Background:The high mobility group A proteins modulate the transcription of numerous genes by interacting with transcription factors and/or altering the structure of chromatin. These proteins are involved in both benign and malignant neoplasias as a result of several pathways. A large amount of benign human mesenchymal tumors has rearrangements of HMGA genes. On the contrary, malignant tumors show unarranged HMGA overexpression that is frequently and causally related to neoplastic cell transformation. Here, we review the function of the HMGA proteins in human neoplastic disorders, the pathways by which they contribute to carcinogenesis and the new patents focused on targeting HMGA proteins.Objective:Current review was conducted to check the involvement of HMGA as a druggable target in cancer treatment.Methods:We reviewed the most recent patents focused on targeting HMGA in cancer treatment analyzing patent literature published during the last years, including the World Intellectual Property Organization (WIPO®), United States Patent Trademark Office (USPTO®), Espacenet®, and Google Patents.Results:HMGA proteins are intriguing targets for cancer therapy and are objects of different patents based on the use of DNA aptamers, inhibitors, oncolytic viruses, antisense molecules able to block their oncogenic functions.Conclusion:Powerful strategies able to selectively interfere with HMGA expression and function could represent a helpful approach in the development of new anti-cancer therapies.