Maya B Lodish1. 1. Section on Endocrinology and Genetics, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the Pediatric Endocrinology Inter-Institute Training Program, National Institutes of Health, Bethesda, MD 20892, USA. lodishma@mail.nih.gov
Abstract
CONTEXT: The use of kinase inhibitors (KIs) in the treatment of cancer has become increasingly common, and practitioners must be familiar with endocrine-related side effects associated with these agents. This review provides an update to the clinician regarding the management of potential endocrinological effects of KIs. EVIDENCE ACQUISITION: PubMed was employed to identify relevant manuscripts. A review of the literature was conducted, and data were summarized and incorporated. EVIDENCE SYNTHESIS: KIs, including small molecule KIs and monoclonal antibodies directed against kinases, have emerged over the past decade as an important class of anticancer agents. KIs specifically interfere with signaling pathways that are dysregulated in certain types of cancers and also target common mechanisms of growth, invasion, metastasis, and angiogenesis. Currently, at least 20 KIs are approved as cancer therapeutics. However, KIs may affect a broad spectrum of targets and may have additional, unidentified mechanisms of action at the cellular level due to overlap between signaling pathways in the tumor cell and endocrine system. Recent reports in the literature have identified side effects associated with KIs, including alterations in thyroid function, bone metabolism, linear growth, gonadal function, fetal development, adrenal function, and glucose metabolism. CONCLUSIONS: Clinicians need to monitor the thyroid functions of patients on KIs. In addition, bone density and vitamin D status should be assessed. Special care should be taken to follow linear growth and development in children taking these agents. Clinicians should counsel patients appropriately on the potential adverse effects of KIs on fetal development.
CONTEXT: The use of kinase inhibitors (KIs) in the treatment of cancer has become increasingly common, and practitioners must be familiar with endocrine-related side effects associated with these agents. This review provides an update to the clinician regarding the management of potential endocrinological effects of KIs. EVIDENCE ACQUISITION: PubMed was employed to identify relevant manuscripts. A review of the literature was conducted, and data were summarized and incorporated. EVIDENCE SYNTHESIS: KIs, including small molecule KIs and monoclonal antibodies directed against kinases, have emerged over the past decade as an important class of anticancer agents. KIs specifically interfere with signaling pathways that are dysregulated in certain types of cancers and also target common mechanisms of growth, invasion, metastasis, and angiogenesis. Currently, at least 20 KIs are approved as cancer therapeutics. However, KIs may affect a broad spectrum of targets and may have additional, unidentified mechanisms of action at the cellular level due to overlap between signaling pathways in the tumor cell and endocrine system. Recent reports in the literature have identified side effects associated with KIs, including alterations in thyroid function, bone metabolism, linear growth, gonadal function, fetal development, adrenal function, and glucose metabolism. CONCLUSIONS: Clinicians need to monitor the thyroid functions of patients on KIs. In addition, bone density and vitamin D status should be assessed. Special care should be taken to follow linear growth and development in children taking these agents. Clinicians should counsel patients appropriately on the potential adverse effects of KIs on fetal development.
Authors: Hatem A Azim; Otto Metzger-Filho; Evandro de Azambuja; Sibylle Loibl; Florine Focant; Ekaterina Gresko; Mounir Arfi; Martine Piccart-Gebhart Journal: Breast Cancer Res Treat Date: 2012-02-26 Impact factor: 4.872
Authors: D Neil Hayes; Amy S Lucas; Tawee Tanvetyanon; Monika K Krzyzanowska; Christine H Chung; Barbara A Murphy; Jill Gilbert; Ranee Mehra; Dominic T Moore; Arif Sheikh; Janelle Hoskins; Michele C Hayward; Ni Zhao; Wendi O'Connor; Karen E Weck; Roger B Cohen; Ezra E W Cohen Journal: Clin Cancer Res Date: 2012-01-12 Impact factor: 12.531
Authors: Doreen Braun; Theo D Kim; Philipp le Coutre; Josef Köhrle; Jerome M Hershman; Ulrich Schweizer Journal: J Clin Endocrinol Metab Date: 2011-10-26 Impact factor: 5.958
Authors: M Campone; I Bondarenko; S Brincat; Y Hotko; P N Munster; E Chmielowska; P Fumoleau; R Ward; N Bardy-Bouxin; E Leip; K Turnbull; C Zacharchuk; R J Epstein Journal: Ann Oncol Date: 2011-06-23 Impact factor: 32.976
Authors: John C Araujo; Paul Mathew; Andrew J Armstrong; Edward L Braud; Edwin Posadas; Mathew Lonberg; Gary E Gallick; Géralyn C Trudel; Prashni Paliwal; Shruti Agrawal; Christopher J Logothetis Journal: Cancer Date: 2011-07-25 Impact factor: 6.860
Authors: Samuel A Wells; Bruce G Robinson; Robert F Gagel; Henning Dralle; James A Fagin; Massimo Santoro; Eric Baudin; Rossella Elisei; Barbara Jarzab; James R Vasselli; Jessica Read; Peter Langmuir; Anderson J Ryan; Martin J Schlumberger Journal: J Clin Oncol Date: 2011-10-24 Impact factor: 44.544
Authors: Elin Nyman; Yvonne J W Rozendaal; Gabriel Helmlinger; Bengt Hamrén; Maria C Kjellsson; Peter Strålfors; Natal A W van Riel; Peter Gennemark; Gunnar Cedersund Journal: Interface Focus Date: 2016-04-06 Impact factor: 3.906
Authors: A A Nella; M B Lodish; E Fox; F M Balis; M M Quezado; P O Whitcomb; J Derdak; E Kebebew; B C Widemann; C A Stratakis Journal: J Clin Endocrinol Metab Date: 2014-03-11 Impact factor: 5.958