Endocrine side effects of broad-acting kinase inhibitors

    1. Constantine A Stratakis1,2
    1. 1Section on Endocrinology Genetics, Program on Developmental Endocrinology Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
      2Pediatric Endocrinology Inter-Institute Training Program, National Institutes of Health (NIH), 10 Center Drive, CRC Room 1-3330, Bethesda, Maryland 20892, USA
    1. (Correspondence should be addressed to M B Lodish at 10 Center Drive, CRC Room 1-3330, Bethesda, Maryland 20892, USA; Email: lodishma{at}mail.nih.gov)

    Abstract

    Targeted therapy in oncology consists of drugs that specifically interfere with abnormal signaling pathways that are dysregulated in cancer cells. Tyrosine kinase inhibitors (TKIs) take advantage of unique oncogenes that are activated in certain types of cancer, and also target common mechanisms of growth, invasion, metastasis, and angiogenesis. However, many kinase inhibitors for cancer therapy are somewhat nonselective, and most have additional mechanisms of action at the cellular level, which are not completely understood. The use of these agents has increased our knowledge of important side effects, of which the practicing clinician must be aware. Recently, proposed endocrine-related side effects of these agents include alterations in thyroid function, bone metabolism, linear growth, gonadal function, fetal development, and glucose metabolism, and adrenal function. This review summarizes the most recent data on the endocrine side effects of TKIs.

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