Ongoing Research

Prevention of cancer can occur in several ways, but certainly tobacco-caused illnesses are the single most preventable cause of death and disability in our society. Thus, researchers in the Cancer Prevention and Control Program (CPC) are involved in a number of primary prevention research projects that address the treatment of tobacco dependence. Mayo Clinic is home to the widely-recognized Nicotine Dependence Center, directed by Richard Hurt, M.D., and devoted to identifying ways to ameliorate the single most important cause of cancer - the use of tobacco. The Nicotine Dependence Center has a fully operationalized Research Program, Education Program, and Treatment Program, with a combined staff of over 40 people. In addition, a number of important symptom control trials are conducted by Mayo Clinic Cancer Center, many of which fall under the auspices of the North Central Cancer Treatment Group (NCCTG), and which effort is led by Charles Loprinzi, M.D. Further, under the leadership of Paul Limburg, M.D., Mayo's chemoprevention research efforts continue to grow.

The current ongoing research efforts fall under each of the three Program aims and are described more thoroughly in the following pages:

• Chemoprevention Research
• Symptom Control and Side Effect Research
• Tobacco Dependence Research

These efforts are conducted through a number of intra- and inter-programmatic interactions that contribute to the success of the Cancer Prevent Program.

For example, tobacco dependence activities are very inclusive as tobacco use cuts across all disciplines. Investigators from the Nicotine Dependence Center have collaborative research with investigators from the Genetic Epidemiology and Risk Assessment (GERA) Program (Yolanda Garces, M.D. and Jon Ebbert, M.D.) and the Women's Cancer Program (Gary Croghan, M.D., Ph.D.), in the Cancer Center and have begun a new collaboration (Drs. Hurt and Ebbert) with Steven Ekker, Ph.D. of the Cell Biology Program, to use the zebrafish model to identify a biomarker for the sensitization of the nicotine receptor and elucidate the fundamental basis for nicotine dependence. Program members also have collaborative relationships with researchers in other departments and divisions at Mayo.

A collaboration between Dr. Limburg and James Jett, M.D. is seeks to facilitate identification and recruitment of cigarette smokers for a Cancer Prevention Network (CPN)-sponsored lung cancer chemoprevention trial. In addition the nicotine research staff are assisting David Warner, M.D., director of the Anesthesia Clinical Research Unit, to identify and recruit smokers for his R03 grant, "Elective Surgery as a Teachable Moment for Smoking Cessation," R03 CA R6371.

Other ongoing tobacco dependence-related collaborations include Dr. Ebbert's interaction with the genetic epidemiologists in GERA (Ping Yang, M.D., Ph.D., and James Cerhan, M.D., Ph.D.); and Steven Ames, Ph.D., as a co-investigator on a prostate cancer project providing support for the behavioral aspects of that project.

As the Program moves forward, researchers continue to try to develop better therapies are certainly needed to treat tobacco-dependent patients, and to seek to prevent the onset of tobacco-related diseases. These efforts are mediated through effective interventions for tobacco users. Expanding the Program's reach is an important component of this research, and Mayo Clinic is pursuing a number of options, including recruiting a behavioral scientist in Jacksonville, Fla., with expertise in tobacco research and in populations with health disparities. This will build on the already successful efforts of Dr. Ames, who, in collaboration with Chudley Werch, Ph.D., at the University of Florida, has developed a sustained line of tobacco research in young adults.

Other initiatives include expanding collaborations with tobacco researchers at the University of Minnesota through collaborative grant submissions and a proposal for a Tobacco Policy and Research Center supported by Mayo and the Academic Health Center Leadership at the University. Investigators are exploring research collaborations with tobacco researchers at the University of Arizona Cancer Center.

Mayo Clinic's chemoprevention activities include multiple groups within the Cancer Center, the NCCTG and beyond, as evidenced by direct interactions with the Women's Cancer, Developmental Therapeutics, Prostate Cancer, Gastrointestinal Cancer and GERA programs. Dr. Limburg's work with the Hormel Institute involves a regional collaboration that is anticipated to identify and bring an array of novel chemoprevention agents to future clinical trials.

Chemoprevention investigators are actively designing clinical trials across the full spectrum of anti-cancer agent development. Dr. Limburg, Joel Reid, Ph.D., and others anticipate further pursuit of novel chemoprevention compounds through preclinical studies conducted at Mayo Clinic, and in collaboration with investigators at the Hormel Institute, as well as in Phase 0, I, II, and ultimately Phase III clinical trials. Additional formulations expertise from investigators at the Center for Drug Delivery Research at the University of Kansas (a member of the Cancer Prevention Network) will also be a valuable asset.

Other research priorities include focused attention on plant-based compounds will be viewed as a high priority. Biomarker discovery efforts in the laboratories of Frank Sinicrope, M.D., and Navtej Buttar, M.D., should facilitate continued expansion of the molecular targets that can be applied in early phase clinical trials. In particular, characterization of the applicability of rectal aberrant crypt foci as an intermediate marker for colorectal cancer risk is expected, along with new insights into the growth regulation and malignant transformation in Barrett's esophagus. Ongoing interactions with investigators from the GERA program may also facilitate improved risk stratification, thereby affording definition of enriched patient populations for whom chemoprevention strategies may be more clinically meaningful.

The symptom control program involves a variety of researchers from many fields, including medical oncology, radiation oncology, surgical oncology, nursing oncology, gastroenterology, physical medicine, general internal medicine, complimentary and alternative therapy, and psychiatry. These participants come from a number of other Cancer Center Programs including Gastrointestinal Cancer (e.g. Axel Grothey, M.D., for oxaliplatin neuropathy), Hematologic Malignancies (e.g. David Steensma, M.D. and Thomas Witzig, M.D., for anemia studies), Women's Cancer (e.g. Edith Perez, M.D., for osteoporosis studies), Cancer Imaging (e.g. Matthew Callstrom, M.D., for cryoablation of painful bone lesions), and Developmental Therapeutics (e.g. Matthew Ames, Ph.D., and Matthew Goetz, M.D., for pharmacogenomics issues with hot flash studies).

Mayo Clinic Cancer Center symptom control investigators have, in recent past, conducted and published more clinical trials contributing to practice changes than any other research group related to the following prominent clinical problems suffered by patients with cancer: cancer anorexia/cachexia, cytotoxic therapy-induced gastrointestinal mucositis, and hot flashes related to cancer therapy (and/or related to the denial of hormonal therapy for treatment of such symptoms in patients with a cancer history). The investigators plan to continue their present productivity by completing current work and continuing to expand the portfolio.