A novel approach to reactivate
tumor suppressor p53
p53 aggregation is linked to cancer
The protein p53 plays a key role in preventing cells in the body from becoming cancerous. Hence, mutations in p53 that inactivate the protein often lead to cancer formation. Recently, half or more of the known mutations in p53 have been shown to cause instability in the protein structure that can lead to its aggregation. This class of structural mutations is found in many types of cancers and predominates in ovarian, colorectal, and lung tumors. Deposits of aggregated p53 are broadly found in these and other cancers, and are linked to particularly aggressive tumor types. The long-term survival of cancer patients with mutations that lead to aggregation of p53 is significantly lower than those without mutations. This presents a novel mechanism of p53 dysfunction which we are targeting for therapeutic intervention.
Breast Cancer Tumor Sample Showing No Detectable p53 Expression
Breast Cancer Tumor Sample Showing
Highly Elevated p53 Expression
p53 reactivator kills cancer cells in culture
and tumors in animal models
ReACp53 (Reactivator of p53) is a peptide aggregation inhibitor evolved from the pioneering studies of protein aggregation and inhibitor design by ADRx founder David Eisenberg (UCLA). Experiments have shown that ReACp53 kills mutant-p53 cancer cells from nine different tumor tissues. ReACp53 reduces cytosolic p53 deposits and induces the appearance of diffuse nuclear p53, regulates downstream targets of p53. ReACp53 is also active in vivo. Initial studies in mouse xenograft models of ovarian cancer showed that daily treatment with ReACp53 prevented or eliminated subcutaneous and disseminated tumors. These findings encourage development of ReACp53 as a cancer therapeutic.
ADRx has the exclusive license to the patent that describes and claims p53 aggregation inhibitors and specifically the lead candidate, ReACp53. ADRx is developing a new generation of ReACp53 with improved efficacy and delivery strategies for multiple cancers.