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Background: Ovary Carcinoma (OC) is the most lethal gynecological neoplasm due to the late diagnoses and to the common development of resistance to platinum-based chemotherapy. Thus, novel therapeutic approaches are urgently required. In this regard, the strategy of drug repurposing is becoming attractive. By this approach, the effectiveness of a drug originally developed for another indication is tested in a different pathology. The advantage is that data about pharmacokinetic properties and toxicity are already available. Thus, in principle, it is possible to reduce research costs and to speed up drug usage/marketing. Results: Here, some noticeable examples of repurposed drugs for OC, such as amiodarone, ruxolitinib, statins, disulfiram, ormeloxifenem, and Quinacrine, are reported. Amiodarone, an antiarrhythmic agent, has shown promising anti-OC activity, although the systemic toxicity should not be neglected. The JAK inhibitor, Ruxolitinib, may be employed particularly in coadministration with standard OC therapy as it synergistically interacts with platinum-based drugs. Particularly interesting is the use of statin which represent one of the most commonly administered drugs in aged population to treat hypercholesterolemia. Disulfiram, employed in the treatment of chronic alcoholism, has shown anti-OC properties. Ormeloxifene, commonly used for contraception, seems to be promising, especially due to the negligible side effects. Finally, Quinacrine used as an antimicrobial and anti-inflammatory drug, is able to downregulate OC cell growth and promote cell death. Conclusion: Whereas further testing in patients are necessary to better clarify the therapeutic potential of repurposed drugs for OC, it is believed that their use, better if combined with OC targeted delivery systems, can significantly contribute to the development of novel and effective anti-OC treatments.

The RNA interference (RNAi) is a biological process by which a double stranded RNA (dsRNA also called small interfering RNA - siRNA) triggers the sequence-dependent degradation of a target RNA within the cellular environment. Thus siRNAs can be used to combat the expression of deleterious gene(s) causing disease or to destroy invading pathogen RNAs. Despite their enormous therapeutic potential, the use of siRNA as drugs presents two major problems: the difficulties to identify optimal delivery systems and the possible induction of different unwanted side effects. In this review, after presenting an overview about the mechanisms ruling the process of RNAi, we focus the attention on the description of the strategies developed to optimise systemic siRNA delivery; in this sense, considerations about the attempts to improve siRNA stability in the biological environment, the development of synthetic vectors for siRNA delivery, the siRNA bio-distribution and pharmacokinetics together with the selection of siRNA targeted delivery systems, are discussed. Since in the optimisation of the siRNA delivery systems the minimization of siRNA side effects should not be neglected, in the last part of the review we consider the problems related to the possible induction of siRNA mediated side effects focusing on the so called microRNA like off-targeting.

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the third leading cause of cancer-related death. Because of the fast growth, early hepatic metastasis and the multidrug resistance, the five-year survival rate is very low. Thus, the understanding of its biology can significantly contribute in identifying valuable targets for novel therapeutic approaches. In this regard, E2F1 may represent an interesting candidate. E2F1 is a transcription factor implicated in the regulation of many cellular processes including cell proliferation and apoptosis. Whereas the involvement of E2F1 in HCC has been recognized, its ability to act as a proliferative and/or apoptotic factor in HCC has not yet been clarified and, in this regard, an active debate is ongoing. The definition of E2F1 role in HCC is not a trivial aspect as it can have significant consequences for the development of novel therapeutic options with E2F1 as target. In this review, we present data about the reported proliferative/apoptotic effects as well as the dual (combined proliferation and apoptosis) functions of E2F1 in HCC discussing the molecular basis for this behavior. The data available so far indicate that the proliferative and apoptotic functions of E2F1 in HCC may coexist but the proliferative effect seems to be more pronounced than the apoptotic one.