Copyright © 2012, American Association for Cancer Research.
PM01183 , Actualmente Terminando ya la Fase II en Ovario ... Cáncer de Ovario Epitelial, Encontar una Nueva Terapia que Supere la Resistencia a los Platinos es una Prioridad .(Hospital Universitari de Bellvitge) ...
Aqui tenemos unos Resultados ( Mayo 2012 ) de Fases Anteriores en Cancer de Ovario de este Farmaco de Pharma Mar ( G. Zeltia ) publicadas esta semana en la Publicación : Clinical Cancer Research de la American Association for Cancer Research :
Lurbinectedin (PM01183), a New DNA Minor Groove Binder, Inhibits Growth of Orthotopic Primary Graft of Cisplatin-Resistant Epithelial Ovarian Cancer.
Source Pathology, Hospital Universitari de Bellvitge.
Vidal A, Munoz C, Guillen MJ, Moreto J, Sara P, Martinez-Iniesta M, Figueras A, Padulles L, Garcia-Rodriguez FJ, Berdiel-Acer M, Pujana MA, Salazar R, Gil-Martin M, Marti L, Ponce J, Mollevi DG, Capella G, Condom E, Vinals F, Huertas D, Cuevas C, Esteller M, Aviles P, Villanueva A.
Abstract
PURPOSE: Epithelial ovarian cancer (EOC) is the fifth leading cause of death in women diagnosed with gynecological malignancies. The low survival rate is due to its advanced-stage diagnosis and either intrinsic or acquired resistance to standard platinum-based chemotherapy. So, the development of effective innovative therapeutic strategies to overcome cisplatin resistance remains a high priority.
EXPERIMENTAL DESIGN: To investigate new treatments in in vivo models reproducing EOCs tumor growth, we generated a preclinical model of ovarian cancer after orthotopic implantation of a primary serous tumor in nude mice. Further, matched model of acquired cisplatin-resistant tumor version was successfully derived in mice. Effectiveness of lurbinectedin (PM01183) treatment, a novel marine-derived DNA minor groove covalent binder, was assessed in both preclinical models as a single and a combined-cisplatin agent.
RESULTS: Orthotopically perpetuated tumor grafts mimic the histopathological characteristics of primary patients' tumors and they also recapitulate in mice characteristic features of tumor response to cisplatin treatments. We demonstrated that single lurbinectedin or cisplatin combined therapies were effective in treating cisplatin-sensitive and cisplatin-resistant preclinical ovarian tumor models. Furthermore, the strongest in vivo synergistic effect was observed for combined treatments, especially in cisplatin-resistant tumors. Lurbinectedin tumor growth inhibition was associated with reduced proliferation, increased rate of aberrant mitosis and subsequent induced apoptosis.
CONCLUSIONS: Taken together, preclinical orthotopic ovarian tumor grafts are useful tools for drug development, providing hard evidence that lurbinectedin might be a useful therapy in the treatment of epithelial ovarian cancer by overcoming cisplatin resistance.
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