Cisplatin Resistance in Ovarian Cancer: Classical Outlook and Newer Perspectives

Abstract

Ovarian cancer is one of the most common gynecological cancers. Recently, there is increase in incidence of ovarian cancer not only India but also worldwide. Ovarian cancer patients exhibit nonspecific symptoms during early course of disease. As a consequence, 70% of these patients are diagnosed in advanced stages. Ovarian cancer treatment includes cytoreductive surgery followed by platinum-based chemotherapy. However, these patients develop fatal recurrence due to development of platinum resistance. Cisplatin, (platinum analog) resistance is multifactorial and complex. Earlier, resistance was mainly attributed to conventional molecular mechanisms like decreased intracellular accumulation of cisplatin, enhanced DNA repair and increased cisplatin detoxification. Nevertheless, emergence of knowledge of tumor biology have lead to discovery of other contributing mechanisms. These tumor microenvironment related factors include physical blockade, hypoxia, cancer stem cells, cancer associated fibroblasts and many others. Understanding these mechanisms of cisplatin resistance is crucial for development of novel strategy to combat the same. Hence, this review summarizes all the mechanisms of resistance of cisplatin in ovarian cancer.