Cancer Cell Biology and Oncogenomics - John A. Copland

RhoB Signaling in Anaplastic Thyroid Carcinoma

Western blot examining induced RhoB expression in response to five different classes of drugs in anaplastic thyroid carcinoma

RhoB, a member of the Ras superfamily of isoprenylated small GTPases, is not mutated, but rather attenuated in cancer. Consequently, inducing RhoB expression in aggressive cancers, such as anaplastic thyroid carcinoma, will inhibit growth and induce cell death.

RhoB will also enhance cell death when combined with other chemotherapeutics. Upregulation of RhoB can then be used as a biomarker, as it is a key modulator for responsiveness.

In fact, preclinical data on CS-7017, a PPARγ agonist, generated in the laboratory of John A. Copland, Ph.D., led to a combinatorial clinical trial with Daiichi Sankyo. In addition to finding reagents that induce RhoB, the lab also wants to define the mechanism by which RhoB inhibits proliferation and induces apoptosis in cancer.