Publication date: Jul 07, 2025
A key hallmark of cancer tumorigenesis is the maintenance of telomere length, which occurs canonically through the reactivation of telomerase. Alternative lengthening of telomeres (ALT) is an atypical, non-canonical telomere maintenance mechanism that uses homologous recombination (HR) to maintain telomere length and is associated with replication stress and defects in genome maintenance. In preclinical models, ALT positivity (ALT+) sensitizes tumor cells to ataxia telangiectasia and Rad3-related (ATR) inhibitors. Camonsertib is a novel potent, and highly selective ATR inhibitor that is synthetic lethal with genomic alterations affecting HR and DNA damage response (DDR). Here we describe a case of confirmed clinical and molecular response to pharmacological ATR inhibition through camonsertib, in a patient with ALT+ metastatic melanoma. To our knowledge, this is the first clinical report of synthetic lethal targeting of a confirmed ALT+ tumor with an ATR inhibitor.
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Semantics
| Type | Source | Name |
|---|---|---|
| disease | MESH | melanoma |
| pathway | KEGG | Melanoma |
| disease | MESH | cancer |
| disease | MESH | tumorigenesis |
| pathway | REACTOME | Telomere Maintenance |
| pathway | KEGG | Homologous recombination |
| disease | MESH | defects |
| disease | MESH | ataxia telangiectasia |
| drug | DRUGBANK | Honey |
| drug | DRUGBANK | Nivolumab |
| drug | DRUGBANK | Ipilimumab |
| drug | DRUGBANK | Olaparib |
| drug | DRUGBANK | Trametinib |
| pathway | REACTOME | Methylation |
| drug | DRUGBANK | Coenzyme M |
| disease | MESH | metastasis |
| disease | MESH | anemia |
| disease | MESH | leukemia |
| disease | MESH | noma |
| drug | DRUGBANK | Formaldehyde |
| drug | DRUGBANK | Methionine |
| drug | DRUGBANK | Ethanol |
| drug | DRUGBANK | Sodium Chloride |
| drug | DRUGBANK | Edetic Acid |
| drug | DRUGBANK | Phosphate ion |
| drug | DRUGBANK | Medical air |
| drug | DRUGBANK | Sodium Citrate |
| drug | DRUGBANK | Tromethamine |
| drug | DRUGBANK | Gold |
| drug | DRUGBANK | Water |
| disease | MESH | microsatellite instability |
| disease | MESH | acinar carcinoma |
| pathway | REACTOME | Reproduction |