Medical Oncology Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), IOB-Teknon, Barcelona, Spain.
Oncology Medicine Department, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
Cancer Treat Rev. 2022 May;106:102380. doi: 10.1016/j.ctrv.2022.102380. Epub 2022 Mar 15.
Most malignant thyroid tumours are initially treated with surgery or a combination of surgery and radioactive iodine (RAI) therapy. However, in patients with metastatic disease, many tumours become refractory to RAI, and these patients require alternative treatments, such as locoregional therapies and/or systemic treatment with multikinase inhibitors. Improvements in our understanding of the genetic alterations that occur in thyroid cancer have led to the discovery of several targeted therapies with clinical efficacy. These alterations include NTRK (neurotrophic tyrosine receptor kinase) gene fusions, with the tropomyosin receptor kinase inhibitors larotrectinib and entrectinib both approved by the European Medicines Agency and in other markets worldwide. Inhibitors of aberrant proteins resulting from alterations in RET (rearranged during transfection) and BRAF (B-Raf proto-oncogene) have also shown promising efficacy, and so far have received approval by the US Food and Drug Administration. Selpercatinib, a RET kinase inhibitor, was approved for use in Europe in early 2021. With the discovery of multiple actionable targets, it is imperative that effective testing strategies for these genetic alterations are integrated into the diagnostic armamentarium to ensure that patients who could potentially benefit from targeted treatments are identified. In this review, we offer our recommendations on the optimal testing strategies for detecting genetic alterations in thyroid cancer that have the potential to be targeted by molecular therapy. We also discuss the future of treatments for thyroid cancers, including the use of immune checkpoint inhibitors, and new generations of targeted treatments that are being developed to counter acquired tumour resistance.
大多数恶性甲状腺肿瘤最初采用手术或手术联合放射性碘（RAI）治疗。然而，在转移性疾病患者中，许多肿瘤对 RAI 产生耐药性，这些患者需要替代治疗，如局部区域治疗和/或多激酶抑制剂的全身治疗。我们对甲状腺癌中发生的遗传改变的理解的提高导致了几种具有临床疗效的靶向治疗的发现。这些改变包括 NTRK（神经营养酪氨酸受体激酶）基因融合，神经酪氨酸受体激酶抑制剂拉罗替尼和恩曲替尼已被欧洲药品管理局和世界其他市场批准用于治疗。由于 RET（转染过程中重排）和 BRAF（B-Raf 原癌基因）改变而导致的异常蛋白抑制剂也显示出有希望的疗效，迄今为止已获得美国食品和药物管理局的批准。RET 激酶抑制剂塞尔帕替尼于 2021 年初在欧洲获准使用。随着多个可操作靶点的发现，必须将这些遗传改变的有效检测策略整合到诊断工具中，以确保识别出可能受益于靶向治疗的患者。在这篇综述中，我们就用于检测潜在分子治疗靶点的甲状腺癌遗传改变的最佳检测策略提出了建议。我们还讨论了甲状腺癌治疗的未来，包括免疫检查点抑制剂的使用，以及正在开发用于对抗获得性肿瘤耐药性的新一代靶向治疗。
