Beca publicada por el Ministerio italiano de educación, Universidad e investigación 21/06/2015 .
Advanced bone and soft tissue sarcomas (BSTS) still represent an unmet medical need due to their chemoresistance. The DNA repair machinery is crucial in overcoming chemotherapy-induced DNA damage. Trabectedin induces a DNA damage that leads to PARP-1 activation, therefore PARP-1 inhibitor olaparib was shown to increase trabectedin activity in preclinical models of BSTS. Our division is conducting a phase I trial with the combination of trabectedin and olaparib in advanced BSTS (TOMAS trial, NCT02398058 ). To identify determinants of response/resistance to trabectedin and olaparib combination in patients enrolled in TOMAS trial. The winner of the research grant will be involved in: -phase I trial conduction -evaluation of preliminary evidences of activity in order to select the most/less responsive BSTS histotypes to trabectedin and olaparib wherein to explore the metabolic pathways involved with the aim to identify candidate biomarkers of response.
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