How does obesity contribute to cancer risk? Why are some disseminated cancers cured by chemotherapy alone? Why do second, independent cancers occur at higher rates in patients who have survived a primary cancer than in a cancer-naïve population?

This is just a sampling of 24 vexing questions related to cancer risk, prevention, development, detection, diagnosis, and treatment that the National Cancer Institute (NCI) would like to answer through its Provocative Questions program. The brainchild of the organization's director, Harold E. Varmus, MD, the program will dole out about $15 million in fiscal year 2012 to support innovative research to examine inadequately studied observations and to better understand perplexing or paradoxical findings. The questions were compiled based on website submissions and discussions at several NCI workshops over the past year.

The workshops, which included experts in basic science, population science, and treatment and prevention, “gave everyone a chance to take a step back, survey the cancer landscape, and see what questions remained puzzling to the field,” says Jerry S.H. Lee, PhD, deputy director of NCI's Center for Strategic Scientific Initiatives. “They raised questions for which we don't have complete answers and questions that we have neglected or haven't had the technology to study.”

Researchers can apply for either a standard R01 grant or an exploratory R21 grant. Proposals, which are due November 14, must address one of the 24 questions to be considered. For more information, log on to