# US 10,500,278 B2 · Genospecific radiosensitization

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- Number: US 10,500,278 B2
- Document ID: US10500278B2
- Status: Granted
- Kind: B2
- Application number: 14/832,159
- Filed: 2015-08-21
- Published: 2016-02-25
- Granted: 2019-12-10
- Earliest claimed: 2014-08-22
- Assignees: The Cleveland Clinic Foundation
- Applicants: The Cleveland Clinic Foundation
- Inventors: Mohamed Abazeed
- Web page: https://patentgrep.com/patent/US10500278B2

## CPC

- A61K 41/0038: {Radiosensitizing, i.e. administration of pharmaceutical agents that enhance the effect of radiotherapy (radiotherapy per se A61N5/10)}
- A61K 31/7088: Compounds having three or more nucleosides or nucleotides
- C12Q 1/6883: for diseases caused by alterations of genetic material
- G01N 33/6893: {related to diseases not provided for elsewhere}
- A61N 2005/1098: {Enhancing the effect of the particle by an injected agent or implanted device}
- C12Q 2600/156: Polymorphic or mutational markers
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B)

## Abstract

A method of treating a subject who has been diagnosed with cancer is described. The method includes characterizing the radiation-susceptibility of the subject by detecting a mutation in an NRF2 pathway protein in suitable sample obtained from the subject and treating the subject with radiation therapy if the subject is characterized as being radiation-susceptible, or treating the subject with radiation therapy and a radiosensitizing agent if the subject is characterized as being radioresistant. A method of determining if a subject has a history of tobacco smoking is also described that includes analyzing an NRF2 pathway protein to determine if a mutation is present in suitable sample obtained from the subject and characterizing the subject as having a history of tobacco smoking if a genetic fingerprint consistent with tobacco exposure is identified.

## Claims

### Claim 1

A method of treating a subject who has been diagnosed with cancer, the method comprising:
(a) analyzing a NFE2L2 pathway protein in a biological sample obtained from the subject;
(b) characterizing the subject as radiation-susceptible if the NFE2L2 pathway protein does not include a mutation, or characterizing the subject as radioresistant if the NFE2L2 pathway protein includes a mutation; and
(c) treating the subject with radiation therapy if the subject is characterized as being radiation-susceptible, or treating the subject with radiation therapy and an mTOR inhibitor if the subject is characterized as being radioresistant.

### Claim 2 (depends on 1)

The method of claim 1, wherein analyzing the NFE2L2 pathway protein further comprises determining a level of the NFE2L2 pathway protein in the biological sample obtained from the subject, wherein an elevated level of the NFE2L2 pathway protein also characterizes the subject as being radioresistant.

### Claim 3 (depends on 2)

The method of claim 2, wherein the level of NRF2 protein is determined using an immunoassay.

### Claim 4 (depends on 1)

The method of claim 1, wherein the cancer is lung adenocarcinoma.

### Claim 5 (depends on 1)

The method of claim 1, wherein the subject is human.

### Claim 6 (depends on 5)

The method of claim 5, wherein the subject has a history of long-term tobacco smoking.

### Claim 7 (depends on 1)

The method of claim 1, wherein the mutation is detected using PCR analysis.