Mutant P53 reactivating peptides as a novel cancer therapy (No. 1672)
Lead Researcher: Prof. Varda Rotter
Newly developed p53-reactivating peptides were shown to cause regression of very aggressive tumors in several cancer models. p53 is the most important tumor suppressor gene. Mutant p53 forms can instigate a cascade of events that may lead to loss of control of cell growth and proliferation, and eventually to cancer. p53 is mutated in well over 50% of all tumors, making it the most frequently known mutated gene in human cancer. Most conventional chemotherapeutic and radio-therapeutic treatments activate p53 pathway and therefore have little effect on tumors harboring mutant-p53 forms. The p53 reactivating peptides are capable of changing the conformation of many forms of mutated p53 from mutant to wild-type form and restoring its tumor suppression functions. Hence, they have the potential to benefit up to 50% of cancer patients – patients who currently have very poor response to the conventional cancer treatments.
· A potential first line therapy for mutant p53-bearing cancers
· A potential combination treatment with Chemotherapy and other means of cancer therapy
· Suitable for treatment of about 50% of cancer patients, in which conventional treatments show poor results.
· Based on restoring the natural tumor-suppression mechanisms
The proposed technology is based on the development of peptides that are capable of changing the conformation of p53 from mutant to wild-type form and restoring its tumor suppression functions. The peptides were generated using Phage Display technique and screened so that only peptides capable of shifting the equilibrium towards the wild type conformation of p53 were selected. Preliminary pre-clinical experiments show that these p53-reactivating peptides cause regression of very aggressive tumors in several cancer models. Hence, the p53 reactivating peptides have the potential to benefit up to 50% of cancer patients – patients who currently have very poor response to the conventional cancer treatments.