Mottaghi-Dastjerdi Negar, Soltany-Rezaee-Rad Mohammad
Department of Pharmacognosy and Pharmaceutical Biotechnology, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran.
Behestan Innovation Factory, Behestan Darou, Tehran, Iran.
Iran J Pharm Res. 2025 May 25;24(1):e159954. doi: 10.5812/ijpr-159954. eCollection 2025 Jan-Dec.
Gastric cancer (GC) is a major global health burden, with drug resistance representing a critical barrier to effective treatment. Understanding the mechanisms underlying drug resistance and leveraging advanced technologies, such as artificial intelligence (AI), are essential for developing innovative therapeutic strategies.
This review systematically examines the primary mechanisms of drug resistance in GC, organized into eight categories: Reduced drug uptake, enhanced drug efflux, impaired pro-drug activation or increased inactivation, molecular target alterations, enhanced DNA damage repair, imbalance in apoptotic regulation, tumor microenvironment modifications, and phenotypic changes. Additionally, the role of AI in addressing these challenges is explored, with a focus on omics-driven insights, pathway analysis, biomarker discovery, and modeling drug-response relationships.
The review highlights the transformative potential of AI in advancing precision therapy for GC. Key applications include therapeutic stratification, optimization of drug combinations, adaptive therapy design, and integration with clinical workflows. Challenges such as data quality, model interpretability, and the need for interdisciplinary collaboration are identified, along with strategies to address these barriers. Future directions emphasize the development of explainable AI models, integration of multi-omics and real-time patient data, and AI-driven drug discovery targeting resistance pathways.
By bridging research and clinical practice, AI offers a promising path to more effective, personalized, and adaptive therapeutic strategies for GC. Overcoming existing challenges and leveraging AI's potential can significantly improve treatment outcomes and address the pressing issue of drug resistance in GC.
胃癌是全球主要的健康负担,耐药性是有效治疗的关键障碍。了解耐药性的潜在机制并利用人工智能(AI)等先进技术对于制定创新治疗策略至关重要。
本综述系统地研究了胃癌耐药的主要机制,分为八类:药物摄取减少、药物外排增强、前药激活受损或失活增加、分子靶点改变、DNA损伤修复增强、凋亡调控失衡、肿瘤微环境改变和表型变化。此外,还探讨了人工智能在应对这些挑战中的作用,重点是组学驱动的见解、通路分析、生物标志物发现以及药物反应关系建模。
该综述强调了人工智能在推进胃癌精准治疗方面的变革潜力。关键应用包括治疗分层、药物组合优化、适应性治疗设计以及与临床工作流程的整合。确定了数据质量、模型可解释性以及跨学科合作需求等挑战,以及应对这些障碍的策略。未来方向强调可解释人工智能模型的开发、多组学和实时患者数据的整合,以及针对耐药通路的人工智能驱动的药物发现。
通过架起研究与临床实践之间的桥梁,人工智能为胃癌提供了一条通往更有效、个性化和适应性治疗策略的有希望的途径。克服现有挑战并利用人工智能的潜力可以显著改善治疗结果,并解决胃癌中紧迫的耐药性问题。