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.