Tumor immunotherapy and targeted therapy, though less toxic than conventional chemotherapy, can increase the risk of thyroid dysfunction. combined with 131-iodine, administered as a radiotherapeutic agent for tumours derived from neural crest cells, can cause primary hypothyroidism. Bexarotene can produce transient central hypothyroidism by altering the feedback effect of thyroid hormone on the pituitary gland. Thyroid dysfunction can be managed in the usual manner without a requirement for dose reduction or discontinuation of the implicated agent. This review aims to highlight the effect of various anticancer agents on thyroid function. Early recognition and appropriate management of thyroid disorders during cancer therapy will help to improve treatment outcomes. strong class=”kwd-title” Keywords: Thyroid, hypothyroidism, anticancer drugs, immune checkpoint inhibitors, tyrosine kinase inhibitors The armamentarium of anticancer drugs available to an oncologist has grown rapidly over the past few decades. The use of cancer immunotherapy and targeted therapy has become more popular in the last few years. It has also become increasingly clear that various anticancer agents, both regular and newer types, may be connected with particular off-target undesireable effects involving the urinary tract, the thyroid gland especially.1 The website of action of popular cancer immunotherapy agents is depicted in em Shape 1 /em . This informative article is targeted at explaining thyroid dysfunction connected with different anticancer agents. These have already been summarised in em Desk 1 /em briefly . It’s important to Rabbit Polyclonal to SENP6 recognize and deal with thyroid dysfunction in such individuals CB-7598 cost appropriately. This can not only enhance their overall standard of living, but also assure ideal treatment result. Open in a separate window Figure 1: Immune pathways and mechanism of action of various cancer immunotherapy agents APC = antigen presenting cell; CD = cluster of differentiation; CTLA-4 = cytotoxic T lymphocyte associated protein-4; IL-2 = interleukin-2; MHC = major histocompatibility complex; PD-1 = programmed cell death protein-1; PD-L1 = programmed death-ligand 1; TCR = T-cell receptor Table 1: Anticancer drugs causing thyroid dysfunction Immune checkpoint inhibitorsHypophysitis (ipilimumab, nivolumab)Primary thyroid dysfunction (ipilimumab, nivolumab, pembrolizumab)Tyrosine kinase inhibitorsHypothyroidism (sunitinib, sorafenib, axitinib, pazopanib, vandetanib, motesanib)Increased levothyroxine requirement in thyrodectomised patients (imatinib, sorafenib, motesanib)Interferon-Hypothyroidism, destructive thyroiditisInterleukin-2HypothyroidismAlemtuzumabGraves diseaseThalidomide analoguesHypothyroidism, ischaemic thyroiditis (thalidomide, lenalidomide)Radioiodine-based cancer therapyHypothyroidism, radiation thyroiditisBexaroteneCentral hypothyroidismConventional agentsAlteration in thyroid binding CB-7598 cost proteins (not clinically relevant) (mitotane, 5-fluorouracil, oestrogens, tamoxifen, podophyllin, L-asparaginase) Open in a separate window Literature search A MEDLINE search was conducted for articles published before 30 April 2019. Articles published in English were considered. The search terms were words related to thyroid disorders, such as thyroid, hypothyroidism, thyrotoxicosis, hyperthyroidism Graves disease central hypothyroidism, and thyroiditis CB-7598 cost in association with anticancer drugs, immune checkpoint inhibitors, tyrosine kinase inhibitors, interferon-, interleukin-2, alemtuzumab, thalidomide, lenalidomide, pomalidomide radioiodine-based cancer therapies and bexarotene. The names of specific drugs, like ipilimumab, nivolumab, pembrolizumab amongst immune check point inhibitors; and sunitinib, sorafenib, axitinib, pazopanib, vandetanib, motesanib, imatinib, cabozantinib, nilotinib, dasatinib, erlotinib, gefitinib, lapatinib, nintedanib, CB-7598 cost regorafenib and tivozanib amongst tyrosine kinase inhibitors, were also included in the search. The abstracts were evaluated for relevance, and full text of all appropriate articles was retrieved. Research lists of selected content articles were searched also. Articles explaining using anticancer agencies for treatment of thyroid cancer were excluded. Immune checkpoint inhibitors A better understanding of the complexities of the human immune system and its regulation paved the way for a novel concept in the field of oncology termed cancer immunotherapy. The basic principle of cancer immunotherapy is usually utilisation of bodys own immune system to target cancer cells. Immune checkpoint substances are regulators from CB-7598 cost the disease fighting capability which offer self-tolerance and stop the disease fighting capability from destroying its cells ( em Body 2 /em ). Included in these are cytotoxic T-lymphocyte linked proteins 4 (CTLA-4) and designed cell death proteins 1 (PD-1; a cell surface area receptor) and its own ligand (PD-L1). CTLA-4 is certainly portrayed on regulatory T cells constitutionally, gets up-regulated on T-cell activation, and functions toward inhibiting another (co-stimulatory) indication for T-cell activation. PD-1 exists on T cells, B cells and organic killer (NK) cells, and binds to PD-L1 portrayed by tumour cells. The interaction between PD-L1 and PD-1 inhibits destruction of tumour cells with the immune system; hence, PD-L1 has ended expressed with the tumour cells with their benefit.2,3 Open up in another window Body 2: Mechanism of action of immune system checkpoint inhibitors APC = antigen presenting cell; CTLA-4 = cytotoxic T lymphocyte linked proteins-4; MHC = main histocompatibility.