Project Title: Experimental therapeutics for metastatic cancer
Research overview. Metastatic disease is the primary cause of cancer mortality, but effective treatments remain elusive. Our LONG-TERM GOAL is to address the CRITICAL NEED for more targeted strategies to inhibit metastatic cancer. Metastatic cancer cells migrate away from the primary tumor and establish secondary tumors at distant sites. The Rho GTPases, Rac and Cdc42, are key molecular switches activated by a myriad of cell surface receptors to promote cancer cell migration/invasion, proliferation, and survival. However, there is a GAP IN KNOWLEDGE on the efficacy of Rac and Cdc42 inhibitors as anti-metastatic cancer therapeutics. The OBJECTIVE of this project is to characterize small molecule compounds that block the interaction of Rac and/or Cdc42 with their upstream effectors, guanine nucleotide exchange factors (GEFs), and their downstream effector P21-activated kinase (PAK) in metastatic breast and pancreatic cancer. PR CLIMB students will develop and test Rac and Cdc42 targeted small molecule compounds in non-metastatic and metastatic cancer cell lines, and noncancer cell lines. The mechanism of action will be determined for the most promising compounds using targeted mass spectrometric and protein array approaches.
Skills: PR-CLIMB participants will learn molecular biology, cell biology, and biochemistry techniques. They will culture cells and perform western blots and immunochemical experiments.
Skills: PR-CLIMB participants will learn molecular biology, cell biology, and biochemistry techniques. They will culture cells and perform western blots and immunochemical experiments.