Mengistu Bemrew Admassu, Tsegaw Tirunesh, Demessie Yitayew, Getnet Kalkidan, Bitew Abebe Belete, Kinde Mebrie Zemene, Beirhun Asnakew Mulaw, Mebratu Atsede Solomon, Mekasha Yesuneh Tefera, Feleke Melaku Getahun, Fenta Melkie Dagnaw
Department of Biomedical Sciences, College of Veterinary Medicine and Animal Sciences, University of Gondar, Gondar, Ethiopia.
Department of Veterinary Epidemiology and Public Health, College of Veterinary Medicine and Animal Sciences, University of Gondar, Gondar, Ethiopia.
Cancer Cell Int. 2024 Dec 18;24(1):406. doi: 10.1186/s12935-024-03558-0.
Cancer remains a significant global challenge, and despite the numerous strategies developed to advance cancer therapy, an effective cure for metastatic cancer remains elusive. A major hurdle in treatment success is the ability of cancer cells, particularly cancer stem cells (CSCs), to resist therapy. These CSCs possess unique abilities, including self-renewal, differentiation, and repair, which drive tumor progression and chemotherapy resistance. The resilience of CSCs is linked to certain signaling pathways. Tumors with pathway-dependent CSCs often develop genetic resistance, whereas those with pathway-independent CSCs undergo epigenetic changes that affect gene regulation. CSCs can evade cytotoxic drugs, radiation, and apoptosis by increasing drug efflux transporter activity and activating survival mechanisms. Future research should prioritize the identification of new biomarkers and signaling molecules to better understand drug resistance. The use of cutting-edge approaches, such as bioinformatics, genomics, proteomics, and nanotechnology, offers potential solutions to this challenge. Key strategies include developing targeted therapies, employing nanocarriers for precise drug delivery, and focusing on CSC-targeted pathways such as the Wnt, Notch, and Hedgehog pathways. Additionally, investigating multitarget inhibitors, immunotherapy, and nanodrug delivery systems is critical for overcoming drug resistance in cancer cells.
癌症仍然是一项重大的全球挑战，尽管已制定了众多推进癌症治疗的策略，但转移性癌症的有效治愈方法仍难以捉摸。治疗成功的一个主要障碍是癌细胞，特别是癌症干细胞（CSC）抵抗治疗的能力。这些癌症干细胞具有独特的能力，包括自我更新、分化和修复，这些能力推动肿瘤进展和化疗耐药性。癌症干细胞的韧性与某些信号通路有关。具有依赖通路的癌症干细胞的肿瘤通常会产生基因耐药性，而具有不依赖通路的癌症干细胞的肿瘤则会发生影响基因调控的表观遗传变化。癌症干细胞可以通过增加药物外排转运蛋白活性和激活生存机制来逃避细胞毒性药物、辐射和细胞凋亡。未来的研究应优先确定新的生物标志物和信号分子，以更好地理解耐药性。使用生物信息学、基因组学、蛋白质组学和纳米技术等前沿方法为这一挑战提供了潜在的解决方案。关键策略包括开发靶向疗法、采用纳米载体进行精确药物递送，以及关注针对癌症干细胞的信号通路，如Wnt、Notch和Hedgehog通路。此外，研究多靶点抑制剂、免疫疗法和纳米药物递送系统对于克服癌细胞的耐药性至关重要。
