David Alberts

Dr. David Alberts
Regents Professor
University of Arizona
Arizona Cancer Center

After training at the NCI serving on the faculty and at the University of California, San Francisco, he moved in 1975 from UCSF to the University of Arizona Cancer Center, where he served as Director of the Cancer Prevention and Control Program from 1989 to 2005. The hallmark of his research career has been to take promising anticancer and chemopreventive agents, such as a -difluoromethylornithine (DFMO), ursodeoxycholic acid, selenium and sulindac sulfone from basic studies of their pharmacology all the way to the clinic. He has been continuously funded as PI of Program Project grants in colon (CCPPP) and skin cancer prevention since the 1980's.

Current Research: 

Four areas of his research are:

1. Retinoids in cancer treatment and prevention. Dr. Alberts' group has conducted landmark basic and clinical studies of retinoids (References #'s 65, 79, 94, 124, 129, 130, 163, 168). In a 2,297 patient trial (# 293), they reported that retinol is effective in preventing squamous cell skin cancer. Dr. Alberts helped demonstrate that topically applied all-trans-retinoic acid leads to regression of cervical intraepithelial neoplasia III (moderate dysplasia) (#'s 84, 135, 242). In a recent dose-finding trial of oral Vitamin A in participants with sun-damaged skin, he reported both efficacy and mechanism of action (# 399).

2. Biomarkers of skin carcinogenesis. Dr. Alberts helped to develop a panel of biomarkers for skin carcinogenesis, including proliferating cell nuclear antigen (PCNA), p53, polyamine levels and apoptosis (#'s 290, 324, 359). The biomarkers have been key to subsequent therapeutic trials, such as the demonstration that topical DFMO can prevent formation of actinic keratoses and reverse sun-related DNA damage (# 340). Dr. Alberts' group has developed topically administered chemopreventive agents that can be incorporated into sunscreens (#s 340, 362, 370). In a recent collaboration with Dr. Jeffrey Trent and others, reported in Nature (# 334), gene expression profiles were used develop a novel and clinically relevant taxonomy of malignant melanomas. Dr. Alberts' group has established VEGFR expression in pigmented moles as a biomarker that can differentiate dysplastic from benign nevi (# 434).

3. Prevention of colon cancer. Dr. Alberts has been a pioneer in the use of adenoma recurrence as a surrogate endpoint for preventing colon cancer in large population-based studies. Phase I and II studies of wheat bran fiber (WBF) preceded his negative phase III randomized study of WBF dietary supplementation (#'s 190, 184, 254, 261, 267, 271, 285, 287). The final results of a phase III randomized study of ursodeoxycholic acid (UDCA) for preventing adenoma recurrence in 1,285 randomized participants followed for three years after initial polypectomy revealed a 39% reduction in the recurrence of highly dysplastic polyps (i.e., the ones most likely to advance to invasive colorectal cancers) (#s 301, 420). The rationale for this study came partly from a phase I study demonstrating that UDCA could “washout” deoxycholic acid in fecal water (# 402). Enrollment began in 2002 for a phase III study of celecoxib and selenium, individually and together, to prevent adenoma recurrence in 1,600 patients. Previously, Dr. Alberts helped to oversee the Arizona Cancer Center phase III trial of selenium in 1,302 resected non-melanoma skin cancer patients. A secondary analysis of this trial documented a selenium-associated 56% reduction in risk of colon cancer incidence and a nearly 70% reduction in prostate cancer risk, which led to the 32,000 male SELECT phase III trial (# 278).

In another secondary analysis, a higher intake of Ca 2+ reduced by 45% the rate of adenoma recurrence in the WBF study (# 360). High-dose WBF supplementation failed to reduce secondary bile acid levels in fecal water in patients with resected colon adenomas; this finding may underlie the relative inactivity of WBF as a polyp prevention agent (# 372). A secondary analysis of the WBF trial data in combination with the NCI's high fiber vegetables and fruit phase III polyp prevention trial suggests that male polyp patients (but not female) may benefit from a high fiber diet to prevent polyp recurrence (# 5). Clinically vital new information concerning characteristics of incident adenomas that predict recurrence was also reported ( #s 318, 346).

4. Nuclear karyometric analysis as a biomarker of early neoplasia. In a series of recent papers published in collaboration with Dr. Peter Bartels in the Optical Science Center at the University of Arizona, Dr. Alberts has reported that subtle karyometric features of nuclear chromatin texture and spatial distribution denote very early neoplastic changes in skin, endometrium, ovary, cervix, colon, bladder and breast (#s 299, 352, 344, 347, 392, 357, 364, 380, 392, 393, 398, 408, 410, 421, 425). These statistically significant findings are of potentially great importance because they arise when the early neoplastic and normal cells are otherwise completely indistinguishable by all conventional histological criteria. The nuclear karyometric approach is beginning to have a major impact on identification of individuals at high risk for cancer and as a sensitive biomarker of response to chemopreventive agents (#s 393, 398).