Telomere Length Regulation Unit, Children's Medical Research Institute, Faculty of Medicine and Health, University of Sydney, Westmead, NSW 2145, Australia.
Telomere Length Regulation Unit, Children's Medical Research Institute, Faculty of Medicine and Health, University of Sydney, Westmead, NSW 2145, Australia.
Curr Opin Genet Dev. 2020 Feb;60:25-30. doi: 10.1016/j.gde.2020.02.006. Epub 2020 Feb 28.
Telomere maintenance is essential for the continued proliferation of mitotically active cells. Alternative Lengthening of Telomeres (ALT) is a recombination-dependent pathway of telomere maintenance analogous to break-induced replication (BIR) [1] that becomes activated in approximately 10-15% of human cancers. ALT is prevalent in tumours of mesenchymal or neuroepithelial origin, and typically confers a poor prognosis. The aggressiveness and lack of effective strategies to treat these cancers make the ALT pathway a compelling potential therapeutic target to prevent tumour formation and/or the appearance of secondary malignancies after conventional chemotherapy [2]. While the precise initiator of ALT during tumourigenesis remains elusive, substantial progress has been made in interrogating the underlying homology-directed repair mechanisms that converge at telomeres to enable telomere length maintenance. Here, we describe recent advances in our understanding of the ALT mechanism and highlight potential therapeutic targets that may offer future promise in the treatment of ALT cancers.
端粒维持对于有丝分裂活性细胞的持续增殖至关重要。端粒的非经典延长（ALT）是一种依赖于重组的端粒维持途径，类似于断裂诱导复制（BIR）[1]，在大约 10-15%的人类癌症中被激活。ALT 在间充质或神经上皮来源的肿瘤中普遍存在，通常预示预后不良。这些癌症的侵袭性和缺乏有效的治疗策略使得 ALT 途径成为一个引人注目的潜在治疗靶点，以防止肿瘤形成和/或常规化疗后继发性恶性肿瘤的出现[2]。虽然 ALT 在肿瘤发生过程中的确切启动因素仍然难以捉摸，但在研究导致端粒维持的同源定向修复机制方面已经取得了实质性进展。在这里，我们描述了我们对 ALT 机制的理解的最新进展，并强调了可能为 ALT 癌症的治疗提供未来希望的潜在治疗靶点。
