The Influences of Genomic Polymorphisms on Treatment Outcomes and Toxicity in Patients with Colorectal Carcinoma

基因體多型性對大腸直腸癌病患化學治療療效及毒性所產生的影響

王緯書(Wei-Shu Wang)

《台灣癌症醫學雜誌》 28卷1期 (2012/02) Pp. 3-17

https://doi.org/10.6323/JoCRP.2012.28.1.1

摘要

過去四十年來，5-Fluorouracil（5-FU）一直是轉移性大腸直腸癌病患化學治療最主要的藥物，也是該類病患接受手術後輔助性化學治療的主要藥物。於轉移性、手術無法切除的大腸直腸癌病患，單獨使用5-FU的反應率為百分之十到二十。此外，於第三期大腸直腸癌病患手術完全切除腫瘤後，使用5-FU作為輔助性化學治療，可以提升總存活率約百分之二十。若將5-FU與oxaliplatin 或irinotecan合併使用，或加上標靶藥物，可以有效提升治療的反應率至大約百分之五十。然而仍有約半數轉移性、手術無法切除的大腸直腸癌病患化學治療無效，其原因在於先天性或後天獲得性因素對化療或標靶藥物產生抗藥性。本文整理分析目前已被發現在治療轉移性大腸直腸癌病患時，會影響療效、預後及毒性的生物標記，特別是基因多型性方面的標記。希望藉由對這些生物標記的了解，有助於提升化學治療的療效並降低其毒性，達到量身訂做、客製化醫療的目標。

關鍵字

基因體多型性 ； 化學治療 ； 大腸直腸癌

並列摘要

For the last four decades, 5-fluorouracil (5-FU) has been the treatment of choice for colorectal cancer (CRC) in both the advanced and adjuvant settings. In the advanced setting, 5-FU monotherapy produces response rates of only 10% to 20%. Furthermore, in resected stage III CRC, 5-FU monotherapy has increased overall survival by only 20%. The combination of 5-FU with newer therapies such as oxaliplatin and irinotecan, and targeted drugs has significantly improved response rates to approximately 50%. Despite these improvements, approximately half of advanced CRC patients derive no benefit from treatment; this is due to either acquired or inherent drug resistance. This review aims to highlight the current prognostic and predictive markers, especially genomic polymorphisms, which have been identified for CRC to date. The use of these predictive markers might improve the response rates and decrease toxicity for CRC patients, with an ultimate aim to tailor treatment according to individual patient and tumor profile.

並列關鍵字

genomic polymorphisms ； chemotherapy ； colorectal carcinoma