A Theoretical View of Ovarian Cancer Relapse

Abstract

Ovarian cancer (OC) is a disease that almost invariably relapses even after optimal primary cytoreductive surgery and standard first-line platinum-based chemotherapy. After recurrence, progressions occur at shorter intervals in the natural history of the disease. However, the biologic and cellular events underlying recurrence and progression (maintenance phase) are yet to be completely understood. Ovarian adenocarcinoma, like any other tissue, after reduction of the cell population (cytoreduction) either by surgery, chemotherapy, radiotherapy, or targeted therapies induced cell-death, tends to its own renewal through cancer stem cells (CSC). CSC remain quiescent most of their lives and then ‘wake up’, generating a proliferative progeny that differentiates as they become different clones of daughter cells. What defines them is their ‘self-renewal’ potential, thus perpetuating the disease with higher tumour volume relapses in which CSC increase in number. We propose a theory of how recurrence/relapse occurs in which CSC play a key role in the genesis of relapse. These self-renewing CSC can generate a proliferative progeny and this population is sensitive to chemotherapy, anti-angiogenic agents, and PARP inhibitors, which so far have only increased the disease/relapse free survival (‘maintenance phase’). In OC it seems we are not addressing the ‘root’ of recurrence/relapse. As with any theory, this is based on both proven facts and suggested hypotheses, which may serve as investigation drivers towards finally making a substantial improvement in OC management.