# US 2014/0155397 A1 · Emt signatures and predictive markers and method of using the same

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- Number: US 2014/0155397 A1
- Document ID: US20140155397A1
- Status: Published application
- Kind: A1
- Application number: 14/009,208
- Filed: 2012-04-02
- Published: 2014-06-05
- Earliest claimed: 2011-04-01
- Assignees: Board of Regents
- Inventors: John V Heymach; Jing Wang; Lauren Averett Byers; Kevin R. Coombes; John D. Minna; Luc Girard
- Web page: https://patentgrep.com/patent/US20140155397A1

## CPC

- C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575)
- A61K 31/517: ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol
- G01N 33/5752: of the lungs
- C12Q 2600/106: Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
- C12Q 2600/158: Expression markers
- G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
- 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
- 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)
- 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)

## Abstract

EMT signatures and markers useful for characterizing the status of epithelial cancers and for predicting drug responses in patients having non-small cell lung cancer are provided together with methods of using the same.

## Claims

### Claim at position 1

-7. (canceled)

### Claim 8

A method for classifying an EMT status of a patient with non-small-cell lung cancer (NSCLC) comprising:
(a) obtaining a sample of the cancer;
(b) detecting an expression level in the sample of at least two nucleic acid molecules selected from the group consisting of the genes listed in Table 1; and
(c) comparing the expression level of the at least two nucleic acid molecules to a control level indicative of a known EMT status, wherein the comparison permits classifying the EMT status of the non-small-cell lung cancer in the patient as epithelial-like or mesenchymal-like.

### Claim 9 (depends on 8)

The method of claim 8, wherein the at least two nucleic acid molecules are selected from the group consisting of: VIM, AXL, F11R, GPR56, ANKRD22, ERBB3, KRTCAP3, SH3YL1, TACSTD1, MAL2, SPINT2, SCINN1A, KRT19, TNFRSF21, MUC1, EPPK1, ST14, CLDN7, TMEM125, TMC4, S100A14, TMEM30B, PRSS8, GRHL2, EPHA1, RAB25, GPR110, CDS1, CDH3, C1orf116, MAPK13, ANTXR2, TGFB1, PPARG and HMNT.

### Claim 10 (depends on 8)

The method of claim 8, wherein the control level comprises a level derived from corresponding transcripts in NSCLC samples of known classification.

### Claim 11 (depends on 8)

A method of predicting a response to treatment with an EGFR inhibitor in a patient with NSCLC, the method comprising:
(a) classifying the EMT status of the cancer according to the method of claim 8; and
(b) predicting a response to treatment with the EGFR inhibitor, wherein if the cancer is classified as epithelial-like, then it is predicted as being sensitive to the EGFR inhibitor and wherein if the cancer is classified as mesenchymal-like, then it is predicted as being resistant to the EGFR inhibitor.

### Claim 12 (depends on 11)

The method of claim 11, further comprising treating a patient having NSCLC predicted to be sensitive to the EGFR inhibitor with a therapeutically effective amount of the EGFR inhibitor.

### Claim 13 (depends on 8)

A method of treating a patient with NSCLC comprising:
(a) selecting a patient determined to comprise an epithelial-like NSCLC according to the method of claim 8; and
(b) administering a therapeutically effective amount of an EGFR inhibitor to the patient.

### Claim 14 (depends on 13)

The method of claim 13, wherein the EGFR inhibitor is erlotinib or gefitinib.

### Claim 15 (depends on 8)

A method of treating a patient with NSCLC comprising:
(a) selecting a patient determined to comprise a mesenchymal-like NSCLC according to the method of claim 8; and
(b) administering a therapeutically effective amount of an Axl inhibitor to the patient.

### Claim 16 (depends on 15)

The method of claim 15, wherein the Axl inhibitor is SGI-7079.

### Claim 17 (depends on 15)

The method of claim 15, further comprising determining an Axl expression level in a sample of the NSCLC from the patient and administering a therapeutically effective amount of an EGFR inhibitor if the Axl expression level is increased relative to a reference level.

### Claim 18 (depends on 17)

The method of claim 17, wherein the Axl expression level is an Axl protein level.

### Claim 19 (depends on 17)

The method of claim 17, wherein the Axl expression level is an Axl mRNA level.

### Claim 20 (depends on 17)

The method of claim 17, wherein the EGFR inhibitor is erlotinib or gefitinib.

### Claim 21

A method of treating a patient with NSCLC comprising:
(a) obtaining a sample of the cancer;
(b) detecting an expression level in the sample of at least one gene selected from the group consisting of: NPR3, C4orf23, LCN2, OGG1, and TRIM72;
(c) comparing the expression level of the at least one gene to a control level indicative of EGFR inhibitor sensitivity, thereby classifying NSCLC as EGFR inhibitor sensitive or resistant; and
(d) administering a therapeutically effective amount of an EGFR inhibitor to the patient if the NSCLC is classified as EGFR inhibitor sensitive.

### Claim 22 (depends on 21)

The method of claim 21, wherein the control level comprises a level derived from corresponding gene products in NSCLC samples of known EGFR inhibitor sensitivity.

### Claim 23 (depends on 21)

The method of claim 21, wherein the at least one gene is LCN2.

### Claim 24 (depends on 23)

The method of claim 23, wherein the expression level of LCN2 is determined by measuring an LCN2 mRNA level.

### Claim 25 (depends on 23)

The method of claim 23, wherein the expression level of LCN2 is determined by measuring an LCN2 protein level.

### Claim 26 (depends on 21)

The method of claim 21, wherein the EGFR inhibitor is erlotinib or gefitinib.
