Wang QingShui, Xue Fangqin, Assaraf Yehuda G, Lin Yao
Affiliated People's Hospital, Fujian-Macao Science and Technology Cooperation Base of Traditional Chinese Medicine-Oriented Chronic Disease Prevention and Treatment, Fujian-Hong Kong-Macau-Taiwan Collaborative Laboratory for the Inheritance and Innovation of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, Fujian, China.
Department of Gastrointestinal Surgery, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, 350001, China.
Int J Biol Sci. 2025 Jul 11;21(10):4604-4628. doi: 10.7150/ijbs.113709. eCollection 2025.
Gastric cancer remains a major cause of mortality. The current standard of care of gastric cancer is based upon combination chemotherapy comprising platinum, fluoropyrimidines drugs and docetaxel. However, the efficacy of chemotherapy is hindered by intrinsic and acquired drug resistance, resulting in poor patient prognosis. Studies are currently exploring the potential of immunotherapy and other biologically targeted agents in the perioperative setting. To select the most efficacious therapy for advanced gastric cancer, including adenocarcinoma of the esophago-gastric junction, it is essential to determine key biomarkers including for example human epidermal growth factor receptor 2 (HER2) expression, programmed death-ligand 1 (PD-L1) combined positive score (CPS), Claudin 18.2, and microsatellite instability (MSI). Moreover, recent studies have highlighted the potential of natural products as effective agents in surmounting anticancer drug resistance in gastric cancer. These bioactive compounds exhibit various antitumor activities, including induction of apoptosis, inhibition of cell proliferation, modulation of autophagy, and most importantly reversal of distinct multidrug resistance (MDR) modalities. The present review provides a comprehensive analysis of the mechanisms underlying chemoresistance in gastric cancer and explores how natural products can overcome distinct MDR mechanisms. We further discuss the therapeutic potential of combining natural products with established chemotherapeutics and immunotherapy agents to enhance treatment efficacy and reduce adverse effects.
胃癌仍然是主要的死亡原因。目前胃癌的标准治疗方案是基于铂类、氟嘧啶类药物和多西他赛的联合化疗。然而，化疗的疗效受到内在和获得性耐药的阻碍，导致患者预后不良。目前的研究正在探索免疫疗法和其他生物靶向药物在围手术期的潜力。为了为晚期胃癌（包括食管胃交界腺癌）选择最有效的治疗方法，确定关键生物标志物至关重要，例如人表皮生长因子受体2（HER2）表达、程序性死亡配体1（PD-L1）联合阳性评分（CPS）、Claudin 18.2和微卫星不稳定性（MSI）。此外，最近的研究强调了天然产物作为克服胃癌抗癌耐药性的有效药物的潜力。这些生物活性化合物具有多种抗肿瘤活性，包括诱导凋亡、抑制细胞增殖、调节自噬，最重要的是逆转不同的多药耐药（MDR）模式。本综述对胃癌化疗耐药的潜在机制进行了全面分析，并探讨了天然产物如何克服不同的MDR机制。我们进一步讨论了将天然产物与既定的化疗药物和免疫治疗药物联合使用以提高治疗效果并减少不良反应的治疗潜力。
