Tumor metastasis is the major cause of death in cancer patients. Thus, blocking tumor metastasis will significantly increase the survival rate of cancer patients and allow more moderate radiation or chemotherapy with less side-effects. One critical step of tumor metastasis is tumor cell migration and invasion. In this application, we focus on fascin, an actin-bundling protein, which is critical for tumor invasion and metastasis. Elevated expression of fascin is correlated with poor prognosis and short survival in cancer patients.
In specific aim 1, we will investigate the mechanism of action of fascin inhibitors.
In specific aim 2, we will further optimize fascin inhibitors.
In specific aim 3, we will use animal models to examine the efficacy and toxicity of optimized fascin inhibitors.
This proposal investigates potential therapeutics for treatment of metastatic cancer. The spread or recurrence of cancer is every cancer patient's worst fear, but unfortunately there is currently no curative treatment for cancer once it has metastasized. Therefore, there is a tremendous need for new treatments for metastatic (advanced stage) cancer.
|Huang, Jianyun; Dey, Raja; Wang, Yufeng et al. (2018) Structural Insights into the Induced-fit Inhibition of Fascin by a Small-Molecule Inhibitor. J Mol Biol 430:1324-1335|
|Syrovatkina, Viktoriya; Alegre, Kamela O; Dey, Raja et al. (2016) Regulation, Signaling, and Physiological Functions of G-Proteins. J Mol Biol 428:3850-68|