Fatima Narjis, Crassini Kyle R, Thurgood Lauren, Shen Yandong, Christopherson Richard I, Kuss Bryone, Mulligan Stephen P, Best Oliver Giles
Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, Sydney, NSW 2065, Australia.
School of Life and Environmental Sciences, University of Sydney, Sydney NSW 2008, Australia.
Cancer Drug Resist. 2020 May 11;3(3):532-549. doi: 10.20517/cdr.2019.111. eCollection 2020.
The treatment of chronic lymphocytic leukaemia has been revolutionised in recent years, first by the introduction of chemoimmunotherapy regimens and subsequently by the development of drugs, including ibrutinib, idelalisib and venetoclax, that target components of the B-cell receptor signalling pathway or B-cell lymphoma 2 family of proteins. Despite high initial response rates in patients treated with chemoimmunotherapy or targeted agents, a significant proportion of patients relapse with progressive and refractory disease. In a subset of these patients, drug resistance has been associated with specific genetic lesions or activation of alternate pro-survival pathways. However, the mechanisms that confer drug resistance in the remainder of the patients with refractory disease have yet to be fully elucidated. In this review, we discuss our current understanding of the mechanics of drug resistance in chronic lymphocytic leukaemia and describe how this knowledge may aid in rationalising future treatment strategies to prevent the development of refractory or aggressive transformation of the disease.
近年来，慢性淋巴细胞白血病的治疗发生了革命性变化，首先是引入了化疗免疫治疗方案，随后是开发了包括伊布替尼、艾代拉里斯和维奈托克在内的药物，这些药物靶向B细胞受体信号通路的组成部分或B细胞淋巴瘤2蛋白家族。尽管接受化疗免疫治疗或靶向药物治疗的患者初始缓解率较高，但仍有相当一部分患者会出现疾病进展和难治性复发。在这些患者的一个亚组中，耐药性与特定的基因损伤或替代生存促进途径的激活有关。然而，在其余难治性疾病患者中导致耐药的机制尚未完全阐明。在这篇综述中，我们讨论了目前对慢性淋巴细胞白血病耐药机制的理解，并描述了这些知识如何有助于合理制定未来的治疗策略，以防止疾病发展为难治性或侵袭性转变。
Zotero 插件