Methods of treating resistant cancers

Patent metadata

Field	Value
Publication number	US-11246856-B2
Application number	US-201816614147-A
Country	US
Kind code	B2
Filing date	May 18, 2018
Priority date	May 18, 2017
Publication date	Feb 15, 2022
Grant date	Feb 15, 2022

Abstract

Provided herein is a method for reducing resistance in an individual having a drug resistant cancer, for example, a BRAF inhibitor resistant cancer. A Hippo signaling pathway inhibitor such as a Yes-associated protein 1 (YAP1) inhibitor, a Transcriptional Coactivator with PDZ-binding motif (TAZ) inhibitor, a Transcription enhancer domain (TEAD) inhibitor or a combination of these is administered. Also provided is a method of treating BRAF inhibitor resistance in an individual with a BRAF inhibitor resistant cancer, for example, malignant melanoma, with a Hippo signaling pathway inhibitor, such as Verteporfin, and a BRAF inhibitor.

First claim

What is claimed is:

1. A method of treating an individual having a BRAF inhibitor resistant melanoma consisting of:
administering to the individual having the BRAF inhibitor resistant melanoma a pharmacologically effective dose of Verteporfin and a pharmacologically effective dose of a BRAF inhibitor.

2. The method of claim 1 , wherein the Verteporfin is administered at a pharmacologically effective dose of about 1 mg/kg to about 10 mg/kg.

3. The method of claim 1 , wherein the BRAF inhibitor is vemurafenib, dabrafenib, encorafenib, methyl N-[6-[2-(5-chloro-2-methylphenyl)-1-hydroxy-3-oxoisoindol-1-yl]-1H-benzimidazol-2-yl] carbamate (BMS-098662), PLX3603, PLX4720 RAF265, and Sorafenib Tosylate.

4. The method of claim 3 , wherein the BRAF inhibitor is vemurafenib, dabrafenib or encorafenib.

5. The method of claim 1 , wherein the BRAF inhibitor is administered at a dosage of about 2 mg/kg to about 20 mg/kg.

6. The method of claim 1 , wherein the BRAF inhibitor is administered before Verteporfin, after Verteporfin or with Verteporfin.

7. The method of claim 1 , wherein the BRAF inhibitor resistant cancer has a BRAFV600 mutation, a BRAFR461 mutation, a BRAFI462 mutation, a BRAFG463 mutation, a BRAFG463 mutation, a BRAFG465 mutation, a BRAFG465 mutation, a BRAFG468 mutation, a BRAFN580 mutation, a BRAFE585 mutation, a BRAFD593 mutation, a BRAFF594 mutation, a BRAFG595 mutation, a BRAFL596 mutation, a BRAFT598 mutation, a BRAFV599 mutation, or a BRAFA727 mutation or a combination thereof.

8. The method of claim 7 , wherein the BRAF inhibitor resistant cancer has a BRAFV600E mutation, a BRAFV600K mutation, a BRAFV600D mutation or a BRAFV600R mutation.

Assignees

• Univ Maryland

Inventors

• Eckert Richard L
• Fisher Matthew
• Grun Daniel
• Adhikary Gautam
• Xu Wen

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/506

  not condensed and containing further heterocyclic rings · CPC title

• A61K31/409 Primary

  having four such rings, e.g. porphine derivatives, bilirubin, biliverdine (hemin, hematin A61K31/555) · CPC title

• A61K31/437

  the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline · CPC title

• A61K31/44

  Non condensed pyridines; Hydrogenated derivatives thereof · CPC title