Inos-inhibitory compositions and their use as breast cancer therapeutics

Abstract

Disclosed are methods for treating one or more mammalian cancers, and in particular, methods for treating human breast cancer employing one or more iNOS pathway-inhibitory compounds, either alone, or in combination with one or more selected antihypertensive agents, including calcium channel antagonists, either alone, and further in combination with one or more conventional chemotherapeutic or anti-cancer regimens. Also disclosed are particular therapeutic formulations including these compositions, and methods for their use in treating refractory, metastatic, and relapsed cancers, and for managing or reversing treatment resistance in human triple-negative breast cancers in particular.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]The present application claims priority to PCT Intl. Pat. Appl. No. PCT / US2015 / 025009; filed Apr. 8, 2015, which claims priority to U.S. Provisional Patent Application No. 61 / 976,956; filed Apr. 8, 2014, the contents of each of which is specifically incorporated herein in its entirety by express reference thereto.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT[0002]This invention was made with government support under grant R01-CA138197 awarded by the National Institutes of Health. The government has certain rights in the invention.NAMES OF THE PARTIES TO A JOINT RESEARCH AGREEMENT[0003]Not Applicable.BACKGROUND OF THE INVENTION[0004]Field of the Invention[0005]The present invention generally relates to the fields of medicine and oncology. In particular, this disclosure provides improved chemotherapeutic compositions for the treatment and / or amelioration of one or more symptoms of human cancers. In illustrative embodiments...

AI Technical Summary

Benefits of technology

The patent provides new formulations of iNOS inhibitors and their use as chemotherapy agents to treat cancer, particularly breast cancer. It also highlights the use of these inhibitors in combination with calcium channel antagonists, which can enhance their effectiveness. Additionally, the patent discusses the use of these inhibitors in altering or controlling the growth of cancer cells, either alone or in combination with calcium channel antagonists. The patent also describes how the inhibitors can be formulated and shipped in a safe and easy-to-use manner. The technical effects of this patent include providing new treatments for cancer and new methods for controlling cancer cell growth.

Problems solved by technology

Despite the significant advances in breast cancer biology, there has been limited progress in the treatment of advanced breast cancer, with little change in the overall survival for women with treatment resistant metastatic breast cancer over the last several decades.

This intratumoral heterogeneity may be a major contributor to treatment resistance and treatment failure.

TNBC is an aggressive and lethal form of cancer that lacks estrogen (ERα), progesterone (PR) and human epidermal growth factor (HER-2) receptors with no approved targeted therapeutic options.

Despite numerous advances, treatment resistance and metastasis are the main causes of death in TNBC patients.

Unfortunately, no such combinations are presently available for routine use in clinic.

Previous studies have demonstrated that high endogenous iNOS expression correlates with, and is predictive of, poor TNBC patient survival rates.

Indeed, there is still a significant unmet medical need for new agents that are effective in the treatment of hyperproliferative disorders, and particularly breast cancers that have become resistant to conventional chemotherapeutics.

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