# US 2022/0031644 A1 · Method of treating adenoid cystic carcinoma > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2022/0031644 A1 - Document ID: US20220031644A1 - Status: Published application - Kind: A1 - Application number: 17/391,853 - Filed: 2021-08-02 - Published: 2022-02-03 - Earliest claimed: 2020-07-31 - Assignees: The Trustees of Columbia University in the City of New York - Applicants: The Trustees of Columbia University In the City of New York - Inventors: PIERO D. DALERBA; SARA VIRAGOVA - Web page: https://patentgrep.com/patent/US20220031644A1 ## CPC - A61K 31/203: Retinoic acids {; Salts thereof} - 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 The method of treating adenoid cystic carcinoma or other cancer tumors includes the administration of an effective dosage of an inverse agonist of retinoic acid receptor (RAR) or retinoid x receptor (RXR) signaling to a patient in need thereof, alone or in combination with other cancer treatment. Non-limiting examples of an inverse agonist of retinoic acid receptor (RAR) or retinoid x receptor (RXR) signaling include 4-[(1E)-2-[5,6-Dihydro-5,5-dimethyl-8-(2-phenylethynyl)-2-naphthalenyl]ethenyl]benzoic acid (commonly referred to as “BMS493”) and 4-[2-[5,6-Dihydro-5,5-dimethyl-8-(4-methylphenyl)-2-naphthalenyl] ethynyl]benzoic acid (commonly referred to as “AGN193109”). Alternatively, prior to administration of the inverse agonist of retinoic acid receptor (RAR) or retinoid x receptor (RXR) signaling, a direct agonist of retinoic acid receptor (RAR) or retinoid x receptor (RXR) signaling may be administered to the patient. Non-limiting examples of a direct agonist of retinoic acid receptor (RAR) or retinoid x receptor (RXR) signaling include all-trans retinoic acid (ATRA), isotretinoin, alitretinoin, and bexarotene. ## Claims ### Claim 1 A method of treating adenoid cystic carcinoma, comprising the step of administering an effective dosage of an inverse agonist of retinoic acid receptor (RAR) or retinoid x receptor (RXR) signaling to a patient in need thereof. ### Claim 2 (depends on 1) The method of treating adenoid cystic carcinoma as recited in claim 1, wherein the inverse agonist of retinoic acid receptor (RAR) or retinoid x receptor (RXR) signaling comprises BMS493. ### Claim 3 (depends on 1) The method of treating adenoid cystic carcinoma as recited in claim 1, wherein the inverse agonist of retinoic acid receptor (RAR) or retinoid x receptor (RXR) signaling comprises AGN193109. ### Claim 4 (depends on 1) The method of treating adenoid cystic carcinoma as recited in claim 1, further comprising the step of performing radiotherapy on the patient, either following or concurrently with the administration of the effective dosage of the inverse agonist of retinoic acid receptor (RAR) or retinoid x receptor (RXR) signaling, wherein the inverse agonist of retinoic acid receptor (RAR) or retinoid x receptor (RXR) signaling acts as a radio-sensitizer. ### Claim 5 (depends on 1) The method of treating adenoid cystic carcinoma as recited in claim 1, further comprising the step of performing chemotherapy on the patient, either following or concurrently with the administration of the effective dosage of the inverse agonist of retinoic acid receptor (RAR) or retinoid x receptor (RXR) signaling, wherein the inverse agonist of retinoic acid receptor (RAR) or retinoid x receptor (RXR) signaling acts as a chemo-sensitizer. ### Claim 6 A method of treating adenoid cystic carcinoma, comprising the steps of: administering to a patient in need thereof an effective dosage of a direct agonist of retinoic acid receptor (RAR) or retinoid x receptor (RXR) signaling, or of a combination of a direct agonist of retinoic acid receptor (RAR) and a direct agonist of retinoid x receptor (RXR) signaling; and then administering an effective dosage of an inverse agonist of retinoic acid receptor (RAR) or retinoid x receptor (RXR) signaling. ### Claim 7 (depends on 6) The method of treating adenoid cystic carcinoma as recited in claim 6, wherein the direct agonist of retinoic acid receptor (RAR) or retinoid x receptor (RXR) signaling is selected from the group consisting of ATRA, isotretinoin, alitretinoin, and bexarotene. ### Claim 8 (depends on 6) The method of treating adenoid cystic carcinoma as recited in claim 6, wherein the inverse agonist of retinoic acid receptor (RAR) or retinoid x receptor (RXR) signaling is selected from the group consisting of BMS493 and AGN193109. ### Claim 9 (depends on 1) The method of treating adenoid cystic carcinoma as recited in claim 1, wherein the patient is also administered another form of anti-tumor treatment in addition to the inverse agonist of retinoic acid receptor (RAR) or retinoid x receptor (RXR) signaling. ### Claim 10 (depends on 9) The method of treating adenoid cystic carcinoma as recited in claim 9, wherein the another form of anti-tumor treatment includes a treating agent or regimen intended to provide at least one of the group of treatments consisting of chemotherapy, radiotherapy, hormone therapy, immunotherapy, anti-angiogenic therapy, pro-differentiation therapies, such as those based on inhibition of lysine-specific de-methylases (KDMs) or isocitrate dehydrogenases (IDHs), therapies based on the inhibition of proliferative or anti-apoptotic signals mediated by tyrosine kinases, and/or therapies base on the inhibition of poly(ADP-ribose) polymerases (PARPs). ### Claim 11 (depends on 9) The method of treating adenoid cystic carcinoma as recited in claim 9, wherein the inverse agonist of retinoic acid receptor (RAR) or retinoid x receptor (RXR) comprises at least one of the group of inverse agonists comprising BMS493 and AGN193109. ### Claim 12 (depends on 10) The method of treating adenoid cystic carcinoma as recited in claim 10, wherein the inverse agonist of retinoic acid receptor (RAR) or retinoid x receptor (RXR) comprises at least one of the group of inverse agonists comprising BMS493 and AGN193109. ### Claim 13 (depends on 6) The method of treating adenoid cystic carcinoma as recited in claim 6, wherein the the patient is also administered another form of anti-tumor treatment in addition to the sequential administration of an agonist of retinoic acid receptor (RAR) or retinoid x receptor (RXR) or combination thereof, followed by an inverse agonist of retinoic acid receptor (RAR) or retinoid x receptor (RXR) signaling. ### Claim 14 (depends on 13) The method of treating adenoid cystic carcinoma as recited in claim 13, wherein the another form of anti-tumor treatment includes a treating agent or regimen intended to provide at least one of the group of treatments consisting of chemotherapy, radiotherapy, hormone therapy, immunotherapy, anti-angiogenic therapy, pro-differentiation therapies, such as those based on inhibition of lysine-specific de-methylases (KDMs) or isocitrate dehydrogenases (IDHs), therapies based on the inhibition of proliferative or anti-apoptotic signals mediated by tyrosine kinases, and/or therapies based on the inhibition of poly(ADP-ribose) polymerases (PARPs). ### Claim 15 (depends on 13) The method of treating adenoid cystic carcinoma as recited in claim 13, wherein the inverse agonist of retinoic acid receptor (RAR) or retinoid x receptor (RXR) comprises at least one of the group of inverse agonists comprising BMS493 and AGN193109. ### Claim 16 (depends on 14) The method of treating adenoid cystic carcinoma as recited in claim 14, wherein the inverse agonist of retinoic acid receptor (RAR) or retinoid x receptor (RXR) comprises at least one of the group of inverse agonists comprising BMS493 and AGN193109. ### Claim 17 A method of anti-tumor treatment comprising the step of administering an effective dosage of an inverse agonist of retinoic acid receptor (RAR) or retinoid x receptor (RXR) signaling to a patient in need thereof, wherein the tumor is associated with one or more of the following types of cancer: breast carcinomas, prostate carcinomas, pancreatic carcinomas, salivary gland carcinomas, lacrimal gland carcinomas, esophageal carcinomas, gastric carcinomas, cholangiocarcinomas and other carcinomas of the biliary tree, hepatocellular carcinomas, carcinomas of the small intestine, colon carcinomas, rectal carcinomas, carcinomas of the sweat glands, lung adenocarcinomas, ovarian carcinomas, carcinomas of the fallopian tubes, endometrial carcinomas, squamous cell carcinomas of the skin, head-and-neck district, lips, mouth, nasal sinuses, pharynx, larynx, esophagus, trachea, bronchi, lungs, uterine cervix, vagina, vulva, penis or anus, bladder carcinomas and other urothelial carcinomas of the renal pelvis, ureter or urethra, neuroendocrine carcinomas of the pancreas, small cell lung carcinomas, and renal cell carcinomas. ### Claim 18 (depends on 17) The method of anti-tumor treatment as recited in claim 17, wherein the patient is also administered another form of anti-tumor treatment in addition to the inverse agonist of retinoic acid receptor (RAR) or retinoid x receptor (RXR) signaling. ### Claim 19 (depends on 18) The method of anti-tumor treatment as recited in claim 18, wherein the another form of anti-tumor treatment includes a treating agent or regimen intended to provide at least one of the group of treatments consisting of chemotherapy, radiotherapy, hormone therapy, immunotherapy, anti-angiogenic therapy, pro-differentiation therapies, such as those based on inhibition of lysine-specific de-methylases (KDMs) or isocitrate dehydrogenases (IDHs), therapies based on the inhibition of proliferative or anti-apoptotic signals mediated by tyrosine kinases, and/or therapies based on the inhibition of poly(ADP-ribose) polymerases (PARPs). ### Claim 20 (depends on 4) The method of treating adenoid cystic carcinoma as recited in claim 4, wherein the inverse agonist of retinoic acid receptor (RAR) or retinoid x receptor (RXR) comprises BMS493, AGN193109, or a combination thereof. ### Claim 21 (depends on 5) The method of treating adenoid cystic carcinoma as recited in claim 5, wherein the inverse agonist of retinoic acid receptor (RAR) or retinoid x receptor (RXR) comprises BMS493, AGN193109, or a combination thereof. ### Claim 22 (depends on 6) The method of treating adenoid cystic carcinoma as recited in claim 6, wherein the patient is also administered another form of anti-tumor treatment in addition to the inverse agonist of retinoic acid receptor (RAR). ### Claim 23 (depends on 22) The method of treating adenoid cystic carcinoma as recited in claim 22, wherein the another form of anti-tumor treatment includes chemotherapy. ### Claim 24 (depends on 22) The method of treating adenoid cystic carcinoma as recited in claim 22, wherein the another form of anti-tumor treatment includes radiotherapy. ### Claim 25 (depends on 18) The method of anti-tumor treatment as recited in claim 18, wherein the inverse agonist of retinoic acid receptor (RAR) or retinoid x receptor (RXR) comprises BMS493, AGN193109, or a combination thereof. ### Claim 26 (depends on 17) The method of anti-tumor treatment as recited in claim 17, further comprising administering to the patient an effective dosage of the direct agonist of retinoic acid receptor (RAR) or retinoid x receptor (RXR) signaling, or of a combination thereof; and then administering an effective dosage of an inverse agonist of retinoic acid receptor (RAR) or retinoid x receptor (RXR) signaling.