Originally published in the 2007 ASCO Daily News
Scott M. Lippman, MD, of M. D. Anderson Cancer Center, was “amazed and thrilled” upon learning that he had been selected to receive the 2007 American Cancer Society Award in recognition of his pioneering work in cancer prevention. Dr. Lippman considers it a “privilege” to be grouped with past recipients of this “extraordinary honor.” Created in 1993, the American Cancer Society Award is designed to honor the achievements of individuals who have made noteworthy contributions to the prevention and management of cancer.
Dr. Lippman’s translational research has greatly expanded the understanding of the risk, biology and chemoprevention of carcinogenesis in various organ sites, with a particular focus on oral premalignancies. Waun Ki Hong, MD, a colleague at M. D. Anderson Cancer Center, observes that “Dr. Lippman’s work in molecularly targeted approaches for patient populations at a high risk of oral cancer has an enormous potential to reduce morbidity and mortality rates for this cancer.” Following the award presentation ceremony, Dr. Lippman will deliver his lecture, “Molecular Targeting in Microneoplasia, Where Prevention Meets Therapy,” during a Special Session to be held this afternoon (3:15 PM–4:15 PM; Room S100B, South Building).
In addition to his innovative cancer prevention research, Dr. Lippman is an active ASCO member, serving the Society in several capacities, including as a past member of the Scientific Program and Cancer Education Committees and as 2005 Chair of the Cancer Prevention Committee. He was a member of the Journal of Clinical Oncology (JCO) Editorial Board from 2003 to 2005. Dr. Lippman is a Co-chair of the upcoming Accelerating Anticancer Agent Development and Validation Workshop. ASCO is co-sponsoring this event with the American Association for Cancer Research (AACR), the Duke Comprehensive Cancer Center, the National Cancer Institute (NCI), and the U.S. Food and Drug Administration (FDA).
Q: What message do you hope to convey through your lecture?
A: The message is hope. Prevention and therapy have much in common, not least of which is the extraordinary promise of molecularly targeted drugs and their associated biology to address obstacles of each field. There is room for research that targets both prevention and therapy simultaneously, and this research may hold the key to singular advances in preventing and treating major cancers.
Q: Your lecture will address what you describe as “microneoplasia”; what is this, and how it will be a promising preventive measure?
A: I have a long-standing interest in the interface between cancer prevention and cancer therapy, which involves shared molecular alterations, risks, molecularly targeted agents and other factors. I realized that this interface occurs within a certain subclinical zone of neoplasia, a middle ground that does not belong specifically to prevention or therapy but to both. I call this middle ground “microneoplasia,” which represents microcancer and other microscopic changes that have a substantial risk of progressing into clinically evident cancer.
Q: How did you become interested in chemoprevention for head and neck cancer as a research specialty?
A: My involvement in cancer prevention began during my fellowship at the University of Arizona Cancer Center. Then I met Dr. Waun Ki Hong, who recruited me to work in his incredible head and neck and lung cancer prevention and therapy program at M. D. Anderson Cancer Center. As a medical oncologist, I have seen too much of the burden of advanced cancer and its treatment on patients, their families and the public health; I am convinced that we can learn how to lessen this burden through cancer prevention.
Q: How did your experience as a project leader within Dr. Hong’s program serve as a catalyst for your translational research endeavors in the field of prevention?
A: Dr. Hong pioneered translational cancer prevention along with others at M. D. Anderson Cancer Center. Working as a project leader with these mentors and colleagues taught me the bones of translational research. The group’s seminal discoveries inspired me to dedicate myself to translational chemoprevention and to reducing the risk, morbidity and mortality of cancer.
Q: What have been the major developments in translational chemoprevention research in the area of head and neck cancer during the last several years?
A: The major advances up to now have been in our understanding of the biology — especially the molecular biology — of head and neck carcinogenesis and in the development of molecular markers that indicate high risk for this disease. Based on translational studies in the head and neck program at my institution, assessments of loss of heterozygosity at certain chromosomal regions can identify patients with more than a 50% three-year risk of oral cancer. This ability to define high risk is critical to conducting effective chemoprevention trials. Another advance has been the identification of molecular targets for drugs that promise to prevent head and neck cancer in patients at high risk.
Q: How have you and your colleagues applied advances in our understanding of tumor biology to the development of prevention trials that are less expensive, shorter in duration and able to evaluate fewer patients?
A: Tumor biology has enabled us to identify patients at a high risk of oral cancer because of premalignant oral lesions that exhibit loss of heterozygosity at certain chromosomal locations. We developed the NCI-funded Erlotinib Prevention of Oral Cancer (EPOC) trial to evaluate such patients. EPOC is a randomized cancer-endpoint study to evaluate a molecularly targeted therapy in a small patient population (the study has a recruitment goal of only 150 patients and a planned duration of only three and a half years). By comparison in a far lower risk setting, the randomized Prostate Cancer Prevention Trial enrolled 18,882 men and took nine years to complete. The ability to define high risk has made EPOC the first cancer-endpoint study in the setting of oral premalignant lesions. EPOC is an example of personalized prevention because only people at high risk are included, allowing their low-risk counterparts — who are less likely to benefit from such treatment — to be spared any potential harmful effects of erlotinib.
I also am involved in another NCI-supported project that is using tumor biology and molecular epidemiology in an effort to reduce the scale and increase the effectiveness of future cancer-endpoint trials. This project is developing multifactorial molecular models for determining risk of high-grade prostate cancer as well as risk-benefit profiles of men with regard to moleculaly targeted agents for prostate cancer prevention. Identifying subjects at a high risk of prostate cancer will shrink the pool of candidates for future trials by increasing the placebo-arm event rate; markers that can predict drug sensitivity or resistance will help shorten future trials by increasing the treatment effect, which also limits unnecessary patient exposure to potential harmful drug effects. In addition, our Specialized Program in Research Excellence (SPORE) in head and neck cancer comprises several projects that are investigating signaling pathways — and the drugs targeting them — relevant to prevention and therapy.
Q: As the area of cancer chemoprevention continues to grow, what are some of your goals for the future?
A: I am very interested in the convergent development of molecularly targeted drugs that can be applied to cancer therapy and prevention, particularly in the lung and head and neck. The prevention-therapy convergence is based on many similarities between cancer and precancer in terms of molecular make-up, prognoses, biomarker activity in response to the same molecularly targeted agents and trial logistics such as sample size and duration. I also am keenly interested in molecular profiling that will allow for the development of personalized medicine for prevention and therapy. Such profiling can help identify people at high risk of cancer and thus with the greatest need (and tolerance) for preventive drugs; patients with early-stage cancer with poor prognoses and thus with the greatest need for adjuvant therapy; and people without or with cancer who are most likely to benefit from (or to suffer adverse effects of) particular molecularly targeted agents. Our group at M. D. Anderson Cancer Center is engaged in all of these aspects of prevention and therapy research. Increasingly over the next decade, cancer prevention should be able to include smaller-scale interventions with cancer endpoints. We will continue to conduct large-scale studies, but I believe that these trials will increasingly include correlative laboratory studies and molecular-targeted agents.
Q: How has ASCO responded to the increasing interest in cancer prevention measures?
A: ASCO has been at the forefront in promoting the science and practice of cancer prevention through several important initiatives. The Society solicits the submission of abstracts on the best prevention science for the ASCO Annual and thematic meetings. It played a crucial role in establishing cancer prevention guidelines, such as those for breast cancer risk reduction. In 2004, ASCO created the Cancer Prevention Committee, which has made several important contributions to prevention. This committee identified the Society’s major strategies and agenda for cancer prevention in a paper published in JCO.1 Finally, ASCO developed the Curriculum: Cancer Prevention, which is being released at this Annual Meeting. The curriculum is designed to enhance both fellows’ and established oncologists’ understanding of how dietary measures, smoking cessation, screening, and chemoprevention can be implemented within clinical practice to help prevent and control cancer. (See article on page 1C of this issue of ASCO Daily News for more information about this new resource.) This ASCO resource will help practicing oncology specialists to better counsel their patients about cancer prevention and to recommend or prescribe effective preventive treatments.
1. Lippman SM, Levin B, Brenner DE, et al. Cancer Prevention and the American Society of Clinical Oncology. J Clin Oncol. 2004;22:3848-3851