Plasticity in Ovarian Cancer: The Molecular Underpinnings and Phenotypic Heterogeneity

Abstract

Cellular plasticity, by large, is the ability through which cells morph into new phenotypic identity by trading-off with the previous one. This phenomenon has been observed in the normal and tumor cells in a very similar fashion. Occurrence of cellular plasticity, in malignancies like epithelial ovarian carcinoma (EOC) are well known but highly debated in terms of origin of the tumor for the inherent heterogeneity across subtypes. EOC has been termed as a clinically challenging malady for its subversive nature against chemotherapy. The management of ovarian cancer is mostly hindered by relapse with recalcitrance towards primary chemotherapy regimen e.g. platinum–taxol combination. Also, late detection preceded by peritoneal metastasis poses another challenge to the treatment. Underlying both these aspects of the disease, tumor heterogeneity turns out as the most critical factor. In the light of heterogeneity that can be across patients (inter-tumoral) and/or within a tumor (intra-tumoral), ovarian carcinoma is a multifactorial ailment. The governing factors behind this heterogeneity are—diverse genetic landscape among subtypes of EOC; the presence of cancer stem cell (CSC) niche and inherent plasticity of the cancer cells themselves. Apart from the well-studied mechanisms of plasticity, there are several emerging molecular players like lncRNAs, Hippo pathway and also phenomena like dedifferentiation of non-CSC neoplastic cells ,and transdifferentiation of CSCs. Here, we present an overview of the current knowledge on the evolution of EOC through cellular plasticity with emphasis on the three major aspects namely, subtype-specific genetic diversity; ovarian CSC and cancer cell duality between epithelial and mesenchymal lineages.