Journal of Medical Oncology and Therapeutics

TARGETING THE MULTIDRUG TRANSPORTER PATCHED POTENTIATES CHEMOTHERAPY EFFICIENCY IN VITRO AND IN VIVO

11^th International Conference on Cancer Stem Cells and Oncology Research
June 11-13, 2018 | Dublin, Ireland

Isabelle Mus-Veteau, Anida Hasanovic, Carmen Ruggiero, Sara Jung, Ida Rapa, Marco Volante, Constanze Hantel and Enzo Lalli

Institut de Pharmacologie Moleculaire et Cellulaire, France Ludwig-Maximilians-Universite, Germany University of Turin at San Luigi Hospital, Italy Universite Cote d Azur, France

Scientific Tracks Abstracts : J Med Oncl Ther

Abstract:

One of the crucial challenges in the clinical management of cancer is the resistance to chemotherapeutics. We recently demonstrated that the Hedgehog receptor Patched, which is overexpressed in many recurrent and metastatic cancers, is a multidrug transporter for chemotherapeutic agents such as doxorubicin. The present study provides evidences that Patched is expressed in adrenocortical carcinoma (ACC) patients, and is a major player of the doxorubicin efflux and the doxorubicin resistance in the human ACC cell line H295R. We discovered a drug-like molecule which inhibits the doxorubicin efflux activity of Patched, enhances the cytotoxic, pro-apoptotic, antiproliferative and anticlonogenic effects of doxorubicin on ACC cells which endogenously overexpress Patched, and thereby mitigates the resistance of these cancer cells to doxorubicin. Moreover, we report that in mice the combination of this molecule with doxorubicin prevents the development of xenografted ACC tumors more efficiently than doxorubicin alone by enhancing the accumulation of doxorubicin specifically in tumors without obvious undesirable side effect. Our results suggest that the use of an inhibitor of Patched drug efflux in combination with doxorubicin could be a promising therapeutic option for adrenocortical carcinoma, and most likely also for other Patched-expressing cancers.

Biography:

Isabelle Mus-Veteau is currently working at the Institut de Pharmacologie Moléculaire et Cellulaire, Sophia Antipolis, Université Côte d’Azur, France

Email:mus-veteau@ipmc.cnrs.fr

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