Liu Xiangdong, Zhang Wanqiu, Wei Shaozhong, Liang Xinjun, Luo Bo
Department of Radiotherapy Center, Hubei Cancer Hospital, The Seventh Clinical School Affiliated of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Hubei Provincial Clinical Research Center for Colorectal Cancer, Wuhan, China.
Front Pharmacol. 2024 Dec 3;15:1451067. doi: 10.3389/fphar.2024.1451067. eCollection 2024.
Colorectal cancer has emerged as one of the predominant malignant tumors globally. Immunotherapy, as a novel therapeutic methodology, has opened up new possibilities for colorectal cancer patients. However, its actual clinical efficacy requires further enhancement. Copper, as an exceptionally crucial trace element, can influence various signaling pathways, gene expression, and biological metabolic processes in cells, thus playing a critical role in the pathogenesis of colorectal cancer. Recent studies have revealed that cuproptosis, a novel mode of cell death, holds promise to become a potential target to overcome resistance to colorectal cancer immunotherapy. This shows substantial potential in the combination treatment of colorectal cancer. Conveying copper into tumor cells via a nano-drug delivery system to induce cuproptosis of colorectal cancer cells could offer a potential strategy for eliminating drug-resistant colorectal cancer cells and vastly improving the efficacy of immunotherapy while ultimately destroy colorectal tumors. Moreover, combining the cuproptosis induction strategy with other anti-tumor approaches such as photothermal therapy, photodynamic therapy, and chemodynamic therapy could further enhance its therapeutic effect. This review aims to illuminate the practical significance of cuproptosis and cuproptosis-inducing nano-drugs in colorectal cancer immunotherapy, and scrutinize the current challenges and limitations of this methodology, thereby providing innovative thoughts and references for the advancement of cuproptosis-based colorectal cancer immunotherapy strategies.
结直肠癌已成为全球主要的恶性肿瘤之一。免疫疗法作为一种新型治疗方法，为结直肠癌患者开辟了新的可能性。然而，其实际临床疗效仍需进一步提高。铜作为一种极其重要的微量元素，可影响细胞内的各种信号通路、基因表达和生物代谢过程，因此在结直肠癌的发病机制中起着关键作用。最近的研究表明，铜死亡作为一种新的细胞死亡模式，有望成为克服结直肠癌免疫治疗耐药性的潜在靶点。这在结直肠癌的联合治疗中显示出巨大潜力。通过纳米药物递送系统将铜输送到肿瘤细胞中以诱导结直肠癌细胞发生铜死亡，可能为消除耐药性结直肠癌细胞、大幅提高免疫治疗疗效并最终摧毁结直肠肿瘤提供一种潜在策略。此外，将诱导铜死亡的策略与光热疗法、光动力疗法和化学动力疗法等其他抗肿瘤方法相结合，可进一步增强其治疗效果。本综述旨在阐明铜死亡及诱导铜死亡的纳米药物在结直肠癌免疫治疗中的实际意义，并审视该方法当前面临的挑战和局限性，从而为基于铜死亡的结直肠癌免疫治疗策略的推进提供创新思路和参考。
