Inhibition of Patched Chemotherapy Resistance Activity: biocomputational, chemical and cellular approaches
Sandra Kovachka
Doctoral Candidate in 3rd year
Abstract
Cancer drug resistance is a major problem of chemotherapy nowadays. Our team recently identified the Hedgehog receptor Patched as a drug efflux pump that participates to the resistance of cancer cells to chemotherapy. Thanks to a screening program, Panicein A hydroquinone (PAH), a natural compound purified from a marine sponge, was identified as an inhibitor of drug efflux activity of Patched. The synthesis of PAH allowed us to confirm that PAH increases the cytotoxic effect of several chemotherapeutic agents on melanoma cell lines in vitro and in vivo. The use of PAH in combination with chemotherapy may be a novel and innovative way to circumvent drug resistance, recurrence and metastasis of tumors.
The final objective is to obtain a clinical candidate that could be considered for clinical testing with a Pharma partner.
Supervisors
- Stéphane Azoulay, MCU HDR University of Nice, ICN CNRS UMR7272 Nice
- Isabelle Mus-Veteau, DR, IPMC, CNRS UMR7275 Sophia Antipolis
- Tutor from Academia
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Madalena Chaves, DR, INRIA, Sophia Antipolis
- Mentor from Industry
- Charles Henry Fabritius, Head Medicinal Chemistry, TOLREMO therapeutics AG, Basel, Switzerland
International 6-months secondment in Italy
in the supervision of Paolo Ruggerone, Full Professor, Department of Physics, University of Cagliari