結直腸癌（CRC）是全球常見且致死率極高的癌症之一。因此，本論文整理及分析去氧核醣核酸(DNA) 修復機制在CRC抗藥性中的所扮演的角色。首先介紹CRC在臨床上的兩大分期系統於預測病情和制定治療計畫十分重要，Dukes分期系統是依腫瘤侵犯深度和有無轉移分成A至D期，而TNM分期系統是根據腫瘤的大小與範圍、淋巴結轉移的情況及遠端的轉移來分階段。接著論述目前CRC主要的五種療法，分別是手術、放射線治療、化學治療、標靶治療和免疫治療。其中，放射治療是誘導DNA損傷以消滅腫瘤細胞，而化療藥物如5-Fluorouracil, Oxaliplatin等是破壞DNA的功能，免疫治療藥物如Pembrolizumab, Nivolumab等是增強病人的免疫系統去對抗錯配修復缺陷或高微衛星不穩定性的大腸癌，標靶治療藥物如Cetuximab, Bevacizumab則是抑制與腫瘤生長因子相關的路徑。雖然這些療法改善了患者的症狀，但是因為CRC細胞內DNA修復能力的增強，而使得病人產生抗性。然而CRC在治療過程中所產生的抗性可能與幾條主要的DNA修復途徑相關，這些途徑包括鹼基切除修復（OGG1/APE1 訊息傳導途徑）、核苷酸切除修復（ERCC1/XPA訊息傳導途徑）、錯配修復（MutS/EXO1訊息傳導途徑）、同源重組（MRN/BRCA訊息傳導途徑）以及非同源末端連接（DNA-PKcs/XRCC4訊息傳導途徑）。不過本評論性論文未提供原創性的實驗數據，而且未涉及其他導致抗性的因素如表觀遺傳調控、免疫反應及腫瘤微環境等論述。總結而言，透過回顧並整合過去研究的發現，本論文闡述DNA修復路徑如何與CRC治療過程中所產生抗性的相關性，以作為未來標靶治療的重要參考依據。

Colorectal cancer (CRC) is one of the most seen and deadly diseases globally. This thesis reviewed the role of deoxyribonucleic acid (DNA) repair mechanism in CRC drug resistance. First, the staging system for CRC such as the Dukes staging system and TNM staging system were introduced due to the essential role in CRC prognosis and treatment planning. The Dukes system stages the CRC by A to D and the TNM system stages the CRC by tumor size and invasion (T), lymph node involvement (N), and metastasis (M). Second, the current options for CRC treatments have a lot of approaches, including surgical intervention, radiation therapy, chemotherapy, targeted treatments, and immunotherapy. In particular, radiotherapy induces DNA damage to eliminate tumor cells and chemotherapeutical drugs such as 5-Fluorouracil and Oxaliplatin disrupt DNA function. In addition, immunotherapeutic drugs such as Pembrolizumab and Nivolumab enhance immune responses in tumors with mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H), and targeted therapeutical drugs such as Cetuximab and Bevacizumab inhibit tumor-promoting pathways. Although these therapies improve patient outcomes, resistance remains a huge challenge due to the enhanced DNA repair ability in CRC cells. The drug resistance of CRC treatment is associated with certain major DNA repair pathways, including base excision repair (OGG1/APE1 signaling pathway), nucleotide excision repair (ERCC1/XPA signaling pathway), mismatch repair (MutS/EXO1 signaling pathway), homologous recombination (MRN/BRCA signaling pathway) and non-homologous end joining (DNA-PKcs/XRCC4 signaling pathway). However, this literature-based review excluded the presentations of novel experimental data, and the description about epigenetic regulation, immune response, or tumor microenvironment. In conclusions, by reviewing and synthesizing findings from past studies, this thesis provided a clearer understanding of how DNA repair mechanisms contribute to therapeutic resistance in CRC, highlighted their relevance as potential therapeutic targets, and supported future efforts toward more effective and individualized treatment strategies for CRC.

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