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An Update on Young Investigator Award (YIA) Recipient Graham Warren, MD, PhD

Dec 12, 2012

ASCO Connection recently checked in with Conquer Cancer Foundation of ASCO grant recipient Graham Warren, MD, PhD, of Roswell Park Cancer Institute. Dr. Warren received a 2008 Young Investigator Award (YIA), which provides funding to promising investigators to encourage and promote quality research in clinical oncology. In the following interview, Dr. Warren discusses the effects of nicotine on cancer therapy, the importance of smoking cessation, and the remaining questions surrounding nicotine and cancer.

AC: Why did you decide to research the effects of nicotine on cancer therapy?

Dr. Warren: Nicotine is a chemical in tobacco that is the primary agent associated with addiction, but data had shown that nicotine could increase tumor growth, angiogenesis, invasion, and decrease apoptosis. Since nicotine replacement therapy is the primary method to help people stop using tobacco, I was interested in testing the effects of nicotine on cancer treatment response.

AC: What are the results of your research? What are the biologic effects of tobacco and nicotine on cancer treatment response?

Dr. Warren: We evaluated the effects of nicotine on response to chemotherapy and radiotherapy. We used human cancer cell lines to demonstrate that nicotine decreased the effectiveness of radiotherapy and/or chemotherapy in all of the cancer cells tested. Importantly, we also showed that the effects of nicotine were important specifically when nicotine was present during treatment with radiotherapy and/or chemotherapy. This may seem like a somewhat fickle point, but proximity to treatment is important. When a cancer patient is diagnosed, treatment usually follows fairly rapidly. It is critical for us to understand if nicotine prior to treatment, during treatment, or after treatment can affect the efficacy of chemotherapy and/or radiotherapy. Our data suggest that nicotine specifically during treatment is the critical determinant of therapeutic response rather than nicotine after completion of treatment.

AC: How has your research affected patient care?

Dr. Warren: Patient care is an extremely complex topic when it comes to tobacco and nicotine. Our research has blossomed far beyond nicotine treatment in cancer cells. I am now very fortunate to be working with excellent collaborators in basic science, epidemiology, tobacco control, and clinical cancer care to better understand the broad aspects of cancer care as it relates to tobacco. Nicotine is one model by which tobacco may affect systemic response to cancer treatment through activation of systemically expressed nicotinic acetylcholine receptors present on both normal and cancerous tissue.

However, nicotine is only one of 7,000 compounds in tobacco smoke. As a result, we need to further evaluate the potential effects of nicotine on modulating therapeutic response, but we must also further understand the broader aspects of how important these observations are to clinical outcomes. For instance, I do not believe that nicotine replacement is more damaging than continued smoking in patients with cancer. Common sense dictates that nicotine replacement eliminates the other 7,000 compounds in tobacco smoke and nicotine replacement generally provides lower systemic nicotine concentrations than smoking.

Looking at the big picture, there are two fundamental clinical questions we must answer. First, does smoking cessation improve cancer treatment response and if so how long should patients quit tobacco use before starting cancer treatment? Second, how do we improve treatment outcomes in cancer patients who are unable to quit smoking prior to cancer treatment? Our results have helped pave the way for me to work with national experts to address these clinical questions.

AC: How has your research influenced the way oncologists communicate the importance of tobacco cessation to patients with cancer?

Dr. Warren: On a local level, we have taken our research and growing evidence from published literature to build a dedicated institutional tobacco assessment and cessation program available to all cancer patients. This unique program uses standardized fixed-variable tobacco assessment questions administered by nurses through the electronic medical record to accurately assess tobacco use in cancer patients. Based upon responses to specific questions, patients who are at risk for tobacco use receive information on tobacco cessation and are automatically referred to a dedicated tobacco cessation support program. The cessation program provides support to help quit tobacco use and helps patients understand the adverse effects of tobacco on cancer treatment outcomes. Through this program, we have been able to provide cessation support to more than 2,000 patients with cancer over the past 18 months. This is a truly remarkable effort that is a testimony to the dedicated efforts of nurses, physicians, midlevel practitioners, tobacco cessation counselors, and even hospital administrators to help patients with cancer quit tobacco use.

On a national scale, I have given more than 20 talks during the past few years to cancer research and treatment groups on the effects of tobacco on cancer treatment outcomes. Most of these venues include clinicians who actively participate in the care of cancer patients. The talks present the evidence of how tobacco increases treatment toxicity, decreases quality of life, and decreases survival. I discuss how tobacco and tobacco-related products increase tumor growth, angiogenesis, migration, invasion, metastasis, and decrease response to conventional cancer treatments. In addition, I discuss tobacco assessment and cessation specifically in cancer patients including the limitations of how tobacco use has been presented in the published literature. I commonly hear that many clinicians don’t realize that tobacco use is also important after a cancer diagnosis. This helps clinicians understand that it’s never too late to quit.

AC: Is there anything you’d like to highlight from your work with the American Association for Cancer (AACR) Task Force on Tobacco and Cancer?

Dr. Warren: In 2011, I was asked to be a member of the AACR Task Force on Tobacco and Cancer and have had the opportunity to work with an exceptionally talented group of individuals. We have had an extremely productive year. Led by Dr. Roy Herbst from the Smilow Cancer Center at Yale University, we hosted several talks at a Cancer Science Policy Session titled “Tobacco Use Reduces Cancer Treatment Effectiveness: Research and Policy Considerations” as a part of the 2012 AACR Annual Meeting in Chicago, IL. In addition, we presented information at an AACR-sponsored workshop at the Institutes of Medicine (IOM) titled “Reducing Tobacco-Related Cancer Incidence and Mortality: a National Cancer Policy Forum Workshop” in Washington, DC. Efforts over the past year have garnered the attention of several national organizations to help address tobacco use in cancer patients. These efforts are currently being written into AACR and IOM summary statements that will be published and available in the near future.

AC: Is there anything you’d like to highlight from your work with the Alliance Cancer Prevention Committee?

Dr. Warren: Last year, we reviewed the current state of tobacco assessment and cessation in actively accruing cooperative group clinical trials (Peters et al., J Clin Oncol. 2012). We found that less than 30% of trials assess tobacco use at any time and less than 5% assess tobacco use at follow-up. Tobacco use is a dynamic patient behavior that could alter the efficacy cancer treatment, but the lack of incorporating structured tobacco assessments into ongoing clinical trials will limit our ability to accurately understand the true effect of tobacco use and cessation on cancer treatment outcomes. We are making progress in trying to facilitate structured tobacco assessments at diagnosis and during follow-up in clinical trials, but much work has yet to be done. As a part of the Alliance Cancer Prevention Committee, we are beginning to work on efforts to track tobacco use and consider tobacco cessation support for cancer patients enrolled on clinical trials. This is very exciting because it helps merge cancer prevention with clinical cancer care. In addition, incorporating standardized tobacco assessments into clinical trials design is a model to help promote collaborative broad reaching efforts across disease sites and treatment modalities in clinical cancer research.

AC: What are some of your interests outside of oncology?

Dr. Warren: Virtually all of my time outside of work is spent trying to keep up with my wife and five kids. They certainly keep me on my toes, but they also give me a nice perspective on work. When my kids ask why people would want to keep smoking after getting cancer, I tell them “I’m not sure, but I’ll let you know as soon as I figure it out.”

AC: What has winning the YIA meant to you?

Dr. Warren: The YIA has been a springboard toward an active career as a physician scientist. The YIA provided support to generate data that was used to justify negotiating a generous startup package as a junior faculty member. Without the YIA, I would not have been able to secure lab space, get protected research time, and get mentorship support to further develop my research efforts as a faculty member.

The YIA has provided a critical foundation to pursue a career as a physician scientist. This is an extremely competitive environment and NIH funding levels are historically low making it increasingly difficult to support good research ideas. I would absolutely encourage all fellows, residents, and junior faculty to consider research in their career as this is how we make progress in treating our patients. However, to succeed in this environment, candidates must consider a dedicated mentorship plan, a supportive environment, and persistence. The YIA can provide fertile ground, but recipients must continue to ask pertinent questions, relentlessly pursue answers, and dedicate themselves to the accurate reporting of results. If you have a good question, be patient and don’t give up.
Watch Dr. Warren discuss nicotine's effect on cancer therapy, as well as how receiving a 2008 Young Investigator Award enabled him to conduct his research project.  Dr. Warren also discusses tobacco cessation after a cancer diagnosis in a Cancer.Net podcast.
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