Funding (ICMUB):
Duration: Oct. 22 – 48 months
Scientific leader ICMUB: David Monchaud
Summary
High-grade osteosarcomas (OS) are highly aggressive malignant bone tumors that mainly occur in children and adolescents. Their therapeutic management includes neoadjuvant chemotherapy, which in pediatric contexts consists of the combination of high-dose methotrexate, ifosfamide and VP16, followed by surgery, and then adjuvant chemotherapy. When metastatic, the 5-year survival rate of these tumors is less than 30 %, indicating the critical need for new treatment strategies. This proposal is about uncovering a new target to devise an innovative therapeutic strategy: all human cancers need to maintain and protect their chromosome ends. The vast majority of cancers (>80%) upregulate telomerase, while a minor fraction of them (<20%) rely on a mechanism called alternative lengthening of telomeres (ALT) based on homologous recombination (HR)-mediated DNA replication. OS exhibit a high frequency of ALT activation; to investigate this further, we analyzed in this project the telomere maintenance mechanism in a cohort of 22 non-metastatic, non-pre-treated and high-grade OS, which led us to formulate a novel hypothesis for the OS oncogenetic process, that is, to identify a novel target for therapeutic intervention.
Partners:
- Vincent Géli, CRCM Marseille, FR
- Anne Gomez, IUCT Toulouse, FR
- Corinne Bouvier, APHM Marseille, FR
- Etienne Coyaud, PRISM Lille, FR
- Natascha Entz-Werle, CHU Strasbourg, FR