IP Library › Granted Patent US 12,318,449
Granted Patent B2
US 12,318,449 · App. 18/489,642 · Granted Jun 3, 2025

Combination therapy using riluzole to enhance tumor sensitivity to ionizing radiation

Inventors: Atif J. Khan (Monroe, NJ); Suzie Chen (Highland Park, NJ); James S. Goydos (East Brunswick, NJ); Bruce G. Haffty (Somerset, NJ)
Assignee: RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY
A61K41/0038
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Quick Facts
Patent No.
US 12,318,449
App. No.
18/489,642
Granted
Jun 3, 2025
Kind
B2
Abstract

Disclosed is a method of treating a tumor in a patient, comprising (a) administering riluzole in an amount effective to sensitize the tumor cells to ionizing radiation, and (b) irradiating the tumor cells with ionizing radiation in a dose effective to reduce tumor cell growth. The method can further comprise administering an effective amount of one or more additional therapeutic agents.

Claims (31)

1. A method of treating a tumor in a patient in need thereof, said tumor comprising cells expressing a metabotropic glutamate receptor, said method comprising:

(a) initially administering riluzole to said patient within the time window of about 24 to about 48 hours before radiation treatment,

(b) optionally, ceasing riluzole administration, and

(c) at least 24 hours following the initial treatment with riluzole, irradiating the tumor cells with a therapeutically effective dose of ionizing radiation, wherein said metabotropic glutamate receptor is metabotropic glutamate receptor 1 (mGluR1; GRM1).

2. The method of claim 1 , wherein the dose of ionizing radiation is reduced compared to the dose of ionizing radiation prescribed for tumors that are not administered riluzole.

3. The method of claim 1 , wherein the tumor is a melanoma tumor.

4. The method of claim 3 , wherein the melanoma tumor is a metastatic tumor.

5. The method of claim 4 , wherein the metastatic tumor is a cerebral metastatic tumor.

6. The method of claim 5 , wherein said ionizing radiation comprises whole-brain irradiation.

7. The method of claim 6 , wherein the dose of ionizing radiation is reduced compared to the dose of ionizing radiation prescribed for tumors that are not administered riluzole.

8. The method of claim 5 , wherein the ionizing radiation comprises fractionated whole-brain irradiation.

9. The method of claim 8 , wherein the size of the section irradiated is reduced compared to the size of irradiated sections irradiated in tumors that are not administered riluzole.

10. The method of claim 1 , wherein riluzole administration begins about 36 to about 48 hours prior to radiation treatment.

11. The method of claim 1 , wherein the last dose of riluzole before radiation treatment is administered at least 24 hours before radiation treatment.

12. The method of claim 1 , wherein riluzole administration continues until initiation of radiation treatment, or throughout radiation treatment.

13. The method of claim 1 , wherein riluzole administration continues post-radiation treatment at the same or a lower amount.

14. The method of claim 1 , further comprising administering to said patient one or more additional therapeutic agents in an amount effective to kill said tumor cells when used in combination with riluzole and ionizing radiation.

15. A method of treating a melanoma tumor in a patient in need thereof, said melanoma tumor comprising cells expressing metabotropic glutamate receptor 1 (mGluR1; GRM1), said method comprising:

(a) initially administering riluzole to said patient within the time window of about 24 to about 48 hours before radiation treatment, thereby increasing the population of tumor cells sensitive to ionizing radiation; followed by

(b) optionally, ceasing riluzole administration; and

(c) at least 24 hours following the initial treatment with riluzole, irradiating the tumor cells with ionizing radiation so that the growth of said tumor cells is reduced, thereby resulting in reduced melanoma tumor growth in said patient.

16. The method of claim 15 , wherein the dose of ionizing radiation is reduced compared to the dose of ionizing radiation prescribed for tumors that are not administered riluzole.

17. The method of claim 15 , wherein the melanoma tumor is a metastatic tumor.

18. The method of claim 17 , wherein the metastatic tumor is a cerebral metastatic tumor.

19. The method of claim 18 , wherein said ionizing radiation comprises whole-brain irradiation.

20. The method of claim 19 , wherein the dose of ionizing radiation is reduced compared to the dose of ionizing radiation prescribed for tumors that are not administered riluzole.

21. The method of claim 18 , wherein the ionizing radiation comprises fractionated whole-brain irradiation.

22. The method of claim 21 , wherein the section irradiated is reduced compared to the size of the section irradiated for tumors that are not administered riluzole.

23. The method of claim 15 , wherein riluzole administration begins about 36 to about 48 hours prior to radiation treatment.

24. The method of claim 15 , wherein the last dose of riluzole is administered at least 24 hours before radiation treatment.

25. The method of claim 15 , further comprising administering to said patient one or more additional therapeutic agents in an amount effective to kill said tumor cells when used in combination with said riluzole and said ionizing radiation.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 31, 2024
From: KHAN, ATIF J.; CHEN, SUZIE; GOYDOS, JAMES S.; HAFFTY, BRUCE G.
To: RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY
Reel/Frame 068145/0351 →
Continuity (5)
Continuation 17545559 · Dec 8, 2021
Continuation 16953559 · Nov 20, 2020
Continuation 13768544 · Feb 15, 2013
Provisional Application 61599233 · Feb 15, 2012
Related Publication 20240042033A1 · Feb 8, 2024
References Cited (30)
US 5869609A · Mulvihill · 1999 [cited by examiner]
US 6589991B1 · Lai · 2003 [cited by examiner]
US 6589998B1 · Bianchi · 2003 [cited by examiner]
US 6797692B1 · Ikonomidou · 2004 [cited by examiner]
US 6923966B2 · Rybak · 2005 [cited by examiner]
US 6998391B2 · Lyons · 2006 [cited by examiner]
US 7129073B2 · Liu · 2006 [cited by examiner]
US 7385103B2 · Chen · 2008 [cited by examiner]
US 7456267B2 · Elson · 2008 [cited by examiner]
US 7691377B2 · Goydos · 2010 [cited by examiner]
US 10864271B2 · Khan · 2020 [cited by examiner]
US 20010046491A1 · Valerie · 2001 [cited by applicant]
US 20050235366A1 · Chen · 2005 [cited by applicant]
US 20080124333A1 · Goydos et al. · 2008 [cited by applicant]
US 20100221246A1 · Goydos et al. · 2010 [cited by applicant]
WO 2010138377A1 · 2010 [cited by applicant]
Atallah et al: “Treatment of metastatic malignant melanoma.”, Current Treatment Options in Oncology, May 2005, vol. 6, No. 3, May 2005 (May 2005), pp. 185-193. [cited by applicant]
Eisen et al: “Sorafenib in advanced melanoma: a Phase II randomised discontinuation trial analysis”, British Journal of Cancer, vol. 95, No. 5, Sep. 2006 (Sep. 2006), pp. 581-586. [cited by applicant]
Green et al: “Effects fo ruluzole (RZ) and ionizing raditiaon (IR) in metabotropic glutamate receptor-1 (GRM1) positive human melanoma,” ASCO Ann Mtg proc, 2009, vol. 27, No. 15S, abs. 9083. [cited by applicant]
Haas et al: “The non-competitive metabotropic glutamate receptor-1 antagonist CPCCOEt inhibits the in vitro growth of human melanoma”, Oncology Reports, vol. 17, No. 6, Jun. 2007, pp. 1399-1404. [cited by applicant]
Khan et al: “The glutamate release inhibitor riluzole increases DNA damage and enhances cytotoxicity in human glioma cells, in vitro and in vivo”, Oncotarget, 2019, 10(29), pp. 2824-2834. [cited by applicant]
Koukourakis et al: Temozolomide with Radiation Therapy in High Grade Brain Gliomas: Pharmaceuticals Considerations and Efficacy; A Review Article; Molecules 2009, vol. 14, pp. 1561-1577. [cited by applicant]
Mantz, Jean: “Riluzole,” CNS Drug Reviews, 1996, vol. 2, No. 1, pp. 40-51. [cited by applicant]
Namkoong et al: “Metabotropic Glutamate Receptor 1 and Glutamate Signaling in Human Melanoma”, Cancer Research, Mar. 2007, vol. 67, No. 5, pp. 2298-2305. [cited by applicant]
National Cancer Institute, Definition of Antogonist, electronic resource, [http://www.cancer.gov/disctionary/?print=1&cdrid=350250], retrieved on Oct. 28, 2012. [cited by applicant]
Rzeski et al: “Glutamate antagonists limit tumor growth,” PNAS, May 22, 2001, vol. 98, No. 11, pp. 6372-6377. [cited by applicant]
Stupp et al: “Effects of Radiotherapy with Concomitant and Adjuvant Temozolomide Versus Radiotherapy Alone on Survival in Glioblastoma in a Randomised Phase III Study: 5-Year Analysis of the EORTC-NCIC Trial”, Lancet On… [cited by applicant]
Wall et al: “Riluzole is a radio-sensitizing agent in an in vivo model of braid metastatis dervived from GRM1 expressing human melanoma cells”, Pigment Cell Melanoma Res., 2015, 28(1), pp. 105-109. [cited by applicant]
Yao et al: “Enhancement of glutamate uptake mediates the neuroprotection exerted by activating group II or III metabotropic glutamate receptors on astrocytes”, Journal of Neurochemistry, 2005, vol. 92, pp. 948-961. [cited by applicant]
Zhang et al: “Sensitization of C6 glioma cells to radiation by staurosporine, a potent protein kinase C inhibitor”, Journal of Neuro-Oncology, 1993, vol. 15, pp. 1-7. [cited by applicant]