Compositions and methods for treating cancer
Inventors
Assignees
Augusta University • Augusta University Research Institute Inc
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-9480664-B2
Publication Date
2016-11-01
Expiration Date
Abstract
Compositions containing one or more COX inhibitors in combination with one or more antagonists of 20-HETE (20-hydroxyeicosatetraeonic acid), and optionally a pharmaceutically acceptable excipient are provided. Preferred compositions include rofecoxib in combination with HET0016. The compositions have reduced side effects due to COX inhibitors. Methods for treating or inhibiting cancer using the disclosed compositions are also provided.
Core Innovation
The invention relates to a cancer-treatment strategy using a pharmaceutical composition that combines a COX-2 inhibitor with a 20-HETE antagonist. The COX-2 inhibitor is selected from celecoxib, rofecoxib, etoricoxib, valdecoxib, specified pyrazole- and sulfonamide-containing coxibs, and 2,5-dimethyl-celecoxib, while the 20-HETE antagonist is selected from WIT002, HET0016, and other specified antagonists.
The composition is described as combining COX-2 inhibition with antagonism of 20-HETE to reduce or inhibit side effects of the COX-2 inhibitor while providing anti-tumor activity. The approach is described as enhancing anti-tumor efficacy with reduced coxib-associated side effects.
Mechanistic and experimental findings in the partial content support the combination concept, including that MC38 colon cancer cells show up-regulated Cyp4a and produce 20-HETE, and that HET0016 blocks 20-HETE production. Rofecoxib suppresses COX-derived PGE2, and the combination of rofecoxib with HET0016 shows additive or increased inhibition of tumor cell proliferation and tumor growth.
Claims Coverage
The partial content provides one independent claim directed to a pharmaceutical composition for treating cancer by combining a selected COX-2 inhibitor with a selected 20-HETE antagonist, while reducing or inhibiting COX-2 inhibitor side effects. The claim includes dependent refinements specifying particular drug pairings and particular side-effect categories to be mitigated.
COX-2 inhibitor plus 20-HETE antagonist pharmaceutical composition for cancer cell growth inhibition and side-effect reduction
A pharmaceutical composition comprising an effective amount of a COX-2 inhibitor to inhibit cancer cell growth in a subject in need thereof, in combination with a 20-Hydroxyeicosatetraenoic acid (20-HETE) antagonist in an effective amount to reduce or inhibit side effects of the COX-2 inhibitor in the subject, wherein the COX-2 inhibitor and 20-HETE antagonist are selected from the listed compounds.
Across the provided independent claim, the core inventive coverage is a composition combining a selected COX-2 inhibitor with a selected 20-HETE antagonist to inhibit cancer cell growth while reducing or inhibiting COX-2 inhibitor side effects. The dependent claims further refine the coverage by specifying particular COX-2 inhibitor/20-HETE pairings and enumerating particular side-effect categories to be mitigated.
Stated Advantages
Enhances anti-tumor efficacy while reducing COX-2 inhibitor-associated side effects.
Reduces or inhibits side effects of the COX-2 inhibitor in the subject.
Provides additive or increased inhibition of tumor cell proliferation and tumor growth.
Reduces or inhibits ischemic stroke injury and bleeding and improves functional recovery.
Reduces or inhibits reoccurrence of colorectal adenoma.
Documented Applications
Inhibiting cancer cell growth in a subject in need thereof using the pharmaceutical composition.
Reducing or inhibiting cerebrovascular adverse events including ischemic stroke and bleeding, and improving functional recovery.
Reducing colorectal adenoma/cancer risk and reducing reoccurrence of colorectal adenoma in a subject by administering the pharmaceutical composition.
Reducing colorectal adenoma or polyp risk/reoccurrence in a subject, including administering after removal of a colorectal adenoma or polyp prior to administration.
Reducing or inhibiting specific side effects including myocardial infarction, arterial and venous thrombic events, ischemic stroke, and arrhythmia.
Interested in licensing this patent?