Pharmaceutical agents targeting cancer stem cells

Patent metadata

Field	Value
Publication number	US-2019091202-A1
Application number	US-201716082288-A
Country	US
Kind code	A1
Filing date	Mar 7, 2017
Priority date	Mar 7, 2016
Publication date	Mar 28, 2019
Grant date	—

Abstract

Methods for preventing or treating subjects having cancer based on the identification of pharmaceutical agents that target cancer stem cells (CSCs) have been identified. These methods include administering to the subject an effective amount of a COX2 inhibitor and an effective amount of a YAP1 inhibitor. In addition, methods of enhancing chemotherapeutic responses in cancer patients have been discovered and are described herein.

First claim

1 . A method for preventing or treating cancer in a subject comprising administering to the subject an effective amount of a COX 2 inhibitor and a YAP 1 inhibitor and preventing or treating cancer in the subject.

2 . The method of claim 1 wherein the COX 2 inhibitor is celecoxib or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

3 . The method of claim 1 wherein the YAP1 inhibitor is verteporfin, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

4 . The method of claim 1 wherein the cancer is bladder cancer.

5 . The method of claim 1 wherein the cancer is urothelial carcinoma.

6 . The method of claim 1 wherein the subject is also administered one or more other chemotherapy agents.

7 . A method for preventing or treating cancer in a subject comprising administering to the subject an effective amount of a celecoxib, or pharmaceutically acceptable salt, solvate, or stereoisomer thereof, and an effective amount of verteporfin, or pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

8 . The method of claim 7 wherein the cancer is bladder cancer.

9 . The method of claim 7 wherein the cancer is urothelial carcinoma.

10 . The method of claim 7 wherein the subject is also administered one or more other chemotherapy agents.

11 . A method of enhancing a chemotherapeutic response in a subject having cancer comprising the following steps:
a. administering an effective amount of COX2 inhibitor; b. administering an effective amount of YAP1 inhibitor; and c. administering an effective amount of a chemotherapy agent.

12 . The method of claim 11 wherein the cancer patient is administered an effective amount of COX2 inhibitor and YAP1 inhibitor prior to the administering the chemotherapy agent.

13 . The method of claim 11 wherein the cancer patient is administered an effective amount of chemotherapy agent prior to the administering of COX 2 inhibitor.

14 . The method of claim 11 wherein the COX 2 inhibitor is celecoxib or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

15 . The method of claim 11 wherein the YAP1 inhibitor is verteporfin, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

16 . The method of claim 11 wherein the cancer is bladder cancer.

17 . The method of claim 11 wherein the cancer is urothelial carcinoma.

18 . A method for preventing or treating cancer in a subject comprising administering to the subject an effective amount of a celecoxib or pharmaceutically acceptable salt, solvate, or stereoisomer thereof, verteporfin or pharmaceutically acceptable salt, solvate, or stereoisomer thereof and one or more chemotherapy agents.

19 . A method for preventing or treating cancer in a subject comprising administering to the subject an effective amount of a EP4 antagonist and a COX2 inhibitor and preventing or treating cancer in the subject.

20 . The method of claim 19 wherein the COX2 inhibitor is etodolac.

21 . A method for preventing or treating cancer in a subject comprising administering to the subject an effective amount of a EGFR inhibitor and COX 2 inhibitor and preventing or treating cancer in the subject.

22 . The method of claim 21 wherein the subject is administered a YAP1 inhibitor in addition to the EGFR inhibitor and the COX 2 inhibitor.

Assignees

• Univ Johns Hopkins

Inventors

• Hoque Mohammad O
• Sidransky David
• Oki Akira

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/407

  condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine · CPC title

• A61K31/415 Primary

  1,2-Diazoles · CPC title

• A61K31/635

  having a heterocyclic ring, e.g. sulfadiazine · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title