Therapeutic Opportunities for Alternative Lengthening of Telomeres (ALT) Cancers

Cancers that rely on activation of the alternative lengthening of telomeres (ALT) pathway predominantly affect children and adolescents, and are associated with catastrophic outcomes due to a lack of clinically effective, targeted therapeutics. The exponential rise in our understanding of the ALT mechanism in recent years has led to the identification of many therapeutic targets and strategies for patients suffering from these cancers. These include targeting replication fork remodelers and DNA damage response pathways to exacerbate telomere-specific replication stress, inhibiting ALT-mediated telomere synthesis to induce telomere dysfunction, and using oncolytic viruses to selectively kill ALT cancer cells. Herein we will evaluate the advantages and shortfalls of these therapeutic strategies, and discuss current diagnostic opportunities that are a necessary accompaniment to direct ALT therapeutics to patients.