Abstract
Ovarian cancer is the most lethal neoplasm of the female genital organs. Despite indisputable progress in the treatment of ovarian cancer, the problems of chemo-resistance and recurrent disease are the main obstacles for successful therapy. One of the main reasons for this is the presence of a specific cell population of cancer stem cells. The aim of this review is to show the most contemporary knowledge concerning the biology of ovarian cancer stem cells (OCSCs) and their impact on chemo-resistance and prognosis in ovarian cancer patients, as well as to present the treatment options targeted exclusively on the OCSCs. The review presents data concerning the role of cancer stem cells in general and then concentrates on OCSCs. The surface and intracellular OCSCs markers and their meaning both for cancer biology and clinical prognosis, signaling pathways specifically activated in OCSCs, the genetic and epigenetic regulation of OCSCs function including the recent studies on the non-coding RNA regulation, cooperation between OCSCs and the tumor microenvironment (ovarian cancer niche) including very specific environment such as ascites fluid, the role of shear stress, autophagy and metabolic changes for the function of OCSCs, and finally mechanisms of OCSCs escape from immune surveillance, are described and discussed extensively. The possibilities of anti-OCSCs therapy both in experimental settings and in clinical trials are presented, including the recent II phase clinical trials and immunotherapy. OCSCs are a unique population of cancer cells showing a great plasticity, self-renewal potential and resistance against anti-cancer treatment. They are responsible for the progression and recurrence of the tumor. Several completed and ongoing clinical trials have tested different anti-OCSCs drugs which, however, have shown unsatisfactory efficacy in most cases. We propose a novel approach to ovarian cancer diagnosis and therapy.
Highlights
Ovarian cancer (OC) is the most lethal tumor of the female genital tract due to aggressive behavior, late diagnosis and high recurrence potential
Compared to the efficacy of treatment that has been obtained during the last decade in breast cancer, which was considered another female “killer tumor”, there is still great work to do in ovarian cancer patients
The populations of ovarian cancer stem cells (OCSCs) may differ in the same patient or among different patients depending on the cancer histologic type, advancement of the disease, patient health status and treatment regime
Summary
Ovarian cancer (OC) is the most lethal tumor of the female genital tract due to aggressive behavior, late diagnosis and high recurrence potential. Ovarian cancer is a heterogeneous disease which comprise malignant tumors of serous, mucinous, endometrial or clear cell histology. Recent gene profiling studies allowed for a proposal of a new classification based on both gene expression pattern and histological structure. According to this classification ovarian cancer could be divided into five subtypes: mesenchymal, immunoreactive, proliferative, differentiated and anti-mesenchymal. Mesenchymal subtype show desmoplasia and mesenchymal gene expression pattern, proliferative subtype show limited inflammatory infiltration and activation of signaling pathways for stemness. Recent studies suggest that a unique population of tumor cells called cancer stem cells (CSCs) are the most probable reason for cancer progression and therapy failure in OC
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