Benzoquinone derivative E3330 in combination with chemotherapeutic agents for the treatment of cancer and angiogenesis

Abstract

Disclosed are novel methods for the therapeutic treatment of cancer and angiogenesis. The enzyme Apel / Ref-1, via its redox function, enhances the DNA binding activity of transcription factors that are associated with the progression of cancer. The present invention describes the use of agents to selectively inhibit the redox function of Apel / Ref-1 and thereby reduce tumor cell growth, survival, migration and metastasis. In addition, Apel / Ref-1 inhibitory activity is shown to augment the therapeutic effects of other therapeutics and protect normal cells against toxicity. Further, Apel / Ref-1 inhibition is shown to decrease angiogenesis, for use in the treatment of cancer as well other pathologic conditions of which altered angiogenesis is a component.

Description

[0001] This application is an invention patent application named "Benzoquinone derivative E3330 combined with chemotherapeutic agent for the treatment of cancer and angiogenesis" with the application number 200880117660.0 filed on September 22, 2008 and the priority date being November 21, 2007 divisional application. [0002] Cross References to Related Applications [0003] This application claims priority to U.S. Provisional Patent Application No. 60 / 989,566, filed November 21, 2007, and U.S. Provisional Patent Application No. 60 / 975,396, filed September 26, 2007, the entire contents of which are hereby incorporated by reference . technical field [0004] The present invention relates generally to the fields of molecular biology, biochemistry and pathology. More specifically, in some aspects, the present invention relates to the application of Ape1 / Ref-1 redox inhibitors in cancer treatment and angiogenesis inhibition. Background technique [0005] Apurinic / apyrimidini...

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Problems solved by technology

High expression of Ape1 / Ref-1 is associated with poor effect of radiotherapy and chemotherapy, low complete response rate, short local recurrence-free interval, poor survival and more angiogenesis (Koukourakis et al., Int J Radiat Oncol Biol Phys 2001,50, 27; Kakolyris et al., Br J Cancer 1998, 77, 1169; Bobola et al., Clin Cancer Res 2001, 7, 3510).

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