How to win the ovarian cancer stem cell battle: destroying the roots

Abstract

Ovarian cancer has the highest mortality rate among gynecologic malignancies. The combination of cytoreductive surgery and chemotherapy is the standard regimen for the treatment of ovarian cancer. The initial treatment is usually effective, but many patients with ovarian cancer experience recurrence, and treatment options for recurrent disease remain challenging. Cancer stem cells (CSCs) are suggested to play an essential role in cancer recurrence after initial chemotherapy. Furthermore, they are of great interest as CSCs may also be involved in chemotherapy susceptibility. Thus, understanding the characteristics and mechanisms by which CSCs display resistance to therapeutic agents is important to design effective cancer treatments. In this review, we describe and discuss current therapeutic regimens for ovarian cancer, as well as the various CSC markers, association between CSCs and disease progression, correlation of CSCs with poor prognosis, enrichment of CSCs in tumor tissues following repeated chemotherapy cycles, activation of major signaling pathways following chemotherapy, and potential inhibitors that suppress these signaling cascades. In addition, clinical trials evaluating novel targeted therapies to overcome chemotherapy resistance will be reviewed. The combination of traditional chemotherapy and CSCtargeted therapy could be an effective and promising anticancer treatment for ovarian cancer. Understanding the biological properties of CSCs and the mechanism of chemotherapy resistance are critical to design and develop new therapeutic strategies to overcome CSC-associated chemotherapy resistance.

The MEK1/2 Pathway as a Therapeutic Target in High-Grade Serous Ovarian Carcinoma

“…At the cellular level, analysis of cisplatin-sensitive vs. cisplatin-resistant tumors revealed that resistant cells descend from pre-existing minor subpopulations in the primary tumor [16], which most likely represent cancer stem-like cells (CSCs) [17][18][19][20][21][22][23]. CSCs possess high resistance to cytotoxic and genotoxic effects, are capable of self-renewal, and asymmetric division that generates a progeny of fast-proliferating bulk tumor cells [24]. CSCs possess a high tumorigenic potential and can re-initiate tumor development after chemotherapeutic treatment [18,25,26].…”

Cancer Stem Cell Markers—Clinical Relevance and Prognostic Value in High-Grade Serous Ovarian Cancer (HGSOC) Based on The Cancer Genome Atlas Analysis

“…The cancer cell populations derived from a single patient are highly diverse [ 2 , 3 ]. Cancer stem cells (CSCs), the subpopulation of neoplastic cancer cells able to self-renew [ 4 , 5 ], contribute to chemotherapy resistance [ 2 , 5 , 6 , 7 ]. CSCs have been detected in OC tumors in the early and advanced stages before and after the conventional treatment [ 8 , 9 , 10 ].…”

Role of RAS signaling in ovarian cancer

“… 188 , 189 Few CSC markers, including ALDH1, CD44, CD117, and CD133 are considered to be useful predictive or prognostic biomarkers of OC. 190 The platinum-based chemotherapy resistance and tumor cell stemness is associated with the recurrence in HGSOC. In an aggressive murine model of OC, the stem phenotypes with a gain of KRAS , MYC , and FAK genes were found to be associated with intrinsic platinum resistance and tumorsphere formation.…”