Over 50 percent of human tumors contain mutations in the gene encoding p53, a protein thought to play a role in early development of cancer. Classically, this gene is believed to suppress carcinogenic tumors by inducing a loss of function. Mutant p53, however, has recently been shown to exhibit gain-of-function properties, causing cancer formation by proliferating normally suppressed pathways. A genome-wide expression analysis identified the sterol biosynthesis pathway (e.g. mevalonate pathway) as being up-regulated by oncogenic mutant p53. This technology describes a method for treating mutant-p53-related cancers using HMG-CoA reductase inhibitors, commonly known as statins. HMG-CoA reductase is the rate-limiting enzyme in the sterol biosynthesis pathway. As such, inhibition of this pathway using statins could pave the way for entirely new treatments against mutant-p53-expressing cancers.
Unlike the conventional focus on p53-mediated oncogenesis as a loss-of-function phenomenon, this technology targets the recently observed gain-of-function noted in the sterol biosynthesis pathway. Accordingly, the technology utilizes statins, a well-studied and well-tolerated class of HMG-CoA reductase inhibitors commonly used for the treatment of high cholesterol, to inhibit the increased sterol biosynthesis found in mutant-p53-expressing cancers. In vitro, the technology was able to dramatically reduce the growth and invasiveness of breast cancer cells in 3D culture. In some cases, administration of the technology led to dramatic tumor cell death. The technology has been tested and verified on two separate breast cancer cell lines using two different types of statins
Patent Pending (WO/2012/048303)
Tech Ventures Reference: IR M11-022