Combinatorial compositions and methods for treatment of melanoma

Patent metadata

Field	Value
Publication number	US-9937161-B2
Application number	US-201414770994-A
Country	US
Kind code	B2
Filing date	Mar 6, 2014
Priority date	Mar 6, 2013
Publication date	Apr 10, 2018
Grant date	Apr 10, 2018

Abstract

Embodiments described here are combinatorial compositions and methods using these compositions for treating melanomas having activated mutations. The compositions comprises combinations of inhibitors of a MAPK pathway, ERK inhibitors, EGFR inhibitors, oxidative phosphorylation (OXPHOS) inhibitors, inhibitors of B-Raf, mitochondrial inhibitors, c-KIT inhibitors, MEK inhibitors and tigecycline or a derivative thereof.

First claim

What is claimed:

1. A method for treating melanoma in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a composition consisting of:
(a) at least one inhibitor of B-Raf consisting of vemurafenib, GDC-0879, PLX-4720, Sorafenib Tosylate, Regorafenib, RAF265 and derivatives, NVP-BHG712, AZ628, ZM 336372, SB590885, dabrafenib, and LGX818; and
(b) at least one mitochondrial inhibitor consisting of oligomycin, malonate, oxaloacetate, barbiturates, rotenone, antimycin-A, arsenate, NV-128, ME-344, TTFA, rotenone, 2,4-Dinitrophenol (DNP), and oligomycin A in a pharmaceutically acceptable carrier,
wherein the melanoma comprises at least one mutation in the B-RAF gene therein.

2. The method of claim 1 , wherein the inhibitor of B-Raf is PLX-4720 and the mitochondrial inhibitor is DNP.

3. The method of claim 1 , further comprising selecting a subject who has been diagnosed with melanoma.

4. The method of claim 1 , wherein the at least one B-RAF gene mutation is a substitution of valine at the 600 amino acid residue of the encoded B-Raf polypeptide.

5. The method of claim 4 , wherein the substitution is selected from the group consisting of V600E, V600D, V600K and V600R.

Assignees

• Massachusetts Gen Hospital
• Brigham & Womens Hospital Inc

Inventors

• Haq Rizwan
• Fisher David E
• Widlund Hans Ragnar

Classifications

• G01N33/5751

  of the skin, e.g. melanoma · CPC title

• C12Q2600/158

  Expression markers · CPC title

• C12Q1/6886

  for cancer (immunoassay for cancer G01N33/575) · CPC title

• A61K31/06

  the aromatic ring being substituted by nitro groups · CPC title

• A61K31/44

  Non condensed pyridines; Hydrogenated derivatives thereof · CPC title