TAS-102联合血管生成抑制剂治疗转移性胃癌的作用机制与研究进展

轩 峥岩, 骆玉 霜*
青海大学

摘要


近年来，TAS-102（曲氟尿苷替匹嘧啶）联合血管生成抑制剂在转移性胃癌（mGC）治疗中的协同效应逐渐成为研究热点。本文系统综述了其双重作用机制及临床研究进展。从机制层面，TAS-102通过抑制胸苷磷酸化酶（TP）阻断肿瘤细胞DNA合成与修复；而血管生成抑制剂（如阿帕替尼、贝伐珠单抗等）通过靶向VEGF/VEGFR信号通路调控血管通透性，二者联用可显著增强药物在肿瘤组织中的富集。临床研究显示，TAS-102联合血管生成抑制剂方案可获得显著生存获益。值得注意的是，基于循环肿瘤DNA（ctDNA）的动态监测提示，TP蛋白表达与VEGF信号通路基因变异可能成为疗效预测标志物。未来需进一步开展多中心Ⅲ期试验验证长期获益，并探索基于分子分型的精准联用策略。

关键词


曲氟尿苷替匹嘧啶（TAS-102）；血管生成抑制剂；晚期胃癌；联合治疗

全文:

PDF


参考


[1]F B, M L, H S, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J/OL]. CA: a cancer journal for clinicians, 2024, 74(3)[2025-03-30]. https://pubmed.ncbi.nlm.nih.gov/38572751/. DOI:10.3322/caac.21834.

[2]Sun Xiao,et al. ESMO Asia Virtual Congress 2020.e-Poster.150P.[M].

[3]2024晚期胃癌诊疗指南更...SCO、NCCN和ESMO_蓝煜[Z].

[4]YULE M S, BROWN L R, WALLER R, et al. Cancer cachexia[J/OL]. BMJ, 2024, 387[2024-12-12]. https://www.bmj.com/content/387/bmj-2024-080040. DOI:10.1136/bmj-2024-080040.

[5]曲氟尿苷替匹嘧啶在消化道肿瘤中的研究进展_邹佳运[Z].

[6]XU J, KIM T W, SHEN L, et al. Results of a Randomized, Double-Blind, Placebo-Controlled, Phase III Trial of Trifluridine/Tipiracil (TAS-102) Monotherapy in Asian Patients With Previously Treated Metastatic Colorectal Cancer: The TERRA Study[J/OL]. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 2018, 36(4): 350-358. DOI:10.1200/JCO.2017.74.3245.

[7]SHITARA K, DOI T, DVORKIN M, et al. Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomised, double-blind, placebo-controlled, phase 3 trial[J/OL]. The Lancet Oncology, 2018, 19(11): 1437-1448. DOI:10.1016/S1470-2045(18)30739-3.

[8]OKUNAKA M, KAWAZOE A, NAKAMURA H, et al. Efficacy and safety of trifluridine/tipiracil plus ramucirumab in comparison with trifluridine/tipiracil monotherapy for patients with advanced gastric cancer-single institutional experience[J/OL]. Gastric Cancer: Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2023, 26(6): 1030-1039. DOI:10.1007/s10120-023-01427-9.

[9]BAEKSGAARD JENSEN L, YILMAZ M, NORDSMARK M, et al. TRIFLURIDINE/TIPIRACIL (FTD/TPI) with or without bevacizumab in previously treated patients with esophago-gastric adenocarcinoma, a randomised phase III trial[J/OL]. eClinicalMedicine, 2024, 70: 102521. DOI:10.1016/j.eclinm.2024.102521.

[10]ZHANG Q, XIANG W, YI D Y, et al. Current status and potential challenges of mesenchymal stem cell-based therapy for malignant gliomas[J/OL]. Stem Cell Research & Therapy, 2018, 9(1): 228. DOI:10.1186/s13287-018-0977-z.

[11]KAWAZOE A, ANDO T, HOSAKA H, et al. Safety and activity of trifluridine/tipiracil and ramucirumab in previously treated advanced gastric cancer: an open-label, single-arm, phase 2 trial[J/OL]. The Lancet. Gastroenterology & Hepatology, 2021, 6(3): 209-217. DOI:10.1016/S2468-1253(20)30396-4.

[12]ANDRÉ T, FALCONE A, SHPARYK Y, et al. Trifluridine-tipiracil plus bevacizumab versus capecitabine plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer ineligible for intensive therapy (SOLSTICE): a randomised, open-label phase 3 study[J/OL]. The Lancet. Gastroenterology & Hepatology, 2023, 8(2): 133-144. DOI:10.1016/S2468-1253(22)00334-X.

[13]抗血管生成酪氨酸激酶抑制剂在实体瘤中的临床研究进展_徐蕊[Z].

[14]WILKE H, VAN CUTSEM E, OH S C, et al. RAINBOW: A global, phase III, randomized, double-blind study of ramucirumab plus paclitaxel versus placebo plus paclitaxel in the treatment of metastatic gastroesophageal junction (GEJ) and gastric adenocarcinoma following disease progression on first-line platinum- and fluoropyrimidine-containing combination therapy rainbow IMCL CP12-0922 (I4T-IE-JVBE).[J/OL]. Journal of Clinical Oncology, 2014, 32(3_suppl): LBA7-LBA7. DOI:10.1200/jco.2014.32.3_suppl.lba7.

[15]WANG F, SHEN L, GUO W, et al. Fruquintinib plus paclitaxel versus placebo plus paclitaxel for gastric or gastroesophageal junction adenocarcinoma: the randomized phase 3 FRUTIGA trial[J/OL]. Nature Medicine, 2024, 30(8): 2189-2198. DOI:10.1038/s41591-024-02989-6.

[16]ZHANG Y, XU J, WANG Q, et al. Efficacy and safety of second-line therapy with apatinib combined with chemotherapy as second-line therapy in advanced gastric cancer: a single-arm, open-label, prospective, multicenter study[J/OL]. Annals of Translational Medicine, 2022, 10(11): 641-641. DOI:10.21037/atm-22-2752.

[17]CHEN Z, HUANG W, TIAN T, et al. Characterization and validation of potential therapeutic targets based on the molecular signature of patient-derived xenografts in gastric cancer[J/OL]. Journal of Hematology & Oncology, 2018, 11(1): 20. DOI:10.1186/s13045-018-0563-y.

[18]瑞戈非尼联合每两周一次TAS-102治疗难治性转移性结直肠癌（REGTAS）的疗效和安全性：一项多中心单臂II期试验。|临床肿瘤学杂志[EB/OL].[2025-03-31]. https：//ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.e15567.

[19]消化系统恶性肿瘤应用抗血管...引起不良反应及中药规律探讨_张嫄爽[Z].

[20]ZHAO B, ZHAO H, ZHAO J. Incidence and Risk of Fatal Adverse Events in Cancer Patients Treated With Vascular Endothelial Growth Factor Receptor 2-Targeted Agents: A Meta-Analysis With Trial Sequential Analysis of Randomized Controlled Trials[J/OL]. Frontiers in Medicine, 2019, 6: 176. DOI:10.3389/fmed.2019.00176.

[21]KUANG H, YAN Q, LI Z, et al. Comprehensive analysis of VEGF/VEGFR inhibitor-induced immune-mediated hypertension: integrating pharmacovigilance, clinical data, and preclinical models[J/OL]. Frontiers in Immunology, 2024, 15: 1488853. DOI:10.3389/fimmu.2024.1488853.

[22]PD-1_PD-L1抑制剂...免疫治疗晚期肝癌的研究进展_黄燕妮（1）[Z].

[23]HO H Y, CHUNG K S K, KAN C M, et al. Liquid Biopsy in the Clinical Management of Cancers[J/OL]. International Journal of Molecular Sciences, 2024, 25(16): 8594. DOI:10.3390/ijms25168594.


Refbacks

  • 当前没有refback。