Anish Ruban S, Raj Francis Jegan, Thangaraj Parimelazhagan
Bioprospecting Laboratory, Department of Botany, Bharathiar University, Coimbatore 641046, Tamil Nadu, India.
Bioprospecting Laboratory, Department of Botany, Bharathiar University, Coimbatore 641046, Tamil Nadu, India.
Biochim Biophys Acta Rev Cancer. 2025 Jul;1880(3):189349. doi: 10.1016/j.bbcan.2025.189349. Epub 2025 May 6.
Drug resistance (DR) remains a significant challenge in cancer treatment, accounting for over 90 % of cancer-related deaths. Multidrug resistance (MDR) complicates chemotherapy by enabling cancer cells to evade therapeutic agents. This review focuses on the role of ATP-binding cassette (ABC) transporters, particularly the breast cancer resistance protein (BCRP), in mediating drug resistance. BCRP functions as a drug efflux pump, actively transporting chemotherapeutic agents out of cancer cells, thereby reducing their efficacy. The regulation of BCRP is influenced by various signaling pathways, including PI3K/AKT, MAPK/ERK, NF-κB, and Wnt/β-catenin, all of which collectively enhance its expression and contribute to the MDR phenotype. Recent studies have highlighted the potential of phytochemical-based strategies to reverse drug resistance by inhibiting these transporters. Compounds such as tetrandrine and resveratrol have shown promise in sensitizing drug-resistant cancer cells. Understanding the complex interplay between BCRP regulation and these signaling pathways is essential for the development of effective therapeutic strategies to counteract cancer. Targeting multiple pathways or employing combination therapies may offer new avenues to overcome MDR and improve treatment outcomes for cancer patients.
耐药性(DR)仍然是癌症治疗中的一个重大挑战,占癌症相关死亡人数的90%以上。多药耐药性(MDR)使癌细胞能够逃避治疗药物,从而使化疗变得复杂。本综述重点关注ATP结合盒(ABC)转运蛋白,特别是乳腺癌耐药蛋白(BCRP)在介导耐药性中的作用。BCRP作为一种药物外排泵,将化疗药物主动转运出癌细胞,从而降低其疗效。BCRP的调节受多种信号通路影响,包括PI3K/AKT、MAPK/ERK、NF-κB和Wnt/β-连环蛋白,所有这些信号通路共同增强其表达并导致MDR表型。最近的研究强调了基于植物化学物质的策略通过抑制这些转运蛋白来逆转耐药性的潜力。粉防己碱和白藜芦醇等化合物在使耐药癌细胞敏感化方面显示出前景。了解BCRP调节与这些信号通路之间的复杂相互作用对于开发对抗癌症的有效治疗策略至关重要。靶向多种途径或采用联合疗法可能为克服MDR和改善癌症患者的治疗结果提供新途径。