Diagnosis and treatment of ALT tumors: is Trabectedin a new therapeutic option?

摘要: Telomeres are specialized nucleoprotein structures responsible for protecting chromosome ends in order to prevent the loss of genomic information. Telomere maintenance is required achieving immortality by neoplastic cells. While most cancer cells rely on telomerase re-activation linear and sustained proliferation, a significant population cancers (10–15%) employs telomerase-independent strategies, collectively referred as Alternative Lengthening (ALT). ALT mechanisms involve different types homology-directed telomere recombination synthesis. These processes facilitated ATRX or DAXX chromatin-remodeling factors abnormalities architecture. Although functional consequences up-regulation similar that they both overall shortening tumors, these (TMMs) differ several aspects which may account their differential prognostic significance response therapy various tumor types. Therefore, reliable methods detecting activity likely become an important pre-requisite use treatments targeting one other mechanisms. However, question whether presence can confer sensitivity rationally designed anti-cancer therapies still open. Here we review latest discoveries terms activation human identification cell lines tissues biomarkers validation. Then, original results rational based pre-clinical clinical anti-tumor drugs vs hTERT positive will be presented.