Guidance on Provocative Questions from Ed Harlow

January 30, 2020

A message from Ed Harlow, PhD

Dear Colleagues,  

This year’s NCI Provocative Questions have just been published. I’ve listed the questions themselves below and have attached a file with the questions along with the intent paragraph to let you understand the boundaries of potential research approaches. For those of you looking for research funding or for a research challenge, these questions might be of value to you. 

PQ1: What are the underlying causes of the unexplained rising incidence in early-onset cancers?

PQ2: How does intermittent fasting affect cancer incidence, treatment response, or outcome?

PQ3: How do selective pressures affect cell competition and cooperation during cancer initiation and development?

PQ4: What mechanisms explain sex differences in cancer incidence, lesion location, or response to therapy?

PQ5: What strategies can block or reverse the emergence of new cell lineage states induced by cancer treatments?

PQ6: How can cancer cachexia be reversed?

PQ7: What methods can be developed to integrate patient-generated health data into electronic health records?

PQ8: What strategies improve and sustain coordination of comprehensive healthcare for underserved cancer patients with comorbidities?

PQ9: What methods can be developed to effectively study small or rare populations relevant to cancer research?

NCI has sponsored PQs since 2011. In the past, many of you have participated in various aspects of the Provocative Questions initiative — suggesting subjects for potential question areas, submitting applications, or reviewing; thanks for all the past support.

The applications are submitted through an RFA and this year there is $15M set aside to fund the top applications. For comparison, the success rate for past PQ applications has been similar or slightly higher than that seen for NCI's unsolicited R01 or R21 applications. There will be two submission dates for this round of PQ applications: April 30 and Nov 17, 2020 (just enough time to get a round of review comments if you happen to fall short in the first attempt). The applications request the submission of letters of intent approximately 1 month prior to the submission deadline. This is intended to help applicants make sure their submissions fulfill the PQ intent. NCI staff are available to answer questions on intent at any time and you can find the contact info in one of the FOAs. 

As a bit of background, the PQ initiative was started by Harold Varmus shortly after he became NCI Director and it is a type of grassroots funding strategy through which questions are proposed by the research community either in workshops or through online submissions. The questions highlight important areas of research that are new, under-funded, or perhaps under-appreciated. Some questions highlight particularly difficult areas of research that have been hard to approach in the past but may now be feasible because of new technologies. Successful PQ applications often require expertise in different disciplines, so they are good opportunities for multiple PI applications.

If you have any questions, feel free to send them along by return of email. If you are interested in a particular question but only have some of the needed skills to generate a great application, let me know and we’ll reach out to find new partnerships. We could also do small think tanks if people are interested (and we are quick enough in planning). 

All the best, 


Ed Harlow 
ed_harlow@hms.harvard.edu