UNM Anti-DNA Replication

About

UNM Anti-DNA Replication/Repair Cancer The American Cancer Society estimated that over 1.6 million new cases of cancer would be diagnosed and over 500,000 people would die from cancer in 2012. It is becoming more and more evident that the simultaneous or sequential attack on different aspects of cancer cell metabolism by combinations of agents is more effective than the use of a single agent. This highlights the need to develop a wide variety of therapeutic agents that hit different molecular targets in cancer cells. Despite the frequent use of agents that either damage DNA or inhibit DNA replication, there are relatively few available compounds that specifically target DNA repair and or DNA replication-related proteins. There is growing interest in the identification of DNA repair inhibitors that will enhance the cytotoxicity of DNA-damaging agents because combinations of DNA-damaging agents and DNA repair inhibitors have the potential to concomitantly increase the killing of cancer cells and reduce damage to normal tissues and cells if either the damaging agent or the inhibitor could be selectively delivered to the cancer cells. According to “Cancer Therapies: A Global Market Report” by Global Industry Analysts, the cancer therapies market will reach $162.5 Billion by 2015. Developments including improvements in characterizing and producing biological molecules make cancer therapies a promising market. This market also continues to show strong momentum due to a growing concern of national health authorities in both developed and developing countries. Companies are currently exploring advancements and improvements in drug delivery techniques opening the door for an even greater market opportunity. Additionally, technological improvements have encouraged industry to invest in new research and development projects in order to identify and validate new therapeutic drugs. Compounds that Inhibit Human DNA Ligases for Treating Cancer (8,445,537 Issued Patent and 13/864,916 Continuation Patent Application) Despite the frequent use of agents that either damage DNA or inhibit DNA replication, there are relatively few available compounds that specifically target DNA repair and or DNA replication-related proteins. There is growing interest in the identification of DNA repair inhibitors that will enhance the cytotoxicity of DNA-damaging agents because combinations of DNA-damaging agents and DNA repair inhibitors have the potential to concomitantly increase the killing of cancer cells and reduce damage to normal tissues and cells if either the damaging agent or the inhibitor could be selectively delivered to the cancer cells. Methods for treating cancer using compounds that inhibit human DNA ligases by inhibiting cell growth, killing tumorous cell and potentiating cell killing by DNA damaging agents have been developed. The DNA ligase inhibitors are anti-proliferative and potentiate the cytotoxicity of DNA damaging agents. These compounds may have clinical utility in the treatment of cancer, in particular malignancies with an altered DNA damage response. Advantages and Applications The technology platform involves inhibitors of DNA ligases that Inhibit cell growth and/or kills cells Potentiate the cytotoxic effects of many DNA damaging agents that introduce a wide variety of different types of DNA lesions May be used as research tools to identify the DNA ligase involved in different DNA transactions either in cell culture and/or in cell extract based assays Promote the understanding of genome stability and DNA repair May be used in combination with inhibitors of poly (ADP-ribose) polymerases to selectively kill therapy-resistant forms of breast cancer and leukemia Can be used in drug development for clinical cancer treatment May treat epithelial-derived cancers such as colon cancer, lung cancer, breast cancer, GI cancer, ovarian cancer and head and neck cancer as a single agent Novel Bifunctional Cancer Drugs (13/574,941 Allowed Patent and Pending Divisional Patent Application) Most cancer chemotherapy and radiation therapy kills cancer by damaging their DNA and preventing DNA replication. By increasing the ability to repair their DNA, cancer cells resist therapy, relapse and then proceed to replicate their DNA. Identifying the DNA repair proteins that cancer cells use to repair their DNA after therapy would provide new targets to improve therapy by preventing relapse. Small chemical inhibitors of those target DNA repair and replication proteins could prevent cancer cells from escaping therapy.