The approval of therapies that aim to block new blood vessel formation in tumors (a process called angiogenesis) has improved outcomes for patients with metastatic renal cell carcinoma (mRCC). However, many patients eventually stop responding, or do not respond at all, raising questions about how best to use preclinical studies to decipher mechanisms of drug resistance and optimize treatment strategies.
A significant challenge is that few, if any, preclinical models mimic all stages of metastatic disease progression and allow for comparison of treatment effects on localized primary tumors and early- and late-stage metastatic disease. A study led by John Ebos, PhD, aims to develop models of highly metastatic, treatment resistant, kidney cancer to help bridge this gap and assist in examining the role of the tumor in eventual disease progression, as well as the contribution of body (or ‘host’) as it responds to therapy.
Recent evidence suggests that some of the benefits of antiangiogenic therapy can be countered by such ‘host’ responses, and our experiments will allow for testing of compounds in clinically relevant surgical settings. This, in turn, could be used to predict (and test) additional treatment strategies to eventually improve clinical outcomes.