Description:
Project ID: D2014-33
Novelty: Small drug like molecules that inhibits DNA repair factors for cisplatin (and other platinum based drugs) resistance towards solid tumors, thereby increasing cisplatin cytotoxicity and efficacy.
Value proposition: One of the limitations of chemotherapy in ovarian cancer is the innate/acquired drug resistance in cancer cells. Although increased DNA repair has been shown to be a major mechanism of cancer drug resistance, not much was done until recently to address this challenge. The researchers at The University of Toledo have discovered small drug like molecules that can overcome drug resistance to achieve better therapeutic responses in ovarian cancer. This technology could solve the long standing problem of drug resistance in cancer treatment and be universal in the treatment of all cancers treated with DNA damaging chemotherapy. The advantages of this invention are:
· It inhibits ERCC1-XPF, one of the DNA repair protein complexes, that blocks the removal of cisplatin from DNA.
· Enhances the cancer killing activity of cisplatin in cell culture models.
· Works well with other chemotherapeutic drugs such as carboplatin, oxaliplatin etc
· Can be advantageous in clinical trials and improve responses as well as survival rates in ovarian cancer patients.
Invention description: Researchers at The University of Toledo have discovered small drug like molecules that block the removal of cisplatin from DNA. Specifically, the researchers have demonstrated the use of these molecules to inhibit one of the DNA repair protein complexes ERCC1-XPF to enhance clinical responses to cisplatin and overcome drug resistance in cancer therapeutics. Earlier, these researchers demonstrated that down-regulating ERCC1-XPF enhances cisplatin efficacy in several cancer cell lines (1). Other studies in public domain are also consistent with the studies conducted by researchers at The University of Toledo and provide evidences that down-regulating ERCC1-XPF in mouse xenograft models enhances cisplatin efficacy and survival (2, 3, 4). The scientists have also developed a novel and robust fluorescence based incision assay for the further development of novel, potent and selective ERCC1-XPF inhibitors that enhance cisplatin efficacy in ovarian cancer.
Application: As chemotherapy enhancers to overcome the clinical limitation of drug resistance in ovarian and other cancers.
IP status: Patent pending
References:
1. Downregulation of XPF-ERCC1 enhances cisplatin efficacy in cancer cells.
2. Enhanced cisplatin cytotoxicity by disturbing the nucleotide excision repair pathway in ovarian cancer cell lines.
3. Identification of DNA repair gene ERCC1 as a novel target in melanoma.
4. DNA repair endonuclease ERCC1–XPF as a novel therapeutic target to overcome chemoresistance in cancer therapy.