It was my privilege recently to serve as Guest Editor of an issue of The Cancer Journal and its coverage of how developments in renal cell carcinoma (RCC) suggest the shape of translational research in the near future and beyond. In this issue of The Cancer Journal (Volume. 19, Number 4: July/August 2013) a distinguished group of investigators provided a road map for the next decade of development that will continue to raise the bar for improved outcomes for this population.
The publication of their work came at a particularly appropriate time, following closely the 2013 meeting of the American Society of Clinical Oncology (ASCO). Given the pace of research and the rapid evolution of treatment approaches, one of our biggest challenges—aside from managing this difficult disease itself—is keeping track of the factors impinging on our evaluation of patients, including alternative pathways of angiogenesis that are being investigated, new genetic abnormalities, including the significance of PBMR1 and BAP1 mutations and a broad spectrum of other issues.
Recent evidence, for example, suggests that epigenetic modifications and alterations in genes and their regulation are important in RCC. Another area of great excitement concerns our understanding of program death receptors, their ligands, the interplay of cytotoxic T lymphocytes, and novel therapeutic approaches. At ASCO attendees learned of the early promising results of programmed death-1 (PD-1) and PD-L1inhibitors in RCC. And one of the most dynamic directions is the future role of vaccine therapy; trials are in place using peptide pulsed vaccines or personalized immunotherapy generated through RNA-loaded dendritic cells both combined with sunitinib to both inhibit the vascular endothelial growth receptor and the tumor microenvironment to achieve sustained remissions.
As clinicians seek to gauge the impact of these analyses on their practice, the 2013 ASCO meeting and the publication of this “road map” for the next decade affords a rare opportunity, much like a snapshot of where we are now and where it appears things are headed. I suggest “appears” because the field of RCC research is much like a moving target. Just when we think we have it clearly in our sights, the landscape changes rapidly and new developments cast our strategies and perspectives in a different light. Consider, for example, the recent rejection by the FDA of the new tyrosine kinase inhibitor, tivozanib, one of the leading candidates for treatment that had been building momentum until Phase 3 data unexpectedly led to its demise in RCC. Although this was a disappointment, new trial data involving other agents suggest we are still on the threshold of possibly another era, this one involving personalized immunotherapy.
As I noted in my Guest Editor’s message in The Cancer Journal: “The future of kidney cancer therapeutics will be shepherded by the translation of many of these observations and others to the clinic. It will continue to require an innovative collaborative effort by academia, industry and patients who are challenged by this disease.” Building on the foundation of the last decade, we look toward the next decade during which new approaches will further extend the benefits of innovative treatment options for patients and their families.
Robert A. Figlin, MD