Cyclin-dependent Kinases 4/6 Inhibitors in Neuroendocrine Neoplasms: from Bench to Bedside

被引:4
作者
de Sousa, Maria Joao [1 ,2 ]
Gervaso, Lorenzo [2 ,3 ]
Meneses-Medina, Monica Isabel [2 ,4 ]
Spada, Francesca [2 ]
Abdel-Rahman, Omar [5 ,6 ]
Fazio, Nicola [2 ]
机构
[1] IPO Coimbra, Med Oncol Dept, Inst Portugues Oncol Coimbra Francisco Gentil EPE, Coimbra, Portugal
[2] IRCCS, Div Gastrointestinal Med Oncol & Neuroendocrine T, European Inst Oncol, IEO, Via Ripamonti 435, I-20141 Milan, Italy
[3] Univ Pavia, Mol Med Program, Pavia, Italy
[4] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Hematol & Oncol Dept, Mexico City, DF, Mexico
[5] Univ Alberta, Dept Oncol, Edmonton, AB, Canada
[6] Cross Canc Inst, Edmonton, AB, Canada
关键词
Neuroendocrine tumors; CDK4/6; inhibitors; Ribociclib; Palbociclib; Abemaciclib; trilaciclib; SMALL-CELL; TUMORS; EVEROLIMUS; RESISTANCE; MECHANISMS;
D O I
10.1007/s11912-022-01251-x
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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). Summary 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.
引用
收藏
页码:715 / 722
页数:8
相关论文
共 49 条
[1]   Mechanisms of Sensitivity and Resistance to CDK4/6 Inhibition [J].
Alvarez-Fernandez, Monica ;
Malumbres, Marcos .
CANCER CELL, 2020, 37 (04) :514-529
[2]   Phase Ib Dose-escalation/Expansion Trial of Ribociclib in Combination With Everolimus and Exemestane in Postmenopausal Women with HR+, HER2- Advanced Breast Cancer [J].
Bardia, Aditya ;
Modi, Shanu ;
Oliveira, Mafalda ;
Cortes, Javier ;
Campone, Mario ;
Ma, Brigette ;
Dirix, Luc ;
Weise, Amy ;
Hewes, Becker ;
Diaz-Padilla, Ivan ;
Han, Yu ;
Deshpande, Priya ;
Samant, Tanay S. ;
Lorenc, Karen Rodriguez ;
He, Wei ;
Su, Fei ;
Chavez-MacGregor, Mariana .
CLINICAL CANCER RESEARCH, 2020, 26 (24) :6417-6428
[3]   Preclinical Characterization of G1T28: A Novel CDK4/6 Inhibitor for Reduction of Chemotherapy-Induced Myelosuppression [J].
Bisi, John E. ;
Sorrentino, Jessica A. ;
Roberts, Patrick J. ;
Tavares, Francis X. ;
Strum, Jay C. .
MOLECULAR CANCER THERAPEUTICS, 2016, 15 (05) :783-793
[4]   Trilaciclib prior to chemotherapy and atezolizumab in patients with newly diagnosed extensive-stage small cell lung cancer: A multicentre, randomised, double-blind, placebo-controlled Phase II trial [J].
Daniel, Davey ;
Kuchava, Vladimer ;
Bondarenko, Igor ;
Ivashchuk, Oleksandr ;
Reddy, Sreekanth ;
Jaal, Jana ;
Kudaba, Iveta ;
Hart, Lowell ;
Matitashvili, Amiran ;
Pritchett, Yili ;
Morris, Shannon R. ;
Sorrentino, Jessica A. ;
Antal, Joyce M. ;
Goldschmidt, Jerome .
INTERNATIONAL JOURNAL OF CANCER, 2021, 148 (10) :2557-2570
[5]  
Dasari A, 2018, ENETS 2018 C ABSTR
[6]  
Dasari A, 2018, NANETS 2018 S ABSTR
[7]   CDK4/6 Inhibition Augments Antitumor Immunity by Enhancing T-cell Activation [J].
Deng, Jiehui ;
Wang, Eric S. ;
Jenkins, Russell W. ;
Li, Shuai ;
Dries, Ruben ;
Yates, Kathleen ;
Chhabra, Sandeep ;
Huang, Wei ;
Liu, Hongye ;
Aref, Amir R. ;
Ivanova, Elena ;
Paweletz, Cloud P. ;
Bowden, Michaela ;
Zhou, Chensheng W. ;
Herter-Sprie, Grit S. ;
Sorrentino, Jessica A. ;
Bisi, John E. ;
Lizotte, Patrick H. ;
Merlino, Ashley A. ;
Quinn, Max M. ;
Bufe, Lauren E. ;
Yang, Annan ;
Zhang, Yanxi ;
Zhang, Hua ;
Gao, Peng ;
Chen, Ting ;
Cavanaugh, Megan E. ;
Rode, Amanda J. ;
Haines, Eric ;
Roberts, Patrick J. ;
Strum, Jay C. ;
Richards, William G. ;
Lorch, Jochen H. ;
Parangi, Sareh ;
Gunda, Viswanath ;
Boland, Genevieve M. ;
Bueno, Raphael ;
Palakurthi, Sangeetha ;
Freeman, Gordon J. ;
Ritz, Jerome ;
Haining, W. Nicholas ;
Sharpless, Norman E. ;
Arthanari, Haribabu ;
Shapiro, Geoffrey I. ;
Barbie, David A. ;
Gray, Nathanael S. ;
Wong, Kwok-Kin .
CANCER DISCOVERY, 2018, 8 (02) :216-233
[8]   Trilaciclib: First Approval [J].
Dhillon, Sohita .
DRUGS, 2021, 81 (07) :867-874
[9]   Molecular Classification of Neuroendocrine Tumors of the Thymus [J].
Dinter, Helen ;
Bohnenberger, Hanibal ;
Beck, Julia ;
Bornemann-Kolatzki, Kirsten ;
Schuetz, Ekkehard ;
Kueffer, Stefan ;
Klein, Lukas ;
Franks, Teri J. ;
Roden, Anja ;
Emmert, Alexander ;
Hinterthaner, Marc ;
Marino, Mirella ;
Brcic, Luka ;
Popper, Helmut ;
Weis, Cleo-Aron ;
Pelosi, Giuseppe ;
Marx, Alexander ;
Stroebel, Philipp .
JOURNAL OF THORACIC ONCOLOGY, 2019, 14 (08) :1472-1483
[10]   The application and prospect of CDK4/6 inhibitors in malignant solid tumors [J].
Du, Qi ;
Guo, Xiang ;
Wang, Miao ;
Li, Yongfu ;
Sun, Xiaoyi ;
Li, Qin .
JOURNAL OF HEMATOLOGY & ONCOLOGY, 2020, 13 (01)