The Role of Alternative Lengthening of Telomeres Mechanism in Cancer Cells and the Research Progress of Controllable Alternative Lengthening of Telomeres

The key to the unlimited proliferation of cancer cells lies in their ability to maintain telomere length, thereby evading the normal mechanisms of cellular senescence and death. Cancer cells mainly sustain or lengthen telomeres through telomerase activation and telomere elongation replacement mechanisms. The former is targeted at clinical trials of telomerase inhibitors (Imetelstat), which are currently ongoing. However, there are still many unsolved mysteries regarding the specific molecular mechanism of the Alternative Lengthening of Telomeres (ALT)pathway, which limits the development of anti-cancer drugs targeting this pathway. By reviewing relevant literature, this review will discuss the progress and new discoveries of this mechanism in recent years. The research conclusion indicates that although progress has been made in inhibiting key targets of the telomeric substitution elongation pathway (such as topoisomerase III) and developing molecular tools, and a quality control mechanism has been discovered for ALT cancer cells, the specific delivery and toxicity management of targeted drugs remain challenges in clinical translation.