Monoamine oxidase inhibitors and methods for treatment and diagnosis of prostate cancer

Abstract

A mechanism of monoamine oxidases (MAOs) driven epithelium-to-mesenchymal transition (EMT) is disclosed. Also disclosed are methods for treating cancer by inhibiting or suppressing MAOs in cancer cells. Novel MAOs inhibitors, such as small molecules, siRNA, shRNA, antisense oligonucleotides, aptamers, decoys, and pharmaceutical compositions useful for treating cancer by disrupting the workings of MAOs are provided. In particular, a class of conjugates formed by covalently conjugating near infrared dye 783, IR-780, and MHI-148 to a MAO inhibitor, such as clorgyline, with and without encapsulation it in a nanoparticle is provided. Other aspects of the invention include methods for forming the nano-conjugates, method for monitoring treatment progress in a cancer patient by monitoring the changes in MAO activity, methods for screening patients who are at risk of cancer or differentiating different forms of cancer by assaying the level and location of MAO activity.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation of U.S. application Ser. No. 13 / 559,431 (now U.S. Pat. No. 9,771,625; issued Sep. 26, 2017) filed on Jul. 26, 2012, which claims the benefit of priority of U.S. Provisional Application No. 61 / 511,920 filed Jul. 26, 2011, all of which are incorporated herein by reference in their entirety.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH AND DEVELOPMENT[0002]This invention was made with government support under Contract Nos. P01-CA98912, DAMD-17-03-02-0033, R01-CA122602, R01-MH39085 awarded by the National Institute of Health. The government has certain rights in the invention.FIELD OF THE INVENTION[0003]The present invention relates generally to inhibition of monoamine oxidases (MAOs) and their inhibitors (MAOIs) as strategies to treat cancer, particularly prostate cancer. This invention also relates to imaging, screening, diagnostics, and therapeutic methods of cancer. In addition, this invention further...

AI Technical Summary

Benefits of technology

The present invention is about using nanoparticles that are taken up by cancer cells to deliver pharmaceutical agents to treat the cancer. The nanoparticles are designed to be preferential to cancer cells and can carry a therapeutic compound. The invention also includes a method to monitor the progress of treatment using a near-infrared dye based nano-conjugate and imaging technology. The imaging can be done non-invasively and in real-time using a Xenogen IVIS system. The invention has potential to improve the effectiveness of treating cancer and minimize the damage to healthy cells.

Problems solved by technology

However, they are only effective for patients during the early stages of the disease.

There are also undesired side effects associated with each of these treatment modalities.

Moreover, for patients with advanced stages of castration-resistant and metastatic prostate cancers, these treatments are only partially effective.

Despite the improvement, these additional therapies, in general, are only capable of prolonged survival by a few months.

However, the Gleason system is entirely reliant upon human visual examination, which is prone to error with significant limitations on early detection.

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