# US 11,992,478 B2 · Methods of using androgen receptor inhibitors as cancer therapeutics > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,992,478 B2 - Document ID: US11992478B2 - Status: Granted - Kind: B2 - Application number: 17/179,801 - Filed: 2021-02-19 - Published: 2021-08-19 - Granted: 2024-05-28 - Earliest claimed: 2020-02-19 - Assignees: The Trustees of the University of Pennsylvania - Applicants: The Trustees of the University of Pennsylvania - Inventors: Todd Ridky; Christopher Natale; Cristina Aguirre Portoles - Web page: https://patentgrep.com/patent/US11992478B2 ## CPC - A61K 31/4164: 1,3-Diazoles - A61K 31/09: having two or more such linkages - A61K 31/122: having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin - A61K 31/131: acyclic - A61K 31/167: having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol - A61K 31/21: Esters, e.g. nitroglycerine, selenocyanates - A61K 31/277: having a ring, e.g. verapamil - A61K 31/4155: non condensed and containing further heterocyclic rings - A61K 31/4166: having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin - A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - 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) ## Abstract Provided herein are methods of treating cancer in a subject with a ZIP9 inhibitor. In certain embodiments, the cancerous tissues do not express the nuclear androgen receptor (AR). These methods, alone or in combination with other cancer therapies, can improve treatment outcomes in patients suffering from cancer, particularly male patients. ## Claims ### Claim 1 A method of treating or ameliorating cancer, the method comprising: administering to a subject in need thereof a composition comprising a therapeutically effective amount of at least one active agent that inhibits ZIP9, wherein the at least one active agent is bicalutamide, enzalutamide, flutamide, nilutamide, apalutamide (ARN-509), darolutamide (ODM-201), ralaniten (EPI-001), or dimethylcurcumin (ASC-J9); wherein the cancer is selected from the group consisting of squamous-cell carcinoma, basal cell carcinoma, adenocarcinoma, hepatocellular carcinomas, renal cell carcinomas, pancreatic cancer, liver cancer, colon cancer, bladder cancer, bowel cancer, kidney cancer, lung cancer, head and neck cancer, stomach cancer, leukemias, benign or malignant lymphomas, benign or malignant melanomas, myeloproliferative diseases, sarcomas, thyroid cancer, astrocytoma, esophageal cancer, carcinosarcoma, Hodgkin's disease, Wilms' tumor, and teratocarcinomas; and wherein cancerous cells in the cancer do not have detectable levels of androgen receptor (AR) as measured by immunohistochemistry relative to a known AR-expressing and AR-responsive tumor. ### Claim 2 (depends on 1) The method of claim 1, wherein the cancer is benign or malignant melanoma. ### Claim 3 (depends on 1) The method of claim 1, wherein the pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC). ### Claim 4 (depends on 1) The method of claim 1, further comprising administering an additional therapeutic agent to the subject. ### Claim 5 (depends on 4) The method of claim 4, wherein the additional therapeutic agent is administered sequentially or concurrently with the at least one active agent to the subject. ### Claim 6 (depends on 4) The method of claim 4, wherein the additional therapeutic agent is selected from the group consisting of a chemotherapeutic agent and radiation. ### Claim 7 (depends on 1) The method of claim 1, wherein the subject is male. ### Claim 8 (depends on 1) The method of claim 1, wherein the at least one active agent is administered at a lower dose than the lowest standard dose of the at least one active agent for treating a cancer that expresses AR. ### Claim 9 A method of treating or ameliorating cancer, the method comprising: identifying a subject suffering from cancer that has failed at least one prior cancer therapy, wherein cancerous cells in the cancer do not have detectable levels of androgen receptor (AR) as measured by immunohistochemistry relative to a known AR-expressing and AR-responsive tumor; wherein the cancer is selected from the group consisting of squamous-cell carcinoma, basal cell carcinoma, adenocarcinoma, hepatocellular carcinomas, renal cell carcinomas, pancreatic cancer, liver cancer, colon cancer, bladder cancer, bowel cancer, kidney cancer, lung cancer, head and neck cancer, stomach cancer, leukemias, benign or malignant lymphomas, benign or malignant melanomas, myeloproliferative diseases, sarcomas, thyroid cancer, astrocytoma, esophageal cancer, carcinosarcoma, Hodgkin's disease, Wilms' tumor, and teratocarcinomas; and administering to the subject a composition comprising a therapeutically effective amount of at least one active agent that inhibits ZIP9, wherein the at least one active agent is bicalutamide, enzalutamide, flutamide, nilutamide, apalutamide (ARN-509), darolutamide (ODM-201), ralaniten (EPI-001), or dimethylcurcumin (ASC-J9). ### Claim 10 A method of reducing proliferation of cells in a cancerous tumor, the method comprising: contacting cells in the cancerous tumor with at least one active agent that inhibits ZIP9, wherein the at least one active agent is bicalutamide, enzalutamide, flutamide, nilutamide, apalutamide (ARN-509), darolutamide (ODM-201), ralaniten (EPI-001), or dimethylcurcumin (ASC-J9); and reducing the proliferation of cells in the cancerous tumor, wherein the cells in the cancerous tumor do not have detectable levels of androgen receptor (AR) as measured by immunohistochemistry relative to a known AR expressing and AR responsive tumor; and wherein the cancer is selected from the group consisting of squamous-cell carcinoma, basal cell carcinoma, adenocarcinoma, hepatocellular carcinomas, renal cell carcinomas, pancreatic cancer, liver cancer, colon cancer, bladder cancer, bowel cancer, kidney cancer, lung cancer, head and neck cancer, stomach cancer, leukemias, benign or malignant lymphomas, benign or malignant melanomas, myeloproliferative diseases, sarcomas, thyroid cancer, astrocytoma, esophageal cancer, carcinosarcoma, Hodgkin's disease, Wilms' tumor, and teratocarcinomas. ### Claim 11 (depends on 10) The method of claim 10, wherein the cancerous tumor is melanoma. ### Claim 12 (depends on 10) The method of claim 10, wherein the cancerous tumor is pancreatic ductal adenocarcinoma (PDAC). ### Claim 13 (depends on 10) The method of claim 10, further comprising exposing cells in the cancerous tumor with an additional therapeutic agent. ### Claim 14 (depends on 13) The method of claim 13, wherein the exposing is sequential or concurrent with the contacting with the at least one active agent. ### Claim 15 (depends on 14) The method of claim 14, wherein the additional therapeutic agent is selected from the group consisting of a chemotherapeutic agent and radiation. ### Claim 16 (depends on 10) The method of claim 10, wherein the cells are male mammal cells. ### Claim 17 (depends on 16) The method of claim 16, wherein the mammal is human. ### Claim 18 A method of treating or ameliorating cancer, the method comprising: administering to a subject in need thereof a composition comprising a therapeutically effective amount of at least one active agent that inhibits ZIP9, wherein the at least one active agent is bicalutamide, enzalutamide, flutamide, nilutamide, apalutamide (ARN-509), darolutamide (ODM-201), ralaniten (EPI-001), or dimethylcurcumin (ASC-J9), wherein cells in the cancer do not have detectable levels of androgen receptor (AR) as measured by immunohistochemistry relative to a known AR expressing and AR responsive tumor; and wherein the cancer is selected from the group consisting of squamous-cell carcinoma, basal cell carcinoma, adenocarcinoma, hepatocellular carcinomas, renal cell carcinomas, pancreatic cancer, liver cancer, colon cancer, bladder cancer, bowel cancer, kidney cancer, lung cancer, head and neck cancer, stomach cancer, leukemias, benign or malignant lymphomas, benign or malignant melanomas, myeloproliferative diseases, sarcomas, thyroid cancer, astrocytoma, esophageal cancer, carcinosarcoma, Hodgkin's disease, Wilms' tumor, and teratocarcinomas. ### Claim 19 (depends on 18) The method of claim 18, wherein the cancer is benign or malignant melanoma. ### Claim 20 (depends on 18) The method of claim 18, wherein the pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC). ### Claim 21 (depends on 18) The method of claim 18, further comprising administering an additional therapeutic agent to the subject. ### Claim 22 (depends on 21) The method of claim 21, wherein the additional therapeutic agent is administered sequentially or concurrently with the at least one active agent to the subject. ### Claim 23 (depends on 22) The method of claim 22, wherein the additional therapeutic agent is selected from the group consisting of a chemotherapeutic agent and radiation. ### Claim 24 (depends on 18) The method of claim 18, wherein the subject is male. ### Claim 25 (depends on 24) The method of claim 24, wherein the subject is human.