Invention:
Tiam1 is a highly conserved exchange factor that is over-expressed in many cancers, including prostate cancer (CRPCA). Increase in Tiam1 expression is associated with increased metastases and correlates with poor PCA patient survival prognosis. This patented technology has identified a novel compound which exhibits the ability to reduce prostate cancer bone metastasis by binding to the cPH domain of Tiam1 and inhibiting its cellular functions.
Background:
Prostate Cancer (PCA) is a heterogeneous disease and the 5-year survival rate for men whose cancer has metastasized at the time of diagnosis being 34%, however, if the cancer is detected prior to metastasis the 5-year survival rate increases to nearly 100%. Although most patients respond to androgen suppression by entering into clinical remission, they eventually develop more aggressive tumors that are castration-resistant PCA (CRPCA). While there are currently numerous drugs designed to inhibit metastatic cells and bone, there are currently none which target CRPCA.
Application:
- Prostate cancer - target tiam1 in order to impede tumor invasion and metastasis
Advantages:
- In vitro assays revealed that compound TPH-9 significantly reduced the number of fillipodia:
- At a concentration of 10 mM, TPH-9 prevented wound closure of PC-3 cells and invasion by 72.1±9.6%
- TPH-9 induced a tumor growth delay in a PC-3 mouse xenograft study
- Only compound which specifically targets castration-resistant prostate cancer
Patent information: issued patent #10,179,142
