New strategies for the treatment of ovarian cancer

Abstract

Ovarian cancer usually responds well to chemotherapy, but once the disease becomes resistant to chemotherapy, the treatment options available are inadequate. A number of strategies are currently undergoing clinical evaluation, among which angiogenesis and PARP [poly(ADP-ribose) polymerase] inhibitors appear promising. Pre-clinical studies have identified several potential new therapeutic strategies, and we review the potential for use of BH3 (Bcl-2 homology) mimetics, autotaxin inhibitors and statins to treat ovarian cancer.

Statin as a Combined Therapy for Advanced-Stage Ovarian Cancer: A Propensity Score Matched Analysis

“…However, many patients experience recurrence and chemotherapy resistance, even though they response well initially. Consequently, the overall 5-year survival rate is about 40% after diagnosis with advanced-stage ovarian cancer [3]. Thus, effective and accessible adjuvant interventions for advanced-stage ovarian cancer are required.…”

“…On the other hand, emerging evidences supported the involvement of elevated cholesterol in reprogramming of metabolic program which augments the process of tumor development [6]. It has been suggested that statins inhibit cancer development through their inhibition of the mevalonate pathway, which could modify several proteins which is particularly necessary for the function of cancer cells, such as GTPases Ras, Rho, and Rab [3]. …”

“…However, the effect of statins in the clinical setting for the management of ovarian cancer patients remains unknown [3, 7]. Few studies reported the effect of statin therapy on ovarian cancer survival.…”

“…However, in a recent study that enrolled 442 ovarian cancer patients, improved survival among statin users was not demonstrated except in nonserous papillary epithelial ovarian cancer [10]. Furthermore, in some cancer cell lines, combining statin with carboplatin or paclitaxel revealed antagonistic effects, whereas the combination of taxane and platinum is a standard recommendation for ovarian cancer [3, 11]. …”

ABT‑737 and pictilisib synergistically enhance pitavastatin‑induced apoptosis in ovarian cancer cells

“…The activity of ABT-737 has previously been attributed to inhibition of the pro-apoptotic mediators, Bcl-2, Bcl-x L or Bcl-w, of which Bcl-x L is overexpressed in ovarian cancer (8,25). Statins have been shown to induce apoptosis through a number of pathways, including suppression of Akt/Erk activation (11,12), increased phosphorylation of the p38 MAPK pathway (12), and attenuation of Mcl-1, probably through the inhibition of NF-κB (26).…”