Therapeutic use of afatinib in cancer
Inventors
SURRALLÉS CALONGE, Jordi • MINGUILLÓN PEDREÑO, Jordi • MONTANUY ESCRIBANO, Helena
Assignees
Universitat Autonoma de Barcelona UAB • Fundacio Institut de Recerca de lHospital de La Santa Creu i Sant Pau • Centro de Investigacion Biomedica en Red CIBER
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Publication Number
US-12246016-B2
Publication Date
2025-03-11
Expiration Date
Abstract
The present invention provides the afatinib or a pharmaceutically salt thereof for use in the treatment and/or prevention of a cancer in a patient suffering from a disease caused by a defect in DNA damage repair mechanism. Surprisingly, when afatinib was administered to FA cells, it was confirmed that there was a therapeutic anti-cancer effect without any toxic side-effect on DNA.
Core Innovation
Afatinib or a pharmaceutically acceptable salt thereof is disclosed for use in treating or preventing cancer in a patient suffering from a disease caused by a defect in a DNA damage repair mechanism, wherein the disease is Fanconi anemia. The disclosed cancer context includes leukemia, squamous cell carcinoma, hepatocellular carcinoma, and particularly FA-associated squamous cell carcinomas and head-and-neck squamous cancer.
The disclosure reports that afatinib does not activate the FA/BRCA pathway, including no FANCD2 ubiquitination. It also reports that afatinib does not induce DNA-toxic effects in FA cell models, including no micronuclei formation and no G2/M cell cycle arrest.
Despite the lack of FA/BRCA pathway activation and lack of DNA-toxic effects in FA cell models, afatinib inhibits growth of FA-derived head-and-neck squamous cancer xenografts in NOD-SCID mice. The disclosed results include tumor size reduction and tumor-cell selectivity over non-tumor cells, including via oral dosing.
Claims Coverage
The document includes one independent claim directed to treating cancer in a patient with Fanconi anemia by administering afatinib or a pharmaceutically acceptable salt. The independent claim is supported by dependent claims that refine the cancer type and specify afatinib salt and formulation aspects.
Treating cancer in Fanconi anemia by administering afatinib
A method for the treatment of cancer selected from leukemia, a squamous cell carcinoma, and hepatocellular carcinoma, in a patient suffering from a disease caused by a defect in DNA damage repair mechanism, wherein the disease is Fanconi anemia, comprising administering a therapeutically effective amount of afatinib or a pharmaceutical salt thereof to the patient in need thereof.
Therapeutic use for head and neck squamous cell carcinoma
The method of claim 1, wherein the cancer is head and neck squamous cell carcinoma.
Using afatinib dimaleate
The method of claim 1, wherein administering the therapeutically effective amount comprises administering an afatinib salt, wherein the afatinib salt is afatinib dimaleate.
Oral pharmaceutical composition
The method, wherein the pharmaceutical composition is an oral pharmaceutical composition.
Pharmaceutical composition with pharmaceutically acceptable excipients and/or carriers
Administering afatinib or a pharmaceutical salt thereof as a pharmaceutical composition formulated with pharmaceutically acceptable excipients and/or carriers.
The claim coverage centers on treating cancers, including squamous cell carcinoma and head-and-neck squamous cell carcinoma, in Fanconi anemia patients by administering afatinib or a pharmaceutically acceptable salt, with additional focus on afatinib dimaleate and on oral pharmaceutical composition formulated with pharmaceutically acceptable excipients and/or carriers.
Stated Advantages
Tumor growth inhibition of FA-derived HNSCC xenografts in NOD-SCID mice.
Tumor size reduction.
Tumor-cell selectivity over non-tumor cells.
No activation of the FA/BRCA pathway, including no FANCD2 ubiquitination.
No induction of DNA-toxic effects in FA cell models, including no micronuclei formation and no G2/M cell cycle arrest.
Documented Applications
Treatment of FA-associated squamous cell carcinomas and head-and-neck squamous cancer in patients suffering from Fanconi anemia.
In vivo xenograft tumor growth inhibition of FA-derived head-and-neck squamous cancer in NOD-SCID mouse xenografts following oral dosing.
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