A new study by University of Kentucky Markey Cancer Center researchers shows that chloroquine – a drug currently used to treat malaria – may be useful in treating patients with metastatic cancers.
Published in Cell Reports, the study showed that chloroquine induced the secretion of the tumor suppressor protein Par-4 in both mouse models and in cancer patients in a clinical trial. Secreted Par-4 is essential for tumor cell death and the inhibition of tumor metastasis.
Chloroquine induces Par-4 secretion via the classical secretory pathway that requires activation of p53 (a mutation of the p53 protein, or disturbances in the pathways that signal to p53, is common in many cancers). Mechanistically, p53 directly induces Rab8b, a GTPase essential for vesicle transport of Par-4 to the plasma membrane prior to secretion. The study’s findings indicate that chloroquine induces p53- and Rab8b-dependent Par-4 secretion from normal cells for Par-4-dependent inhibition of metastatic tumor growth.
The study was led by the lab of Vivek M. Rangnekar, the Alfred Cohen endowed chair in oncology research at the UK Markey Cancer Center and a professor in the UK Department of Radiation Medicine. UK Researchers Ravshan Burikhanov and Nikhil Hebbar in Rangnekar’s group were co-... FULL STORY