Tumor-mesenchymal stem cell interactions: therapeutic implications for epithelial ovarian cancer

Epithelial ovarian cancer (EOC) is the most common cause of gynecological cancer-related death (1). When compared to most solid tumors, EOC has a distinct mechanism of dissemination. Cells detach from the primary tumor and aggregate in peritoneal fluid to form free-floating multicellular spheroids, which then travel through the peritoneal fluid at distant sites onto the mesothelial lining where metastatic outgrowth occurs (2). Because this process is clinically silent, most women (~70%) present with metastasis throughout the peritoneal cavity. The current standard of care for EOC is debulking surgery combined with platinum-based chemotherapy (3). Drug resistance is one of the major obstacles in the treatment of EOC. EOC resistance can arise within tumor cells as a consequence of genetic changes leading to either intrinsic or acquired resistance (4). In addition, soluble factors and stromal cells within the tumor environment, which can promote the inhibition of drug-induced apoptosis, may constitute another mechanism of drug resistance (4). Despite optimal tumor-debulking surgery and initial high responses rates to first-line chemotherapy, most patients with advanced EOC relapse within 18–22 months with a disease that is still sensitive to the first-line therapy suggesting that their state of chemoresistance was transient and not associated with genetic changes in tumor cells in contrast to acquired or intrinsic resistance. This transient drug resistance state is thought to be driven by the surrounding tumor environment in EOC