從腫瘤轉移機轉談甲狀腺未分化癌藥物治療之進展

The Mechanism of Cancer Metastasis and Advances in Potential Treatment for Anaplastic Thyroid Cancer

花士哲(Shih-Che Hua) ； 盧介祥(Chieh-Hsiang Lu) ； 張天鈞(Tien-Chun Chang)

《內科學誌》 19卷6期 (2008/12) Pp. 472-480

https://doi.org/10.6314/JIMT.2008.19(6).04

摘要

絕大多數癌症是死於轉移而非腫瘤本身，因此瞭解轉移的機轉是現今很重要的研究課題。早在十九世紀，有一位Paget學者，提出一個種子與土壤的假說(seed and soil hypothesis)來解釋轉移現象，即擴散的癌細胞如種子，必須有適合其生長的特殊土壤（目標器官），才能成功順利地長成而轉移腫瘤。癌細胞病理上，猶如寄生蟲，需要依賴並利用宿主環境，才能自我存活。腫瘤爲了成功轉移，本身會運用各種策略，除了血管新生作用之外，還有其它機轉，比如由上皮細胞轉型成間質細胞(epitheilial-to-mesenchymal transition, EMT)以更具移行力和侵犯力，也能適應各種不同環境轉換不同細胞形態的高度可塑能力。而腫瘤與其所處的宿主微環境(microenviorment)，包括纖維母細胞、免疫細胞和胞外間質等，都有緊密的交互作用，也會決定並影響腫瘤轉移的進程。關於癌細胞爲什麼會轉移到特定的目標器官，近來有研究證據支持細胞激素及其對應受體，類似發炎機轉的理論。也有研究提出癌症幹細胞的觀念。甲狀腺未分化癌爲一有高轉移率與死亡率的癌症，傳統的治療方式包括手術、放射線治療、化學治療或其合併治療，效果非常不理想，病患經診斷後平均只能存活三個月。透過對於癌轉移機轉的更多認識，現在有許多分子標靶的藥物研究進行中，在人體試驗上的效果令人期待。

關鍵字

癌症轉移 ； 機轉 ； 甲狀腺未分化癌 ； 標靶療法

並列摘要

Most cancer deaths are caused by metastasis rather than the primary tumor. Therefore, nowadays, it is crucial to understand the mechanism of metastasis more and more. Early in the nineteenth century, Paget postulated the ”seed and soil” theory to explain the phenomenon: the disseminating cancer cells (”seed”) need to find the appropriate microenviorment in target organs (”soil”) for metastatic growth. Pathologically, as parasites, the cancer cells exploit the host and survive depending on the host environment. Cancer cells can use multiple strategies to metastasize successfully. Besides angiogenesis, other mechanisms exemplified as epithelial-tomesenchymal transition (EMT) making cells more migratory and invasive, and exhibiting marked cell plasticity for adaptive switch in different host environment. There is also a close crosstalk and interaction between cancer cells and the host microenvironment (including fibroblasts, immune cells, and extracelluar matrix). The interaction will determine and influence the progression of cancer at all stages. Regarding why cancer cells would metastasize to the specified distant organ, recently, there are emerging evidences supporting the chemoattraction theory (the attraction between cytokines and its corresponding receptors), as the mechanism of inflammation. There are also accumulating evidences supporting the concept of cancer stem cells. Anaplastic thyroid cancer (ATC) has very high metastasis and mortality rates among all human cancers. Conventional treatments for ATC include surgery, radiation therapy, chemotherapy, or their combination. Current treatment results are very disappointing and the patients' average survival period is only three months after establishing diagnosis. Recently, because of the better understanding the mechanism of metastasis, there are various potential target therapy medicines for ATC conducted in vitro or in vivo experiments. The future clinical trial results may be promising.

並列關鍵字

Cancer metastasis ； Mechanism ； Anaplastic thyroid cancer ； ATC ； Target therapy