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MicroRNAs sensitize ovarian cancers to platinum chemotherapy

技術優勢

- MicroRNAs miR-520-a, g, and/or h dramatically sensitize ovarian cancers to platinum-based chemotherapy. Thus, synthetic mimics for miR-520h can be used to increase the potency of platinum-based agents, while reducing the incidence of side effects and dramatically improving outcomes.- The present invention is useful and effective for treating a wide range of other cancers, given the central role that platinum-based agents play in standard of care treatment for other human cancers,- The compositions of the invention are unique in that they target multiple gene products across different signaling pathways involved in platinum resistance.- The reagents used to synthesize these liposomes can allow for the cost effective, readily scalable mass production of a clinical vector that can be incorporated into standard of care treatments for ovarian cancer.

詳細技術說明

None

*Abstract

Ovarian cancer is the 5th leading cause of cancer death for women in the United States. Although advances in surgery and chemotherapy have improved 5-year survival to nearly 50%, most (~80%) women with ovarian cancer eventually die from their disease. Platinum-based chemotherapy is the standard of care for all women newly diagnosed with ovarian cancer. However, approximately 20% of women with advanced ovarian cancers demonstrate de novo resistance to these agents. Additionally, recurrent ovarian cancer eventually becomes resistant to platinum-based therapy. Ultimately, nearly all (>90%) of women with ovarian cancer die from a platinum-resistant recurrence of their disease. Although higher doses of platinum agents have been shown to induce better responses, their use is limited because of the toxicity associated with dose escalation.Recent evidence has implicated a family of small RNA transcripts known as microRNAs in ovarian cancer. The inventors identified specific microRNAs that sensitize human cancers to cytotoxic chemotherapy, including miR-520a/g/h. Moreover, they have shown that using mimics for at least one of these microRNAs (miR-520h, for example) can dramatically sensitize established ovarian cancer cell lines to cisplatin. Most dramatically, the representative miR-520h improves survival of mice xenografted with ovarian cancer when treated with less than 5% of the dose of cisplatin currently used to clinically manage ovarian cancer in women.

國家/地區

美國