Targeting epithelial-mesenchymal transition and cancer stem cells for chemoresistant ovarian cancer

Abstract

Chemoresistance is the main challenge for the recurrent ovarian cancer therapy and responsible for treatment failure and unfavorable clinical outcome. Understanding mechanisms of chemoresistance in ovarian cancer would help to predict disease progression, develop new therapies and personalize systemic therapy. In the last decade, accumulating evidence demonstrates that epithelial-mesenchymal transition and cancer stem cells play important roles in ovarian cancer chemoresistance and metastasis. Treatment of epithelial-mesenchymal transition and cancer stem cells holds promise for improving current ovarian cancer therapies and prolonging the survival of recurrent ovarian cancer patients in the future. In this review, we focus on the role of epithelial-mesenchymal transition and cancer stem cells in ovarian cancer chemoresistance and explore the therapeutic implications for developing epithelial-mesenchymal transition and cancer stem cells associated therapies for future ovarian cancer treatment.

Epithelial-mesenchymal transition and inflammation at the site of the primary tumor

“…The association of EMT with poor clinical outcome also supports the concept that mesenchymalization (i.e. the acquisition of mesenchymal features) renders cancer cells resistant to the cytotoxic effect of anti-cancer therapeutics, including chemotherapy [86, 87] radiation [88], small-molecule targeted therapies [89, 90] and, as recently demonstrated, lysis by immune effector cells [91, 92]. …”

Neutralization of IL-8 decreases tumor PMN-MDSCs and reduces mesenchymalization of claudin-low triple-negative breast cancer

“…Mesenchymalization and the molecular drivers of the process, including the transcription factors Snail, Slug, Twist, and brachyury, have been linked to advanced tumor stage (36)(37)(38), presence of metastases (39), and poor prognosis in numerous cancer types (40)(41)(42). Additionally, mesenchymalization has been associated with resistance to anticancer therapies, including chemotherapy (43,44), small-molecule-targeted therapies (45,46), and to lysis by immune effector cells (47)(48)(49)(50). In the case of breast cancer, this phenomenon has been linked to tumor progression in preclinical models (51) and with patient tumor samples (52,53).…”

The evolving concept of cancer stem-like cells in thyroid cancer and other solid tumors

“…It appears that a small population of cells in cancer that is capable of self-renewal is responsible for tumor initiation, growth and recurrence in a variety of cancers. [5][6][7][8][9][10][11][12] Numerous biomarkers to characterize CSCs have been reported. However, the specificity of many of these markers in terms of their ability to differentiate CSCs vs other cancer cells has not been completely demonstrated [7][8][9][10][11] (Table 1).…”

“…4,5,12,18,23,25,28,31,36,37,39,40,[108][109][110] Figure 1 Diagrammatic illustration of epithelial to mesenchymal transition (EMT) and interaction of cancer stem cells (CSCs) with the tumor microenvironment. EMT is influenced by multiple factors and TGFβ-induced EMT is a useful experimental model.…”