Overcoming Clear Cell Ovarian Cancer Resistance to Taxol by an Oligo Arginine Transporter Conjugate

Abstract

Objectives: Taxol remains first line treatment for all epithelial ovarian cancer (EOC). However, it has been shown that ovarian clear cell carcinoma (CCC), a rare histological subtype of EOC, often becomes resistant to platinum based therapy when at advanced stage. This chemo-resistant phenotype has led to a poorer prognosis in patients with CCC than in patients with serous subtypes. While many factors contribute to resistance; a major contributor is the active export of drugs from cells mediated by transmembrane efflux pumps that prevent drugs from reaching their intracellular targets. Our lab has developed a Taxol-oligoarginine conjugate that prevents export of the drug from serous papillary EOC leading to increased cell death. In this study we aim to assess whether this Taxol conjugate is effective in improving Taxol mediated cell death in platinum resistant Clear cell ovarian cancer.