Addressing the Challenge: Current and Future Directions in Ovarian Cancer Therapy

Abstract

Numerous ovarian gene therapy strategies are in clinical phases based on concepts of replacement/ knock out of deregulated gene, suicide gene strategies, strengthening of the immune response against a tumor, inhibition of tumor angiogenesis and growth factors. Non-viral delivery systems have potential advantages over currently widely used viral vectors and other classical vectors for delivering therapeutic gene of interest. The present review provides a comprehensive overview of potential of various delivery systems currently in use. Non-viral formulations used in ovarian gene therapy include injecting naked DNA, liposomes, polyplexes, lipopolyplexes, nanoparticles, gene gun and ultrasound/microbubble mediated gene delivery. In addition to improving vector delivery, the DNA constructs need to be optimised for both efficient and long-term transgene expression. Minicircles using minimal immunological defined gene expression (MIDGE) technology, are a promising future alternative to plasmid for use in non-viral ovarian gene therapy in terms of biosafety, improved gene transfer, potential bioavailability, minimal size and little immune reaction. The review explores the best route of administration for ovarian cancer gene therapy given its peritoneal dissemination which poses a major challenge in treating ovarian cancer patients. Enhancement of therapeutic index can be further achieved by overcoming barriers both at cellular and nuclear levels. Selective tumor targeting with minimal toxicity using folate modified, incorporating nuclear localization signal and PEGylated stealth liposome's represents a popular approach and needs to be exploited in ovarian gene therapy.

Optimizing Molecular-Targeted Therapies in Ovarian Cancer: The Renewed Surge of Interest in Ovarian Cancer Biomarkers and Cell Signaling Pathways

“…Ingenious approaches are currently being applied to precisely map signal transduction pathways and target key molecular role players that direct ovarian tumor sensitivity and resistance to therapy and OS rates in patients. These include improved ultrasound and imaging technologies, molecular genetic analysis, as well as genomic, transcriptomic, and proteomic profiling of novel ovarian tumor biomarkers [2, 7, 14, 16, 56, 61, 72, 76–94]. In view of the complexities and variable response rates experienced with ovarian cancer patients clinically, the aim of this review is to outline recent developments in our understanding of the interrelationships among selected ovarian tumor biomarkers, heterogeneous expression signatures and related molecular signal transduction pathways, and their translation into futuristic as well as more efficacious targeted treatment rationales.…”

Advances in Gene Delivery Systems

“…This method has been utilized in vaccination against the influenza virus [127] and in gene therapy for treatment of ovarian cancer. [128] …”

Perspectives in Nanomedicine-Based Research Towards Cancer Therapies

“…Kaur et al [38] reviewed the potential of various delivery systems for ovarian cancer particularly non-viral formulations used in ovarian gene therapy like injecting naked DNA, liposomes, polyplexes, lipopolyplexes, nanoparticles, gene gun and ultrasound/microbubble mediated gene delivery. This study explored the best route of administration for ovarian cancer gene therapy as given its peritoneal dissemination that poses a major challenge in treating ovarian cancer patients.…”