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| Title: | 由數學模型討論有抗藥性風險下長期使用節拍式化療治療癌症之可行性
Investigate the Feasibility of Treating Cancer with Long-Term Metronomic Chemotherapy under the Risk of Resistance with a Mathematical Modeling Approach |
| Authors: | 陳政輝 |
| Contributors: | 應數系 |
| Keywords: | 癌症;抗血管生成;節拍式治療
Cancer;Anti-angiogenesis;Metronomic therapy |
| Date: | 2021-10 |
| Issue Date: | 2025-04-16 14:28:24 (UTC+8) |
| Abstract: | 化療被廣泛運用於癌症的治療中。由於癌細胞在有絲分裂過程中會因基因突變產生抗藥性，因此傳統化療觀念是治療時施予患者所能忍受的最大藥物劑量，以求快速清除體內的癌細胞。然而, 受到藥物毒性限制，若施藥後無法完全清除體內的癌細胞，反覆施藥中必須引入停藥期供患者回復，而此期間癌細胞仍可能增生產生抗藥性，限制了治療的成效。1971年，腫瘤學家Folkman 提出抗血管生成的癌症療法，隨後在1990年代，醫藥界研發出血管內皮細胞生長因子抑制劑，可進行癌症抗血管生成治療。此類抑制劑因有免疫調節作用，且作用對象基因結構穩定被認為有不產生抗藥性的優點，廣受注目，也因此被用於長期低劑量治療癌症患者，稱為節拍式治療。在2000年，學者 Fidler 與 Ellis更提出癌症是一種慢性病，應視為慢性病治療, 亦即以藥物長期控制癌症。然而，不同於原先預期，證據顯示以血管生成抑制劑治療癌症時，仍會有抗藥性的問題。本計畫討論在抗藥性風險存在下，風險高低與藥物能將腫瘤控制在可容許範圍的時間長度之間關係，以探討長期採用血管生成抑制劑控制癌症的可行性，研究成果將有助於對節拍式治療的進一步瞭解及促進癌症治療方法發展。
Chemotherapy has been widely used in the treatment of cancer. Because mutation may occur when cancer cells undergo mitosis, which might lead to resistance, traditional chemotherapy applies maximum tolerated dose strategy to eliminate patients’ cancer cells as fast as possible. However, when cancer cells cannot be fully eliminated, repeated drug usage is necessary. Due to the constraint of toxicity, it is unavoidable to introduce rest periods between two usages of drugs for patients to recover. During these periods, the population of cancer cells grows and resistance problems might still occur. The occurrence of resistance greatly restricts the treatment efficacy and this motivates medical specialists to explore better treatment methods. In 1971, Judan Folkman proposed the concept of anti-angiogenesis therapy of cancer. Subsequently in 1990, vascular endothelial growth factor inhibitors were invented. This type of inhibitors has the benefit of immunity stimulation and is believed to be resistance free because they act on targets which are genetic stable. Henceforth, they are proposed to treat cancer in a long-term low-dose manner, called metronomic therapy. In 2000, Fidler and Ellis even claimed that “Cancer is a chronic disease and should be treated like other chronic disease.” That is, to treat cancer through long-term drug control.Contrary to expectation, clinic evidence shows that resistance problems may still occur in anti-angiogenesis therapy of cancer. This raises the concern of whether it is possible to use vascular growth inhibitors for the long-term control of cancer. This project investigates the relationship between the risk of drug resistance and the maximal duration of time that the disease progression of cancer can be well controlled. It seeks to explore the feasibility of controlling cancer progression as chronic diseases with anti-angiogenesis therapy. The results will lead to a better understanding to metronomic therapy and might assist the development of better treatment method of cancer. |
| Relation: | 科技部, MOST109-2221-E004-003, 109.08-110.07 |
| Data Type: | report |
| Appears in Collections: | [應用數學系] 國科會研究計畫
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