The invention relates to a group of small molecules – new peptides and aptamers – able to block the action of a mutant protein, whose name is mutant p53, which is involved in many aspects of tumor development and aggressiveness. The identified molecules are able to bind and neutralize mutant p53, thus killing cancer cells that express it.
The peptides related to the invention represent a starting point to design or screen for peptido-mimetic drugs able to target and kill cancer cells which express mutant p53, to be tested in clinical trials.
The molecules related to the invention specifically recognize, bind and inhibit the tumor promoting factor mutant p53. Providing a new approach for treatment of tumors by specifically acting on mutant p53 give the advantage to develop new and very selective therapeutic strategies against tumors.
p53 mutants have an active role of in promoting tumorigenesis and different effort have been addressed to identify new strategies being able to inactivate their oncogenic function or to restore wild-type function of the protein. In this regard, researchers at the University of Trieste and LNCIB of Trieste identified a series of peptides and aptamers able to bind p53 structural and conformational mutants. In the breast cancer cell lines where the inventors tested these molecules, they acted as functional inhibitors of mutant p53-associated pro-oncogenic functions, providing the first evidences for further research and development.
The clinical implications of the invention are restricted to those tumors expressing mutant p53. However, mutations in TP53 gene are among the most frequent genetic alteration in human cancer.
File Number: PCT/EP2008/053010