciclib when added to chemotherapy. The purpose of this review is to highlight the current evidence for CDK4/6 inhibitors in neuroendocrine neoplasms (NENs). RECENT FINDINGS: Preclinical results showed a promising antitumor activity of CDK4/6 inhibitors in neuroendocrine tumors (NETs), but so far, the very few small clinical trials did not show a strong impact on progression free survival (PFS) and objective response in NETs. Meanwhile, the CDK4/6 inhibitor trilaciclib revealed significant effects in reducing chemotherapy-induced myelosuppression in small cell lung cancer (SCLC). Up to date, CDK4/6 inhibitors are still considered investigational in NETs as antitumor agents, whereas trilaciclib can be used in the routine clinical practice in extensive stage SCLC patients for reducing myelotoxicity of standard chemotherapy.
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