Qureshi Zaheer, Altaf Faryal, Safi Adnan, Khanzada Mikail, Ghazanfar Ali, Shah Shivendra
The Frank H. Netter M.D. School of Medicine at Quinnipiac University, Bridgeport, Connecticut, USA.
Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/BronxCare Health System, New York, USA.
Ann Med Surg (Lond). 2024 Nov 12;86(12):7290-7298. doi: 10.1097/MS9.0000000000002730. eCollection 2024 Dec.
In this review, the complicated landscape of breast cancer management is explored with a focus on the promising synergies between ribociclib and endocrine therapy. Ribociclib mainly acts as a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, which disrupts cell cycle progression necessary for tumor growth. This, in combination with endocrine therapy, aims to produce hormone receptor-positive breast cancers, which is a very relevant subtype with challenging therapeutics.
A comprehensive review was conducted using multiple databases, PubMed, Embase, Scopus, Cochrane Library, and Web of Science, covering the period from January 1990 to May 2024.
Pharmacokinetic studies underscore the efficacy and tolerability of ribociclib, thus providing vital information for dose adjustments, particularly among patients with renal and hepatic impairments. Ribociclib's value in extending progression-free survival and improving overall survival has been shown by clinical trials such as the MONALEESA series. Quality of life considerations and patient-reported outcomes from these trials indicate that ribociclib has a broader effect on the well-being of the patients. However, despite the success experienced by this drug in clinical practice, it still has some side effects, including hematologic toxicity, hepatotoxicity, and thromboembolism associated with it. Ribociclib resistance mechanisms are multifaceted mixtures comprising genetic variations or mutations, compensatory signaling pathways, and epigenomic changes. While overcoming resistance remains challenging, ongoing research seeks to reconcile.
Ribociclib combined with endocrine therapy represents a significant advancement in breast cancer treatment, albeit with challenges that necessitate ongoing research and holistic patient care approaches.
在本综述中,探讨了乳腺癌治疗的复杂格局,重点关注瑞博西尼与内分泌治疗之间有前景的协同作用。瑞博西尼主要作为一种细胞周期蛋白依赖性激酶4/6(CDK4/6)抑制剂发挥作用,它会破坏肿瘤生长所需的细胞周期进程。这与内分泌治疗相结合,旨在治疗激素受体阳性乳腺癌,这是一种治疗颇具挑战性的重要亚型。
使用多个数据库进行了全面综述,这些数据库包括PubMed、Embase、Scopus、Cochrane图书馆和Web of Science,涵盖1990年1月至2024年5月期间。
药代动力学研究强调了瑞博西尼的疗效和耐受性,从而为剂量调整提供了重要信息,特别是在肾和肝功能受损的患者中。瑞博西尼在延长无进展生存期和提高总生存期方面的价值已在如MONALEESA系列等临床试验中得到证实。这些试验中对生活质量的考量以及患者报告的结果表明,瑞博西尼对患者的幸福感有更广泛的影响。然而,尽管这种药物在临床实践中取得了成功,但它仍有一些副作用,包括血液学毒性、肝毒性以及与之相关的血栓栓塞。瑞博西尼耐药机制是多方面的组合,包括基因变异或突变、代偿性信号通路和表观基因组变化。虽然克服耐药性仍然具有挑战性,但正在进行的研究力求解决这一问题。
瑞博西尼与内分泌治疗相结合代表了乳腺癌治疗的重大进展,尽管存在挑战,需要持续研究和全面的患者护理方法。