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Yeda R&D Co. Ltd
Abstract ID: 1695
Cancer is the leading cause of death globally; according to the WHO, around 7 million people die from cancer every year and it is estimated that there will...
Cancer is the leading cause of death globally; according to the WHO, around 7 million people die from cancer every year and it is estimated that there will be more than 16 million new cancer cases every year by 2020. Traditional cancer treatments have largely focused on unselective ablation of dividing cells, cancer or otherwise, which often leads to significant toxic side effects in patients. Targeted cancer therapies on the other hand, attempt to inhibit one or more abnormal proteins that are found in proliferating cancer cells.
A prominent example for such abnormal cancer protein is p53, which normally plays a cardinal cancer-protective role by regulating key biological processes. When mutated, the aberrant form of p53 instigates a cascade of events that may eventually lead to the emergence of cancer. Indeed, loss of p53 activity is considered one of the hallmark features of practically all human cancers. However, no treatment has been proposed to date that can specifically and effectively target the mutant forms of p53.
We are investigating IFN beta as a treatment for mutant P53 tumours.
Cancer Associated Fibroblasts (CAFs) are sub-population of stromal cells residing adjacent to the tumour, that mediate the cancer promoting effect of the stroma. The current technology is based on the discovery finding that upon encounter with cancerous cells, CAFs activate the IFNb pathway. This IFN response was less pronounced when mutant p53 was present in the cancer cells. Unexpectedly though, exogenous application of type I IFNs was able to overcome the suppressive activity of mutant p53 and reduce its RNA and protein levels. Additionally, administering IFNb to mutant p53-bearing cancer cells exerted an inhibitory effect on their migratory capacity, which corresponds to metastatic ability. Thus, type I IFNs exert a destabilizing effect that is specific to oncogenic mutant p53, while the levels of wildtype p53 tumour suppressor remain intact.
IFNb can be used to treat patients carrying p53 mutations, thereby increasing their survival and improving their prognosis. Under this scenario, patient screening for the expression of a mutated form of p53 may serve as a diagnostic tool for successful type I IFN treatment. The invention also suggests that a chronic, low-dose therapeutic type I IFN regimen should minimize adverse effects associated with conventional IFN treatment. It also facilitates the use of IFN to prevent tumour formation in susceptible cancer patient populations that carry p53 germline mutations.
The current technology provides a simple and efficient first-in-class therapy to combat cancers that exhibit p53 mutations, by administering low doses of type I Interferon (IFN). The technology further provides means to stratify patients that are amenable for such treatment according to their tumour's p53 mutation status. Finally, a prophylactic method to chronically treat susceptible patient populations, such as subjects carrying p53 germline mutations, is presented.
Please enquire regarding licensing or codevelopment partnerships quoting reference no. 1695.
Last Updated May 2015