Panel Outlines Research Priorities for Kidney, Bladder Cancer

BETHESDA, Maryland—The National Cancer Institute’s Kidney/Bladder Cancer Progress Review Group has released 13 priority recommendations intended to serve as a national plan to guide research in the two diseases over the next 5 years. The recommendations cover basic and translational research, cancer control, and cancer treatment, and range from understanding the biologic mechanisms underlying the two diseases to developing innovative strategies to eradicate them.

"The priorities have an important synergy in that progress in one area will bolster progress in others," the NCI review group report said. "Supporting priorities in only one or two areas will not be enough to advance our knowledge and understanding of these cancers. We must make a commitment to research along the entire continuum."

The review group—co-chaired by Peter Jones, PhD, of the University of Southern California Cancer Research Center, and Nicholas J. Vogelzang, MD, of the University of Chicago Cancer Research Center—was one of a series of such committees appointed by former NCI director Richard D. Klausner, MD. NCI has now deferred naming any new program review groups pending an evaluation of the reports already made.

"The priorities outlined in this report are a blueprint for progress toward preventing, diagnosing, and treating kidney and bladder cancers," Dr. Jones and Dr. Vogelzang wrote in the introduction to the report.

The recommendations cover four general areas: Discovery, translational research, treatment, and cancer control.

Discovery

1. Understand the biologic mechanisms underlying the risk factors for kidney and bladder cancer phenotypes. "Novel prevention and treatment strategies may result from improved understanding of such mechanisms," the report said.

2. Identify global genetic, epigenetic, RNA expression, and proteomic alterations in tumors and place them in specific biologic pathways that are essential to development, progression, response to therapy, and maintenance of subtypes of these cancers.

3. Understand the role of stroma and intercellular signaling in organogenesis, tumor development, and maintenance of malignant phenotypes. "Most studies to date have examined only the characteristics of the tumor epithelial cells," the group noted.

4. Generate and characterize transgenic models, including conditional knock-out and knock-in strategies and orthotopic models of the diseases, focusing on the use of tissue-specific promoters and targeting human disease-related genet-
ic events. These models will allow identification and validation of prognostic, preventive, and therapeutic targets and their inhibiting agents.

Translational Research

5. Examine blood, urine, premalignant tissue, and tumor tissue before prevention and therapy trials to identify and quantify disease and identify targets for therapy and predictors and mechanisms of response, resistance, progression, and relapse.

6. Facilitate the development and util-ization of noninvasive or minimally invasive techniques to image and assess the biologic and clinical effects of targeted therapeutics. "Because kidney and metastatic bladder tumors cannot easily be sampled during therapy, noninvasive and minimally invasive methods are needed to assess therapeutic effectiveness," the report said.

7. Identify and prioritize agents—alone or in combination—that target known cancer growth and progression pathways.

Treatment

8. Develop innovative therapeutic strategies that will eradicate disease, preserve organ function, and maintain quality of life, using mechanism-based agents that take into account known prognostic variables, molecular characteristics of tumors, assays of targeted effects, surrogate markers of efficacy, and novel delivery strategies.

9. Develop and improve approaches to risk assessment of localized and advanced disease—which take into account known prognostic variables, including stage, histology, and novel molecular factors—to direct therapy.

10. Develop evidence-based, hypothesis-driven research efforts in palliative care for patients with advanced kidney and bladder cancers. "Therapy fails in 95% of patients with advanced kidney and bladder cancers," the report said.

Cancer Control

11. Describe the impact of kidney and bladder cancers and their treatment on the quality of life of individuals and their families throughout the cancer continuum, and develop and assess interventions that will reduce morbidity and improve health-related quality-of-life outcomes.

12. Identify, characterize, and validate molecular markers to determine the risk of disease, enhance early detection, and predict response to chemoprevention with new chemopreventive agents and strategies.

13. Identify and explore the gaps between barriers to standards of practice and care that currently result in disparate outcomes for kidney and bladder cancer patients. "Delay in treatment appears to be correlated with a disproportionately higher death rate among women with bladder cancer, who are diagnosed 6 to 9 months later than men," the report said. "Black men have a higher mortality rate for both bladder and kidney cancers than white men. Once the causes of these disparities are understood, strategies can be devised to remedy them." The full report can be found at http://prg.nci.nih.gov/kidney/finalreport.html.