# US 2018/0008564 A1 · Method of Treating Colorectal Cancers Using a PKC Inhibitor

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- Number: US 2018/0008564 A1
- Document ID: US20180008564A1
- Status: Published application
- Kind: A1
- Application number: 15/643,117
- Filed: 2017-07-06
- Published: 2018-01-11
- Earliest claimed: 2016-07-07
- Assignees: University of South Florida
- Inventors: Mildred Acevedo-Duncan
- Web page: https://patentgrep.com/patent/US20180008564A1

## CPC

- A61K 31/185: Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids (hydroxamic acids A61K31/16; peroxy acids A61K31/327)
- A61K 31/122: having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
- A61K 31/675: having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
- C12Q 1/485: {involving kinase}
- C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575)
- G01N 33/5011: {for testing antineoplastic activity}
- C12Q 2600/106: Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
- C12Q 2600/158: Expression markers
- G01N 2333/91215: with a definite EC number (2.7.1.-)
- G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
- 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)

## Abstract

The subject invention pertains to methods of treating colorectal cancer by administering an atypical PKC inhibitor. The inhibitors of aPKC useful in the methods of the instant invention include ACPD, ICA-1, DNDA and ζ-Stat. Also provided are methods of measuring the susceptibility of colon cancer cells of a subject to inhibitors of aPKCs.

## Claims

### Claim 1

A method of treating colon cancer in a patient in need thereof comprising administering a therapeutically effective amount of an atypical PKC inhibitor.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the PKC inhibitor is selected from the group consisting of ACPD, ICA-1, DNDA, and ζ-Stat.

### Claim 3 (depends on 2)

The method according to claim 2, wherein the PKC inhibitor is ζ-Stat.

### Claim 4 (depends on 1)

The method according to claim 1, wherein the subject suffers from a colon cancer that is an adenocarcinoma or a squamous cell carcinoma.

### Claim 5 (depends on 4)

The method according to claim 4, wherein the adenocarcinoma is a gastrointestinal carcinoid tumor, a gastrointestinal stromal tumor, a colorectal lymphoma, a colorectal non-Hodgkin lymphoma, a leiomyosarcoma, or a colorectal melanoma.

### Claim 6 (depends on 4)

The method according to claim 4, wherein the squamous cell carcinoma is a primary squamous cell carcinoma or a metastasis of a squamous cell carcinoma of the esophagus or the anus.

### Claim 7

A method of measuring the susceptibility of colon cancer cells of a subject suffering from colon cancer to an aPKC inhibitor, the method comprising:
obtaining a colon cell sample from a subject suffering from colon cancer, wherein the colon cell sample comprises cells suspected of being colon cancer cells and adjacent normal colon epithelial cells;
measuring the expression of an atypical PKC in the cells of the colon cell sample that are suspected of being colon cancer cells;
measuring the expression of an atypical PKC in the cells of the colon cell sample that are normal colon epithelial cells;
in the case of a higher expression of at least one atypical PKC in the cells of the colon cancer sample compared to the normal colon epithelial cells, exposing a portion of the colon cancer cells of the colon cell sample to an inhibitor of an aPKC, while leaving another portion of the colon cancer cells of the colon cell sample untreated;
measuring cell proliferation, expression and activation of aPKCs and markers of apoptosis and anti-apoptosis in treated and untreated cells;
assigning susceptibility to the colon cancer cells of the subject if the proliferation, expression and activation of aPKCs and markers of apoptosis and anti-apoptosis are reduced in treated cells compared to untreated cells.

### Claim 8 (depends on 7)

The method, according to claim 7, wherein the aPKC is PKC-ι.

### Claim 9 (depends on 7)

The method, according to claim 7, wherein the aPKC is PKC-ζ.

### Claim 10 (depends on 7)

The method, according to claim 7, wherein the activation of aPKC is the increased phosphorylation of the aPKC.

### Claim 11 (depends on 10)

The method, according to claim 10, wherein the increased phosphorylation is increased phosphorylation of PKC-ι.

### Claim 12 (depends on 10)

The method, according to claim 10, wherein the increased phosphorylation is increased phosphorylation of PKC-ζ.

### Claim 13 (depends on 7)

The method, according to claim 7, wherein the marker of apoptosis is Caspase-3.

### Claim 14 (depends on 7)

The method, according to claim 7, wherein the marker of anti-apoptosis is BCL-XL.

### Claim 15 (depends on 7)

The method, according to claim 7, wherein the marker of anti-apoptosis is survivin.

### Claim 16

A method of reducing colon cancer cell proliferation comprising administering an effective amount of an atypical PKC inhibitor to colon cancer cells.

### Claim 17 (depends on 16)

The method, according to claim 16, wherein the PKC inhibitor is selected from the group consisting of ACPD, ICA-1, DNDA, and ζ-Stat.

### Claim 18 (depends on 17)

The method according to claim 17, wherein the PKC inhibitor is ζ-Stat.

### Claim 19 (depends on 16)

The method according to claim 16, wherein the colon cancer cells are from an adenocarcinoma or a squamous cell carcinoma.
