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.

中文翻译：

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在人类癌症中驱动端粒维持和重组的机制。

端粒的维持对于有丝分裂活性细胞的持续增殖至关重要。端粒的替代性延长（ALT）是端粒维持的重组依赖性途径，类似于断裂诱导的复制（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起源的肿瘤中普遍存在，通常预后不良。侵袭性和缺乏有效的治疗这些癌症的策略使得ALT通路成为预防常规化疗后预防肿瘤形成和/或继发性恶性肿瘤出现的引人注目的潜在治疗靶点[2]。尽管在肿瘤生成过程中ALT的确切引发剂仍然难以捉摸，在研究潜在的由同源性指导的修复机制方面取得了实质性进展，修复机制在端粒处汇聚以实现端粒长度的维持。在这里，我们描述了我们对ALT机制的理解方面的最新进展，并重点介绍了可能为ALT癌症的治疗提供未来希望的潜在治疗靶标。