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复发性/转移性间变性甲状腺癌的有前途的治疗靶点。

Promising Therapeutic Targets for Recurrent/Metastatic Anaplastic Thyroid Cancer.

机构信息

Department of Internal Medicine, AdventHealth, Sebring, Florida, USA.

Department of Pathology, Stanford University, Stanford, CA, USA.

出版信息

Curr Treat Options Oncol. 2024 Jul;25(7):869-884. doi: 10.1007/s11864-024-01219-y. Epub 2024 Jun 12.

Abstract

Anaplastic thyroid cancer presents formidable challenges, particularly in cases of recurrence or metastasis. Timely BRAF V600E testing is imperative at diagnosis, initially through immunohistochemistry, followed by comprehensive genomic profiling encompassing genes such as NTRK, RET, ALK, and assessment of tumor mutation burden (TMB). FDA-approved treatment options include dabrafenib and trametinib for patients with BRAF mutations, while those exhibiting high TMB may benefit from pembrolizumab. Further therapeutic decisions hinge upon mutational profile, urgency of response required, airway integrity, and access to targeted therapies There is growing use of immunotherapy for ATC based on published reports of activity, but currently there is no FDA approved agent for ATC. The off-label utilization of "precision medicine" combinations imposes a considerable financial strain, underscoring the necessity for further clinical trials to elucidate promising therapeutic avenues for this orphan disease. There is a pressing need for the development and support of clinical trials investigating genomically driven and immune-based therapies for anaplastic thyroid cancer.

摘要

间变性甲状腺癌带来了巨大的挑战,尤其是在复发或转移的情况下。在诊断时,及时进行 BRAF V600E 检测至关重要,最初通过免疫组织化学检测,然后进行全面的基因组分析,包括 NTRK、RET、ALK 等基因,并评估肿瘤突变负荷(TMB)。美国食品和药物管理局批准的治疗选择包括达拉非尼和曲美替尼用于 BRAF 突变患者,而那些 TMB 较高的患者可能受益于 pembrolizumab。进一步的治疗决策取决于突变谱、所需的反应紧迫性、气道完整性和获得靶向治疗的机会。基于已发表的活性报告,间变性甲状腺癌越来越多地使用免疫疗法,但目前尚无美国食品和药物管理局批准的间变性甲状腺癌治疗药物。“精准医学”联合用药的非标签使用给患者带来了相当大的经济压力,强调了需要进一步进行临床试验,以阐明针对这种孤儿病的有前途的治疗途径。迫切需要开发和支持临床试验,以研究针对间变性甲状腺癌的基于基因组和免疫的治疗方法。

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