doi:10.19538/j.cjps.issn1005-2208.2025.09.17

Chinese Journal of Practical Surgery ›› 2025, Vol. 45 ›› Issue (09) : 1050-1055. DOI: 10.19538/j.cjps.issn1005-2208.2025.09.17

Author information +

History +

Abstract

Anaplastic thyroid carcinoma (ATC) is a rare but highly aggressive thyroid malignancy with an extremely poor prognosis, and the median survival time is only 4-6 months. Traditional therapeutic modalities, including surgery, radiotherapy, and chemotherapy, provide limited overall efficacy. With advances in molecular biology, the genomic landscape of ATC has been gradually elucidated. Common alterations include BRAF V600E, TP53 mutations, TERT promoter mutations, and gene fusions involving NTRK, RET, and ALK, affecting signaling pathways such as RAS/RAF/MEK/ERK and PI3K/AKT/mTOR. Targeted therapies against specific alterations (e.g., dabrafenib plus trametinib, larotrectinib, selpercatinib, pralsetinib) have markedly improved survival in selected patients. In the field of immunotherapy, programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors (e.g., spartalizumab, pembrolizumab), administered alone or in combination with targeted therapy or radiotherapy, have shown promising efficacy. Combined immunotherapy and targeted therapy, such as the PD-L1 inhibitor atezolizumab with vemurafenib and cobimetinib, has significantly prolonged survival in patients harboring BRAF V600E mutations. Supportive care, including airway management, nutritional support, and management of adverse effects, remains essential. Multidisciplinary collaboration and individualized precision therapy are central to optimizing ATC management. Future research should focus on mechanisms of resistance and therapeutic strategies for patients without BRAF mutations.

Key words

anaplastic thyroid carcinoma / multimodal therapy / molecular mechanisms / targeted therapy

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

References

［1］ Limaiem F， Kashyap S，Naing PT，et al.Anaplastic thyroid cancer［M］.In: StatPearls ［Internet］. Treasure Island(FL): StatPearls Publishing, 2025.

［2］ Boucai L，Zafereo M，Cabanillas ME.Thyroid cancer: A review［J］.JAMA， 2024，331(5):425-435.DOI:10.1001/jama.2023.28128.

［3］ Maniakas A，Dadu R，Busaidy NL，et al.Evaluation of overall survival in patients with anaplastic thyroid carcinoma，2000-2019［J］.JAMA Oncol，2020，6（9）:1397-1404.DOI:10.1001/jamaoncol.2020.3362.

［4］ Hassan M，Janjua TK，Afridi HK，et al.Anaplastic carcinoma of thyroid gland with widespread soft tissue metastasis: An unusual presentation［J］.BMJ Case Rep，2017，201:7.DOI:10.1136/bcr-2017-220793.

［5］ Forma A，Kłodnicka K，Pająk W，et al.Thyroid cancer: Epidemiology， classification，risk factors， diagnostic and prognostic markers，and current treatment strategies［J］.Int J Mol Sci，2025，26（11）:5173.DOI:10.3390/ijms26115173.

［6］ Wendler J，Kroiss M，Gast K，et al.Clinical presentation，treatment and outcome of anaplastic thyroid carcinoma: Results of a multicenter study in Germany［J］.Eur J Endocrinol，2016，175（6）:521-529.DOI:10.1530/EJE-16-0574.

［7］ Glaser SM，Mandish SF，Gill BS，et al.Anaplastic thyroid cancer: Prognostic factors，patterns of care， and overall survival［J］.Head Neck，2016，38（suppl）:E2083-E2090.DOI:10.1002/hed.24384.

［8］ Grant EG，Tessler FN，Hoang JK，et al.Thyroid ultrasound reporting lexicon: White paper of the ACR thyroid imaging， reporting and data system(TIRADS)committee［J］.J Am Coll Radiol，2015，12（12 Pt A）:1272-1279.DOI:10.1016/j.jacr.2015.07.011.

［9］ Suh HJ，Moon HJ，Kwak JY，et al.Anaplastic thyroid cancer: Ultrasonographic findings and the role of ultrasonography-guided fine needle aspiration biopsy［J］.Yonsei Med J，2013，54（6）:1400-1406.DOI:10.3349/ymj.2013.54.6.1400.

［10］ Alhejaily AG，Alhuzim O，Alwelaie Y.Anaplastic thyroid cancer: Pathogenesis， prognostic factors and genetic landscape(Review)［J］.Mol Clin Oncol，2023，19（6）:99.DOI:10.3892/mco.2023.2695.

［11］ Ferraz C.Molecular testing for thyroid nodules: Where are we now?［J］.Rev Endocr Metab Disord，2024，25（1）:149-159.DOI:10.1007/s11154-023-09842-0.

［12］ Subbiah V，Kreitman RJ，Wainberg ZA，et al.Dabrafenib and trametinib treatment in patients with locally advanced or metastatic BRAF V600-mutant anaplastic thyroid cancer［J］.J Clin Oncol，2018，36（1）:7-13.DOI:10.1200/JCO.2017.73.6785.

［13］ Pan Z，Tan Z，Xu N，et al.Integrative proteogenomic characterization reveals therapeutic targets in poorly differentiated and anaplastic thyroid cancers［J］.Nat Commun，2025，16（1）:3601.DOI:10.1038/s41467-025-58910-3.

［14］ Zeng PYF，Prokopec SD，Lai SY，et al.The genomic and evolutionary landscapes of anaplastic thyroid carcinoma［J］.Cell Rep，2024，43（3）:113826.DOI:10.1016/j.celrep.2024.113826.

［15］ Pozdeyev N，Gay LM，Sokol ES，et al.Genetic analysis of 779 advanced differentiated and anaplastic thyroid cancers［J］.Clin Cancer Res，2018，24（13）:3059-3068.DOI:10.1158/1078-0432.CCR-18-0373.

［16］ Liu R，Xing M.TERT promoter mutations in thyroid cancer［J］.Endocr Relat Cancer，2016，23（3）:R143-155.DOI:10.1530/ERC-15-0533.

［17］ Pozdeyev N，Rose MM，Bowles DW，et al.Molecular therapeutics for anaplastic thyroid cancer［J］.Semin Cancer Biol，2020，61:23-29.DOI:10.1016/j.semcancer.2020.01.005.

［18］ Romano C, Martorana F, Pennisi MS, et al. Opportunities and challenges of liquid biopsy in thyroid cancer［J］. Int J Mol Sci, 2021, 22(14): 7707. DOI:10.3390/ijms22147707.

［19］ Haddad R，Elisei R，Hoff AO，et al.Diagnosis and management of tropomyosin receptor kinase fusion-positive thyroid carcinomas: A review［J］.JAMA Oncol，2023，9（8）:1132-1141.DOI:10.1001/jamaoncol.2023.1379.

［20］ Toda S，Hiroshima Y，Iwasaki H，et al.Genomic landscape and clinical features of advanced thyroid carcinoma: A national database study in Japan［J］.J Clin Endocrinol Metab，2024，109（11）:2784-2792.DOI:10.1210/clinem/dgae271.

［21］ Ferrari SM，Ragusa F，Elia G，et al.Antineoplastic effect of alk inhibitor crizotinib in primary human anaplastic thyroid cancer cells with STRN-ALK fusion in vitro［J］.Int J Mol Sci，2024，25（12）:6734.DOI:10.3390/ijms25126734.

［22］ Boruah M，Agarwal S，Mir RA，et al.Unravelling the reasons behind limited response to anti-PD therapy in ATC: A comprehensive evaluation of tumor-infiltrating immune cells and checkpoints［J］.Endocr Pathol，2024，35（4）:419-431.DOI:10.1007/s12022-024-09832-1.

［23］ Lee NY，Riaz N，Wu V，et al.A pilot study of durvalumab(MEDI4736)with tremelimumab in combination with image-guided stereotactic body radiotherapy in the treatment of metastatic anaplastic thyroid cancer［J］.Thyroid，2022，32（7）:799-806.DOI:10.1089/thy.2022.0050.

［24］ Brignardello E，Palestini N，Felicetti F，et al.Early surgery and survival of patients with anaplastic thyroid carcinoma: Analysis of a case series referred to a single institution between 1999 and 2012［J］.Thyroid，2014，24（11）:1600-1606.DOI:10.1089/thy.2014.0004.

［25］ Yang S，Zhou L，Lu Z，et al.Systematic review with meta-analysis of intraoperative neuromonitoring during thyroidectomy［J］.Int J Surg，2017，39:104-113.DOI:10.1016/j.ijsu.2017.01.086.

［26］ Shi Y，Hsu CC，Robbins JR.Clinical outcomes for unresectable anaplastic thyroid cancer treated with radiation: Impacts of radiation intent and the percentage of life spent receiving treatment［J］.Oral Oncol，2025，167:107447.DOI:10.1016/j.oraloncology.2025.107447.

［27］ Seto A，Sugitani I，Toda K，et al.Chemotherapy for anaplastic thyroid cancer using docetaxel and cisplatin: Report of eight cases［J］.Surg Today，2015，45（2）:221-226.DOI:10.1007/s00595-013-0751-x.

［28］ Kawada K，Kitagawa K，Kamei S，et al.The feasibility study of docetaxel in patients with anaplastic thyroid cancer［J］.Jpn J Clin Oncol，2010，40（6）:596-599.DOI:10.1093/jjco/hyq025.

［29］ Denaro N，Nigro CL，Russi EG，et al.The role of chemotherapy and latest emerging target therapies in anaplastic thyroid cancer［J］.Onco Targets Ther，2013，9:1231-1241.DOI:10.2147/OTT.S46545.

［30］ Bible KC，Kebebew E，Brierley J，et al.2021 American Thyroid Association Guidelines for management of patients with anaplastic thyroid cancer［J］.Thyroid，2021，31（3）:337-386.DOI:10.1089/thy.2020.0944.

［31］ Haddad RI，Bischoff L，Ball D，et al.Thyroid carcinoma，version 2.2022，NCCN clinical practice guidelines in oncology［J］.J Natl Compr Canc Netw，2022，20（8）:925-951.DOI:10.6004/jnccn.2022.0040.

［32］ Subbiah V，Kreitman RJ，Wainberg ZA，et al.Dabrafenib plus trametinib in patients with BRAF V600E-mutant anaplastic thyroid cancer: Updated analysis from the phase Ⅱ ROAR basket study［J］.Ann Oncol，2022，33（4）:406-415.DOI:10.1016/j.annonc.2021.12.014.

［33］ Wang JR，Zafereo ME，Dadu R，et al.Complete surgical resection following neoadjuvant dabrafenib plus trametinib in BRAFV600E-mutated anaplastic thyroid carcinoma［J］.Thyroid，2019，29（8）:1036-1043.DOI:10.1089/thy.2019.0133.

［34］ Tahara M，Kiyota N，Imai H，et al.A phase 2 study of encorafenib in combination with binimetinib in patients with metastatic BRAF-mutated thyroid cancer in Japan［J］.Thyroid，2024，34（4）:467-476.DOI:10.1089/thy.2023.0547.

［35］ Koehler VF，Achterfeld J，Sandner N，et al.NTRK fusion events and targeted treatment of advanced radioiodine refractory thyroid cancer［J］.J Cancer Res Clin Oncol，2023，149（15）:14035-14043.DOI:10.1007/s00432-023-05134-x.

［36］ Wirth LJ，Sherman E，Robinson B，et al.Efficacy of selpercatinib in RET-altered thyroid cancers［J］.N Engl J Med，2020，383（9）:825-835.DOI:10.1056/NEJMoa2005651.

［37］ Subbiah V，Hu MI，Mansfield AS，et al.Pralsetinib in patients with advanced/metastatic rearranged during transfection(RET)-altered thyroid cancer: Updated efficacy and safety data from the ARROW study［J］.Thyroid，2024，34（1）:26-40.DOI:10.1089/thy.2023.0363.

［38］ Aydemirli MD，van Eendenburg JDH，van Wezel T，et al.Targeting EML4-ALK gene fusion variant 3 in thyroid cancer［J］.Endocr Relat Cancer，2021，28（6）:377-389.DOI:10.1530/ERC-20-0436.

［39］ Gui L，Liu S，Zhang Y，et al.A remarkable and durable response to sintilimab and anlotinib in the first-line treatment of an anaplastic thyroid carcinoma without targetable genomic alterations: A case report［J］.Onco Targets Ther，2021，14:2741-2746.DOI:10.2147/OTT.S305196.

［40］ Kiyota N，Koyama T，Sugitani I.Anticancer drug therapy for anaplastic thyroid cancer［J］.Eur Thyroid J，2025，14（2）:e240287.DOI:10.1530/ETJ-24-0287.

［41］ Nakajima EC，Drezner N，Li X，et al.FDA approval summary: Sotorasib for kras g12c-mutated metastatic NSCLC［J］.Clin Cancer Res，2022，28（8）:1482-1486.DOI:10.1158/1078-0432.CCR-21-3074.

［42］ Jänne PA，Riely GJ，Gadgeel SM，et al.Adagrasib in non-small-cell lung cancer harboring a KRASG12C mutation［J］.N Engl J Med，2022，387（2）:120-131.DOI:10.1056/NEJMoa2204619.

［43］ Wang P，Sun X，He X，et al.Glecirasib，a potent and selective covalent KRAS G12C inhibitor exhibiting synergism with cetuximab or SHP2 inhibitor JAB-3312［J］.Cancer Res Commun，2025，5（5）:792-803.DOI:10.1158/2767-9764.CRC-25-0001.

［44］ Toda S，Sato S，Saito N，et al.TROP-2，nectin-4，GPNMB，and B7-H3 are potentially therapeutic targets for anaplastic thyroid carcinoma［J］.Cancers(Basel)，2022，14（3）:579.DOI:10.3390/cancers14030579.

［45］ Chen CP，Lin SF，Yeh CN，et al.Synergistic effects of the combination of trametinib and alpelisib in anaplastic thyroid cancer with BRAF and PI3KCA co-mutations［J］.Heliyon，2024，10（7）:e29055.DOI:10.1016/j.heliyon.2024.e29055.

［46］ Capdevila J，Wirth LJ，Ernst T，et al.PD-1 blockade in anaplastic thyroid carcinoma［J］.J Clin Oncol，2020，38（23）:2620-2627.DOI:10.1200/JCO.19.02727.

［47］ Iyer PC，Dadu R，Gule-Monroe M，et al.Salvage pembrolizumab added to kinase inhibitor therapy for the treatment of anaplastic thyroid carcinoma［J］.J Immunother Cancer，2018，6（1）:68.DOI:10.1186/s40425-018-0378-y.

［48］ Sehgal K，Pappa T，Shin KY，et al.Dual immune checkpoint inhibition in patients with aggressive thyroid carcinoma: A phase 2 nonrandomized clinical trial［J］.JAMA Oncol，2024，10（12）:1663-1671.DOI:10.1001/jamaoncol.2024.4019.

［49］ Chintakuntlawar AV，Yin J，Foote RL，et al.A phase 2 study of pembrolizumab combined with chemoradiotherapy as initial treatment for anaplastic thyroid cancer［J］.Thyroid，2019，29（11）:1615-1622.DOI:10.1089/thy.2019.0086.

［50］ Dierks C，Seufert J，Aumann K，et al.Combination of lenvatinib and pembrolizumab is an effective treatment option for anaplastic and poorly differentiated thyroid carcinoma［J］.Thyroid，2021，31（7）:1076-1085.DOI:10.1089/thy.2020.0322.

［51］ Cabanillas ME，Dadu R，Ferrarotto R，et al.Anti-programmed death ligand 1 plus targeted therapy in anaplastic thyroid carcinoma: A nonrandomized clinical trial［J］.JAMA Oncol，2024，10（12）:1672-1680.DOI:10.1001/jamaoncol.2024.4729.

［52］ Moyer KF，Marcadis AR，Shaha AR.Airway management， symptom relief and best supportive care in anaplastic thyroid cancer［J］.Curr Opin Otolaryngol Head Neck Surg，2020，28（2）:74-78.DOI:10.1097/MOO.0000000000000619.

［53］ Agate L，Minaldi E，Basolo A，et al.Nutrition in advanced thyroid cancer patients［J］.Nutrients，2022，14（6）:1298.DOI:10.3390/nu14061298.

［54］ Schneider BJ，Naidoo J，Santomasso BD，et al.Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: ASCO guideline update［J］.J Clin Oncol，2021，39（36）:4073-4126.DOI:10.1200/JCO.21.01440.

［55］ Morrison LJ，Morrison RS. Palliative care and pain management［J］. Med Clin North Am， 2006，90(5):983-1004.DOI:10.1016/j.mcna.2006.05.010.

［56］张大林, 董文武, 张浩. 2024年版日本《甲状腺肿瘤诊疗指南》外科治疗部分更新解读［J］. 中国实用外科杂志, 2025, 45(1): 42-47. DOI:10.19538/j.cjps.issn1005-2208.2025.01.06.