Biswas Siddhant, Kanodia Riya, Seervi Suman, Kaur Rajinder, Shukla Sakshi, Singh Samer, Banerjee Juni, Banerjee Shuvomoy
School of Biotechnology and Bioengineering, Institute of Advanced Research (IAR), Koba, Institutional Area, Gandhinagar, Gujarat, 382426, India.
Centre of Experimental Medicine & Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India.
Exp Cell Res. 2025 Jun 1;449(1):114580. doi: 10.1016/j.yexcr.2025.114580. Epub 2025 Apr 29.
Gastric cancer (GC) is an aggressive malignancy among all Gastrointestinal cancer (GIC) types. Worldwide, among all cancer types, gastric cancer incidence and related mortality remain in fifth position. Multidrug resistance (MDR) in GC presents a major challenge to chemotherapy, and it significantly affects patient survival. A better understanding of the dynamic interaction of cellular factors contributing to MDR phenotype, e.g., the presence and expression of variants of MDR-related genes, including various drug-detoxifying and drug-efflux transporters, and expression of regulatory ncRNAs affecting the expression of MDR-related genes, is required to comprehend the molecular mechanisms for MDR development in GCs. This review article provides a holistic discussion of the cellular factors involved in the MDR development in GC cells, i.e., their roles and cross-talk between specific molecules that give rise to drug-sensitive and drug-resistant phenotypes. Moreover, the pharmacological perspective of drug resistance and the underlying biological processes that allow the escape of GC cells from the cytotoxic effects of drugs have also been discussed. Additionally, this review article provides an in-depth discussion on most potential candidates that can serve as MDR biomarkers in GIC cancer and the growing research interest in non-coding RNAs (ncRNAs) in GC. Notably, the miRNAs, circRNAs, and lncRNAs are not only emerging as crucial prognostic biomarkers of MDR in gastric cancers but also as potential targets for personalized medicine to combat the MDR challenge in GC patients.
胃癌（GC）是所有胃肠道癌症（GIC）类型中侵袭性很强的恶性肿瘤。在全球范围内，在所有癌症类型中，胃癌的发病率和相关死亡率仍位居第五。胃癌中的多药耐药性（MDR）对化疗构成了重大挑战，并显著影响患者的生存率。为了理解胃癌中MDR发生发展的分子机制，需要更好地了解促成MDR表型的细胞因子之间的动态相互作用，例如MDR相关基因变体的存在和表达，包括各种药物解毒和药物外排转运蛋白，以及影响MDR相关基因表达的调控性非编码RNA（ncRNA）的表达。这篇综述文章全面讨论了参与胃癌细胞MDR发生发展的细胞因子，即它们在产生药物敏感和耐药表型的特定分子之间的作用和相互作用。此外，还讨论了耐药性的药理学观点以及使胃癌细胞逃避药物细胞毒性作用的潜在生物学过程。此外，这篇综述文章深入讨论了最有可能作为GIC癌症中MDR生物标志物的候选物，以及对胃癌中非编码RNA（ncRNA）日益增长的研究兴趣。值得注意的是，微小RNA（miRNA）、环状RNA（circRNA）和长链非编码RNA（lncRNA）不仅正成为胃癌中MDR的关键预后生物标志物，而且还作为个性化医学的潜在靶点，以应对胃癌患者的MDR挑战。
