Abstract PP01-01: A funny thing happened to me while trying to cure ovarian cancer; I became a cancer prevention research specialist

Abstract

Abstract First, I want to thank Dr. Marge Foti and the AACR Administration and Members for continuing to provide such an outstanding forum for research presentations, education and training. My AACR Membership # is 28, so you can intuit that I am as, “old as the hills.” I started my working career as a summer concrete finisher in Milwaukee in 1960, earning $2.50 an hour. In May, 1962 just as was to start my 3rd “tour” on a concrete team, I received a call from my first cousin, Dr. Bruce Alberts, a Harvard biophysicist (who later in life became President of the National Academy of Science, and the Editor in Chief of the Journal, SCIENCE), offering me a research specialist position in Harvard's Conant Labs, studying how DNA strands anneal after replication. I, of course said, “No thank you, “ because this Harvard summer position only paid the minimum wage of $1/ hour. But then, I scratched my head, and thought, maybe this opportunity would lead to a career in scientific research? The summers of 1962 and 1963 were the key that truly opened my mind to a lifetime career in translational research. I worked with Helga and Paul Doty, down the hall from cousin, Bruce, and one floor above James Watson! So, LESSON # 1: Take advantage of every opportunity to “learn “throughout your academic career, no matter what the personal sacrifice. In the “Cold/Ice Cold” Madison, Wisconsin Winter of 1966/ 1967, while completing an internal medicine and surgical internship, I earned $3,000 and was “buttonholed” to work 6 months on the UW Surgical Oncology Unit which was affectionately dubbed, “Poisoner's Paradise,” or “5FU For Everyone!” As a young “squirter,” I became hooked on oncology, and especially, the management of non-melanoma skin cancer, serving a 3 month stint with the originator of Mohs surgery, Dr. Fred Mohs. My Dad was admitted to my Service with recurrent squamous cell head and neck cancer, invasive into the mandible and refused “commando surgery.” Fred used his developing skills to “dig” into my dad's jaw and provide a “miracle” cure! Who wouldn't be “hooked!” So, I applied for a Clinical Associate Oncology Fellowship at NCI. Parenthetically, I had an extremely low Draft Lottery # and was a few months away from an “all expenses paid trip to Vietnam!” Amazingly, I was offered a highly coveted Fellowship on the NCI Leukemia Service at their Baltimore Cancer Research Center (BCRC). In the first week I was handed a red powder and told to develop an analytical assay, perform preclinical toxicology in rats, and write and complete a phase 1 clinical trial in 2 years. When I said I could accomplish these tasks, minus the rat studies, the Director of the BCRC said, “You are going to Vietnam with the Coast Guard.” So, I became a “rat doctor!” I completed all research steps and was rewarded with a trip to San Francisco in May, 1969 to deliver an AACR Plenary Session talk to an audience of about 250 on, “The Pharmacokinetics of Daunorubicin in Man.” By chance alone, Dr Sydney Salmon (who later became the first Director of the University of Arizona Cancer Center) gave a multiple myeloma presentation just before me. On the spot, he offered me a faculty position in the UCSF Cancer Center for January, 1971. So, LESSON # 2: “Be at the right place at the right time, “and always be willing to do the “rat experiments!” In 1971 at UCSF, as an Instructor in Medicine in the Cancer Center, I was assigned a bright eyed, bushy tailed fourth year medical student named Frank L. Meyskens, Jr. We became friends and in 1974 as an Assistant Professor, I was an Attending Physician on a Medicine Service with Dr. Meyskens as the Resident and a “whippersnapper” intern, Dr. Daniel Von Hoff. Three years later I helped to recruit Dr. Meyskens to the Section of Hematology and Oncology, University of Arizona Cancer Center (UACC) and 15 years later, I helped recruit Dr. Von Hoff to be the second Director of the UACC. In 1980, I teamed with Dr. Meyskens to initiate an NCI Program Project Grant named, “Vitamin A and Cancer,” which currently is called, “Chemoprevention of Skin Cancer Program Project,” and is in year 33, scheduled to go to year 36 in 2016. And, so started our interest in cancer chemoprevention and non-melanoma skin cancer as a model for the development of molecularly targeted, topically and, systemically administered drugs. In 1989, when Dr. Meyskens became Director of the Chao Family Cancer Center, I was asked to strengthen our fledgling Cancer Prevention and Control Program to satisfy the new guidelines for Comprehensive status for NCI Cancer Centers. So, I sent an SOS across the UA Campus, asking for interested faculty to come to an organizational meeting. Four senior, UA Faculty responded to my urgent alert; two basic and translational scientists, Drs. Tim Bowden (a skin and prostate carcinogenesis specialist) and Gene Gerner (a colon carcinogenesis specialist), a behavioral scientist, Dr. Cheryl Ritenbaugh (a clinical anthropologist), and an experienced biostatistician, Dr. Thomas Moon (a clinical trials specialist). With this cancer prevention clan of five, we fashioned 3 NCI-funded Program Projects (Skin and Colon Cancer Prevention), competed successfully for a Chemoprevention Drug Phase 1/2 Contract and started T32 and R25 Cancer Prevention and Control Training Grants. These initiatives resulted in the completion of five phase 3 cancer prevention trials, countless phase 2 clinical and translational research studies and a treasure chest of exciting, NCI-DCP-funded , senior faculty (e.g. Drs. Robert Dorr, Gary Goodman, Ana Maria Lopez , Anna Giuliano, Scott Lippman, Sue Gapstur, Cyndi Thompson, Janine Einspahr, Elena Martinez , Mary Reid, Steve Stratton, Sherry Chow, Lois Loescher, Beth Jacobs, Patricia Thompson , Clara Curiel). The developing tragedy is that the bridge from R25 to K07/K08/ K01 to R01 in cancer prevention is in great disrepair (i.e. looking like the San Francisco Bay Bridge immediately after the 1989 earthquake!!) and the prospects for renovation are dwindling. So, LESSON # 3: When you see a disaster about to happen, be a “stand up” person and don't run in the opposite direction! As a community of Cancer Preventionists, we must work together toward a common goal to help our colleagues, young and old alike stay engaged in cancer prevention and control research careers. As an AACR membership group, I suggest we set up a focused meeting to sit alongside our NCI -DCP colleagues and discuss how we can rescue our research field at this time of great peril. One thing is certain, if we neglect our next generation of cancer prevention scholars, the opportunities for major reductions in both cancer incidence and mortality will be greatly impacted. There can be no better gift than to be a highly successful mentor. The rewards” return 10-fold!” Not only are great mentors blessed with success in their own research careers, but the Mentees become “family!” During my 45 years as a clinical and translational researcher I have been blessed with outstanding mentees, so much so that it is hard to decipher, “who is the Mentor and who is the Mentee?” And my “family” now numbers in the hundreds. Listed below, are “Mentees” and representative research projects that I will discuss to some degree in my presentation, as examples of “mentored” research that has evolved from the Cancer Prevention and Control Program that Dr. Meyskens and I started more than 30 years ago in the University of Arizona Cancer Center and that has been “transplanted” many times to many other NCI-designated Comprehensive Cancer Centers: Frank L. Meyskens, Jr., M.D.: Professor of Medicine, Chair of Cancer Control Research Committee, SWOG, and Director Emeritus, Chao Family Cancer Center, Univ. California-Irvine. (Meyskens FL Jr, Emerson SS, Pelot D, Meshkinpour H, Shassetz LR, Einspahr J, Alberts DS, Gerner EW. Dose de-escalation chemoprevention trial of -difluoromethylornithine in patients with colon polyps. J Natl Cancer Inst 86:1122-30, 1994). Robert T. Dorr, Ph.D., R.P.H.: Professor of Pharmacology, Univ. Arizona Cancer Center. (Dorr RT, Ertl G, Levine N, Brooks C, Bangert JL, Powell MB, Humphrey S, Albers DS. Effects of a superpotent melanotropic peptide in combination with solar ultraviolet radiation on tanning of the skin in human volunteers. Arch Dermatol 140:827-35, 2004). Gary Goodman, M.D.: Joint Member, Fred Hutchinson Cancer Center. (Goodman G, Meyskens F, Alberts DS: Retinol, vitamins and cancer prevention, 25 years of learning and relearning. J Clin Oncol 26(34):5495-5496, 2008). Scott Lippman, M.D.: Director, Moores Cancer Center, Univ. California-San Diego and Editor-in-Chief, Cancer Prevention Research. (Lippman SM, Alberts DS, Slymen DJ, Weiner S, Aristizabal SA, Luditch A, Davis JR, Surwit EA. Second-look laparotomy in epithelial ovarian carcinoma: prognostic factors associated with survival duration. Cancer 61:2571-7, 1988). Susan M. Gapstur, Ph.D., M.P.H.: Vice President, American Cancer Society, Atlanta, GA. (Jacobs ET, Martinez ME, Alberts DS, Ashbeck EL, Gapstur SM, Lance P, Thompson PA. Plasma insulin-like growth factor I is inversely associated with colorectal adenoma recurrence: a novel hypothesis. Cancer Epidemiol Biomarkers Prev 17(2):300-5, 2008). Ana Maria Lopez, M.D., M.P.H.: Professor of Medicine and Pathology, Medical Director, Arizona Telemedicine Program, University of Arizona. (Lopez AM, Wallace L, Dorr RT, Koff M, Hersh EM, Alberts DS. Topical DMSO treatment for pegylated liposomal doxorubicin-induced palmar-plantar erythrodysesthesia. Cancer Chemother Pharmacol 44:303-6, 1999). Robin Harris, Ph.D.: Professor of Epidemiology and Public Health, University of Arizona. (Harris RB, Foote JA, Hakim IA, Bronson DL, Alberts DS. Fatty acid composition of red blood cell membranes and risk of squamous cell carcinoma of the skin. Cancer Epidemiol Biomarkers Prev 14(4):906-12, 2005). Anna Giuliano, Ph.D.: Director, Center for Infection Research in Cancer, Moffitt Cancer Center. (Sedjo RL, Ranger-Moore J, Foote J, Craft NE, Alberts DS, Xu MJ, Giuliano AR. Circulating endogenous retinoic acid concentrations among participants enrolled in a randomized placebo-controlled clinical trial of retinyl palmitate. Cancer Epidemiol Biomarkers Prev 13(11):1687-92, 2004). H.H. “Sherry” Chow, Ph.D.: Professor of Medicine and Pharmacy and Prinicipal Investigator, University of Arizona Cancer Center, Phase I/II Chemoprevention Consortium. (Chow, HH, Garland L, Hsu CH, Vining DR, Chew WM, Miller JA, Perloff M, Crowell JA, Alberts DS. Resveratrol modulates drug and carcinogen metabolizing enzymes in a healthy volunteer study. Cancer Prev Res 3(9) 1168-75, 2010). Steven P. Stratton, Ph.D.: Associate Professor of Medicine and Director, Scientific Review Committee, University of Arizona Cancer Center. (Stratton SP, Saboda KL, Myrdal PB, Gupta A, McKenzie NE, Brooks C, Salasche SJ, Warneke JA, Ranger-Moore J, Bozzo PD, Blanchard J, Einspahr JG, Dorr RT, Levine N, Alberts DS. Phase I study of topical perillyl alcohol cream for chemoprevention of skin cancer. Nutr Cancer 60(3):325-30, 2008). Mary E. Reid, Ph.D.: Associate Professor of Oncology, Director of Collaborative Research, Department of Medicine, Roswell Park Cancer Center. (Reid M, Duffield-Lillico AJ, Slate E, Natarajan N, Turnbull B, Jacobs E, Combs Jr., GF, Alberts DS, Clark L and Marshall JR. The nutritional prevention of cancer: 400 mcg per day selenium treatment. Nutr Cancer 60(2):155-63, 2008). James R. Marshall, Ph.D.: Sr. Vice President for Cancer Prevention and Population Sciences; Chair, Dept. of Cancer Prevention and Population Sciences, Roswell Park Cancer Institute. (Marshall J, Tangen C, Sakr W, Wood D, Berry D, Klein E, Lippman S, Parnes H, Alberts D, Jarrard D, Lee WR, Crawford ED, Ely B, Ray M, Davis W, Minasian L, Thompson I. Phase III trial of selenium to prevent prostate cancer in men with high-grade prostatic intraepithelial neoplasia: SWOG- S9917. Cancer Prev Res, 4:1761-96, 2011). Elizabeth Jacobs, Ph.D.: Associate Professor, Epidemiology, Univ. Arizona Cancer Center. (Jacobs ET, Giuliano AR, Roe DJ, Guillen-Rodriguez JM, Alberts DS, Martinez ME. Baseline dietary fiber intake and colorectal adenoma recurrence in the Wheat Bran Fiber Randomized Trial. J Natl Cancer Inst 94:1620-5, 2002). Cyndi Thomson, Ph.D., R.D.: Professor, Public Health, Health Promotion Sciences, Director, Univ. Arizona Canyon Ranch Center for Prevention & Health Promotion, Univ. Arizona Cancer Center. (Thomson CA, Giuliano AR, Shaw JW, Rock CL, Ritenbaugh CK, Hakim IA, Hollenbach KA, Alberts DS, Pierce JP. Diet and biomarkers of oxidative damage in women previously treated for breast cancer. Nutr Cancer 51(2):146-54, 2005). Elena Martinez, Ph.D.: Professor of Family & Preventive Medicine, Moores Cancer Center, Univ. California-San Diego. (Martinez ME, O'Brien TG, Fultz KE, Babbar N, Yerushalmi H, Qu N, Guo Y, Boorman D, Einspahr J, Alberts DS, Gerner EW. Pronounced reduction in adenoma recurrence associated with aspirin use and a polymorphism in the ornithine decarboxylase gene. Proc Natl Acad Sci U S A 100:7859-64, 2003). Patricia Thompson, Ph.D.: Associate Professor and Leader of Cancer Prevention and Control, University of Arizona Cancer Center. (Thompson PA, Wertheim BC, Roe DJ, Ashbeck EL, Jacobs ET, Lance P, Martinez ME, Alberts DS. Gender modifies the effect of ursodeoxycholic acid in a randomized controlled trial in colorectal adenoma patients. Cancer Prev Res 2(12):1023-30, 2009). Janine G. Einspahr, Ph.D., M.S.: Associate Professor, Department of Medicine, Univ. of Arizona Cancer Center. (Einspahr, JG, Calvert V, Alberts DS, Curiel-Lewandrowski C, Warneke J, Krouse R, Stratton SP, Liotta L, Longo C, Pellacani G, Prasad A, Sagerman P, Bermudez Y, Deng J, Bowden GT, Petricoin EF. Functional protein pathway activation mapping of the progression of normal skin to squamous cell carcinoma. Cancer Prev Res, 5:403-13, 2012). Clara Curiel, M.D.: Associate Professor and Director of Cutaneous Oncology, University of Arizona Cancer Center. (Curiel-Lewandrowski C, Swetter SM, Einspahr JG, Hsu C-H, Nagle R, Sagerman P, Tangrea J, Parnes H, Alberts DS, Chow H-H. Randomized, double-blind, placebo-controlled trial of sulindac in individuals at risk for melanoma: evaluation of potential chemopreventive activity. Cancer, 118: 2; 5848-5856, 2012). Joanne Jeter, M.D.: Associate Professor of Clinical Medicine, Univ. of Arizona Cancer Center. (Difluoromethylornithine: The Proof is in the Polyamines. Can Prev Res, 5:1341-1344, 2012). There is an old saying in academic medicine, “you are only as good as your last grant!” I began my academic career as an hematologic oncologist in 1967, focused on drug development for adult acute leukemia. By 1977, I was evolving into a medical gynecologic oncologist focused on drug development for advanced ovarian cancer (e.g. phase 1, 2 and 3 FDA approval trials of carboplatin and phase 2 and 3 trials of intraperitoneal cisplatin), and initiated and Chaired the Gynecologic Cancer Committee in the Southwest Oncology Group (1977-2002). A decade later, in 1989, I was asked by the Director of our University of Arizona Cancer Center (UACC) to develop a Cancer Prevention and Control Program to qualify the UACC for Comprehensive Status. So, in one day I was transformed from the Program Leader in Therapeutic Development to the Leader of Cancer Prevention and Control research. It was the best career move I ever made and led me to develop and Chair the Cancer Prevention and Control Program in the Gynecologic Oncology Group (and now, NRG) in 1994. Thus, GOG-199 (BSO vs. CA-125 surveillance in women at high risk for ovarian cancer), GOG-214 (Levonorgestrel vs. placebo to reduce the risk of ovarian cancer), GOG-225 (Diet and physical activity to reduce the recurrence of ovarian cancer in women in remission after surgery and chemotherapy) and NRG/GOG-002 (salpingectomy for women at high risk for ovarian cancer) were developed as cancer prevention trials in the GOG/NRG. So LESSON #4: Be willing to re-invent yourself, academically, every 10 years, or become a relic. And, what am I doing for an encore? I have not retired! I continue to serve as contact PI on our Native American Cancer Prevention U54 grant, serve as the PI on a R25T Cancer Prevention and Control training grant (a mechanism, sadly being discontinued by NCI), continue as PI for a NCI-funded “Chemoprevention of Skin Cancer Program Project,” am Co-PI on the DCI-DCP-funded UACC Phase 1/2 Chemoprevention Consortium and am the Co-Chair of the Cancer Prevention and Control Committee in the recently merged NRG/Gynecologic Oncology Group. In relation to these efforts, I find myself as the Co-PI on a 1,070 participant phase 3 trial, “Can Diet and Physical Activity Modulate Ovarian, Fallopian Tube and Primary Peritoneal Cancer Progression-Free Survival? (NRG/GOG-0225).” Dr. Cyndi Thomson is my Co-PI, once again emphasizing, “who is the Mentor and who is the Mentee?” But, it really doesn't matter, as long as we keep the field of cancer prevention and control alive, relevant, and vibrant! Citation Format: David S. Alberts. A funny thing happened to me while trying to cure ovarian cancer; I became a cancer prevention research specialist. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr PP01-01.