Inducing cell death by hyperactivation of motility networks

Patent metadata

Field	Value
Publication number	US-10869908-B2
Application number	US-201716080975-A
Country	US
Kind code	B2
Filing date	Feb 24, 2017
Priority date	Feb 29, 2016
Publication date	Dec 22, 2020
Grant date	Dec 22, 2020

Abstract

Methods of inducing cell death by hyperactivation of motility networks are provided.

First claim

We claim:

1. A method of killing a cell with an activated motility network comprising:
stressing the cell or further activating or hyper-activating the cell's motility network,
wherein an agent or stressor is administered to the cell thereby selectively killing the cell, wherein the cell bears a mutated oncogene or mutated tumor suppressor gene, wherein the mutated gene comprises Ras, PI3K, PTEN, or another defined mutation that activates a cell migration pathway, and the agent or stressor comprises an environmental perturbation.

2. The method of claim 1 , wherein the environmental perturbation comprises a mechanical force, a temperature change, an electrical stimulus, a sound wave, osmotic shock, or other environmental change.

3. The method of claim 1 , wherein the agent comprises a statin, a phenothiazine, an antibiotic, or an analgesic.

4. The method of claim 3 , wherein the statin comprises pitavastatin, fluvastatin, atorvastatin, lovastatin, pravastatin, rosuvastatin, or simvastatin.

5. The method of claim 4 , wherein the statin comprises pitavastatin.

6. The method of claim 3 , wherein the phenothiazine comprises promazine HCl.

7. The method of claim 3 , wherein the antibiotic comprises polymyxin B sulfate or chloroxine.

8. The method of claim 3 , wherein the analgesic comprises phenazopyridine HCl.

9. The method of claim 1 , wherein the agent is administered at concentration of 5 mg/kg- 25 mg/kg.

10. The method of claim 1 , wherein the agent is administered orally, topically, or intravenously.

11. The method of claim 1 , wherein the hyper-activation is sustained.

12. The method of claim 1 , wherein the cell migration pathway comprises an oncogenic pathway or a tumor suppressor pathway.

13. The method of claim 12 , wherein the tumor suppressor pathway comprises PTEN.

14. The method of claim 12 , wherein the oncogenic pathway comprises Ras/TorC2, Rap or PI3K.

15. The method of claim 12 , wherein the cell death by hyperactivation of a motility pathway is termed sparagmosis.

16. A method of killing a cell comprising:
administering to a cell an agent or stressor that selectively kills the cell, wherein the cell bears a mutated oncogene or mutated tumor suppressor gene, wherein the mutated gene comprises Ras, PI3K, PTEN, or another defined mutation that activates a cell migration pathway, and the agent or stressor comprises an environmental perturbation.

17. The method of claim 16 , wherein the environmental perturbation comprises a mechanical force, a temperature change, an electrical stimulus, a sound wave, osmotic shock, or other environmental change.

18. The method of claim 16 , wherein the agent comprises a statin, a phenothiazine, an antibiotic, or an analgesic.

19. The method of claim 16 , wherein the agent is pitavastatin, fluvastatin, atorvastatin, lovastatin, pravastatin, rosuvastatin, or simvastatin.

20. A method of killing a cell, comprising:
treating the cell with an environmental perturbation that selectively kills the cell, wherein the cell bears a mutated oncogene or mutated tumor suppressor gene, wherein the mutated gene comprises Ras, PI3K, PTEN, or another defined mutation that activates a cell migration pathway.

21. The method of claim 20 , wherein the environmental perturbation comprises a mechanical force, a temperature change, an electrical stimulus, a sound wave, osmotic shock, or other environmental change.

Assignees

• Univ Johns Hopkins

Inventors

• Devreotes Peter
• Cai Huaqing
• Edwards Marc
• Liu Jun
• Vitolo Michele
• Lampert Thomas
• Long Yu
• Debonnes Alexandra

Classifications

• C12N2501/48

  Regulators of apoptosis · CPC title

• C12N2527/00

  Culture process characterised by the use of mechanical forces, e.g. strain, vibration · CPC title

• A61K31/22

  of acyclic acids, e.g. pravastatin · CPC title

• A61K31/366

  having six-membered rings, e.g. delta-lactones · CPC title

• A61K31/505

  Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim · CPC title