Thyroid Cancer in the Modern Era: From Molecular Landscape and Multimodal Diagnostics to Integrative Traditional Chinese Medicine—A Comprehensive Review

Yingqi Xiong,1 Yaxin Hu,2 Manya Wang,3 Xin Xiong,4 Haishen Zhao31Traditional Chinese Medicine Department, Nanjing West Road Street Community Health Service Center, Shanghai, People’s Republic of China; 2Traditional Chinese Medicine Department, Qingdao Special Servicemen Recuperation Center of PLA Navy, Qingdao, Shandong, People’s Republic of China; 3Department of Rehabilitation Medicine, Nanhui Xincheng Town Community Health Service Center, Shanghai, People’s Republic of China; 4Graduate School, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, People’s Republic of ChinaCorrespondence: Xin Xiong, Graduate School, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, People’s Republic of China, Email hljzylsj@126.com Haishen Zhao, Department of Rehabilitation Medicine, Nanhui Xincheng Town Community Health Service Center, Shanghai, People’s Republic of China, Email zhaohaishen666@126.comAbstract: In recent decades, the global incidence of thyroid cancer has risen sharply mainly due to the high detection rate of papillary thyroid microcarcinoma and overdiagnosis, with its overall mortality staying steady. Classic pathogenic drivers encompass childhood radiation exposure, iodine disorder, and hallmark gene alterations including BRAF V600E, RET/PTC, RAS and PAX8/PPARγ. Modern multimodal diagnostic systems integrating artificial intelligence-assisted high-resolution ultrasound, Thyroseq-V2, Afirma, circulating tumor DNA detection and refined pathological examination achieve precise preoperative stratification. Aberrant activation of MAPK/ERK, PI3K/AKT and Wnt/β-catenin cascades, coupled with an immune-suppressive tumor microenvironment dominated by M2-type tumor-associated macrophages, regulatory T cells and PD-L1 overexpression, drives thyroid cancer progression and dedifferentiation. Current comprehensive integrated therapeutic strategies cover robotic surgery, radioactive iodine ablation, external radiotherapy, molecular targeted drugs (sorafenib, lenvatinib, vemurafenib combined with trametinib) and novel immunotherapy. Traditional Chinese Medicine (TCM), based on the TCM pathogenesis of liver qi stagnation, phlegm-blood stasis and qi-blood deficiency for goiter, serves as an adjuvant therapy for thyroid cancer. Active ingredients such as honokiol, artesunate, ginsenoside Rg3, astragalus polysaccharide and curcumin can suppress tumor proliferation, reshape anti-tumor immunity and inhibit metastasis via regulating reactive oxygen species, PI3K/AKT pathway, epithelial–mesenchymal transition and matrix metalloproteinases. Existing clinical observations confirm that TCM can relieve clinical discomfort, improve life quality and lower recurrence risk when combined with conventional radioiodine or anti-tumor treatment. However, the clinical application of TCM for thyroid cancer is greatly restricted by insufficient syndrome differentiation standardization, low-quality clinical evidence and unclear herbal safety risks. Most available studies are small-sample retrospective analyses lacking large-scale, multicenter randomized controlled trials to verify efficacy and safety. Future research should focus on standardized clinical trial design, in-depth pharmacological mechanism exploration, and construction of standardized thyroid cancer integrative diagnosis and treatment regimens combining Western precision therapy and TCM adjuvant intervention, to clarify the definite positioning of TCM in whole-course thyroid cancer management.Keywords: thyroid cancer, BRAF V600E, tumor microenvironment, targeted therapy, traditional Chinese medicine, immunomodulation, overdiagnosis, multimodal imaging