Isothiocyanate Derivatives as Depletors of Mutant p53
Categories: “Cancer Therapeutics“
Reference #: 2011-020
Approximately 50% of all human cancers carry p53 mutations. Most mutations are within the central DNA-binding domain of p53 which disrupts its ability to bind DNA and abrogates the tumor suppressor function. In addition, tumors associated with mutant p53 are often more resistant to chemotherapy than tumors with wild-type p53. Researchers at Georgetown University have discovered that administration of isothiocyanate (ITC) derivatives can selectively deplete mutant p53 from tumor cells. Several ITC derivatives were shown to deplete mutant p53 in breast cancer, prostate cancer, colon, and oral cancer cell lines. Although the types of mutations in the cell lines vary, all of the mutations were located in the core DNA-binding domain. Wild-type p53 levels were not affected by treatment with ITC derivatives.
ITC derivatives can be used for cancer prevention and possible sensitization of previously drug-resistant cancers to chemotherapy treatments.
Isothiocyanates are found in nature (cruciferous vegetables) and derivatives may be less toxic than other cancer therapies.
ITC derivatives have been shown to selectively deplete only mutant p53.
Stage of Development
ITC derivatives are now being tested in animal models of various cancers. The most effective ITC derivatives are being further modified to optimize activity.
No references or resources available.
Provisional patent application filed