Abstract
The main challenge in ovarian cancer treatment is the management of recurrences. Facing this scenario, therapy selection is based on multiple factors to define the best treatment sequence. Target therapies, such as bevacizumab and polymerase (PARP) inhibitors, improved patient survival. However, despite their achievements, ovarian cancer survival remains poor; these therapeutic options are highly costly and can be associated with potential side effects. Recently, it has been shown that the combination of repurposed, conventional, chemotherapeutic drugs could be an alternative, presenting good patient outcomes with few side effects and low costs for healthcare institutions. The main aim of this review is to strengthen the importance of repurposed drugs as therapeutic alternatives, and to propose an in vitro model to assess the therapeutic value. Herein, we compiled the current knowledge on the most promising non-oncological drugs for ovarian cancer treatment, focusing on statins, metformin, bisphosphonates, ivermectin, itraconazole, and ritonavir. We discuss the primary drug use, anticancer mechanisms, and applicability in ovarian cancer. Finally, we propose the use of these therapies to perform drug efficacy tests in ovarian cancer ex vivo cultures. This personalized testing approach could be crucial to validate the existing evidences supporting the use of repurposed drugs for ovarian cancer treatment.
Highlights
Ovarian cancer (OC) is the leading cause of gynaecological cancer-related mortality worldwide [1,2]
Ivermectin, a polycyclic lactone pesticide produced by Streptomyces avermitilis bacterium, is a broad-spectrum antiparasitic agent [152] that binds with high affinity to the glutamic acid operative chloride ion channel localized in nerve and muscle cells in invertebrates [153,154]
A recent in vitro and in vivo study demonstrated that ivermectin induce cytostatic autophagy in breast cancer cells linked to the inhibition of PAK-1 expression leading to a reduced phosphorylation of Akt and blockage of Akt/mammalian target of rapamycin (mTOR) signalling pathway inhibiting tumour growth [163,168]
Summary
Ovarian cancer (OC) is the leading cause of gynaecological cancer-related mortality worldwide [1,2]. We propose an alternative approach based on the use of non-oncological drugs for OC treatment This concept, called drug repurposing, is based on the knowledge of pharmacokinetics, pharmacodynamics, target identification, bioavailability, toxicity profiles, recommended dosage schemes, and consistent recognition of adverse effects, meaning that oncological indication development can begin at phase II of the clinical trials, making the research process less time-consuming and less expensive [17,18,19,20]. In the OC setting, many non-oncological drugs have promising in vitro results and some of them already being tested in clinical trials. These therapeutic compounds include antifungal (itraconazole), antilipidemic (statins), antidiabetic (metformin), antiviral (ritonavir), antiparasitary (ivermectin) drugs, and osteoporosis treatment (bisphosphonates). We gather information about the most promising drug repurposing strategies for OC treatment and propose a strategy to test these therapeutic options in patient-derived samples
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