David S. Alberts, MD: In Memoriam (1939–2023)

With the death on July 29, 2023 of David Alberts, known far and wide as Dave, the cancer research community lost a true colossus. His interests over the years spanned the clinical pharmacology of anticancer drugs, the treatment of women's cancers, and cancer prevention. His contributions in each field garnered international recognition. At the same time, Dave mentored numerous individuals at every career stage, assumed multiple leadership roles at his own institution and beyond. Remarkably, he always remained a busy physician providing extraordinary care to countless patients.

Dave was born in Milwaukee on December 30, 1939, where first-cousin Bruce Alberts describes the cousins growing up in a large extended family. The death from cancer of another cousin, Reed, at the age of 20, provided the inspiration for Dave to become a cancer physician. After Shorewood High School in Milwaukee, he attended Trinity College, Hartford, CT, before obtaining his MD from the University of Virginia (Charlottesville, VA). After Medicine Internship at the University of Wisconsin, Madison (Madison, WI), he became a Clinical Associate in Pharmacology at NIH/NCI and then completed his Medicine Residency at the University of Minnesota (Minneapolis, MN). He then moved to the University of California, San Francisco (UCSF; San Francisco, CA) for further training in clinical pharmacology and medical oncology. On one illustrious rotation at UCSF, Dave was the oncology fellow, Frank Meyskens the resident, and Dan Von Hoff the intern; all three would later be Directors of NCI Cancer Centers. Dave remained on faculty at UCSF until recruited in 1975 by Sydney Salmon to the recently created University of Arizona Cancer Center (UACC; Tucson, AZ), his academic home for the rest of his career.

From a groundbreaking report of the pharmacokinetics of daunorubicin in humans while training at NCI and work on cytotoxic agents for the treatment of myeloma at UCSF, Dave quickly progressed to gain recognition for his work at UACC on the efficacy and clinical pharmacology of commonly used and investigational cytotoxic agents. Agents studied by Bob Dorr and others in the Alberts lab included bleomycin, chlorambucil, cisplatin, cyclophosphamide, and melphalan. Most of the agents first required de novo development of assays to measure tissue and body-fluid levels. During this period, Dave developed his interest in novel therapies for gynecologic cancers.

Dave's major contributions to improving gynecologic cancer outcomes derived from a combination of his scientific creativity and leadership roles in the Southwest Oncology Group, the Gynecologic Oncology Group, and other large groups that he steadily accrued. Setsuko Chambers comments that he was an early proponent in the 1980s of intraperitoneal chemotherapy for ovarian cancer, which later became a mainstay of treatment. He helped to lead early studies that established the benefits of maintenance therapy for patients with ovarian cancer, now the standard of care.

Dave managed to keep both individual and community/population in mind: he always thought holistically about the individual patient with cancer, all the while seeking to reduce society's overall cancer burden. He was in the vanguard in his steady determination to persuade the cancer research community to focus on preventive measures to reduce cancer morbidity and mortality as well as on therapeutic advances for advanced disease. He initiated studies of chemotherapy-related cognitive impairment in patients with ovarian cancer. In 1989, he became the inaugural Director of UACC's Cancer Prevention and Control Program, which he led to national prominence over the next 16 years.

Chemoprevention was considered a field of great promise in the 1980s and 1990s. Once again, Dave was an early leader in what was, for him, a new field of research. He chaired a key NCI committee on chemoprevention and started a colorectal cancer prevention program funded by NCI at UACC in the late 1980s; he led this for nearly two decades before handing over to one of us (P. Lance). The program endures, now under the leadership of Beth Jacobs. Three phase III randomized controlled chemoprevention trials in a combined total of over 4,000 patients were completed from 1990 to 2013. Using colorectal adenoma as a surrogate endpoint for colorectal cancer, the primary outcome in each trial was a comparison of the development of new/metachronous adenoma in patients receiving intervention versus placebo.

Although all three trials had null outcomes, thanks to Dave's trial design the material collected from participants—including a meticulously annotated biobank—is a rich resource for ancillary studies that has yielded over 90 publications to date. Topics include dietary and other lifestyle risk factors for colorectal adenoma; genome-wide association studies of metachronous adenoma risk; response to selenium supplementation; selenium supplementation and risk for type 2 diabetes; and modeling of incident adenoma characteristics to determine best-practice surveillance colonoscopy intervals.

Arizona has among the highest rates of skin cancer in the world; their prevention was a natural focus for Dave. In the 1980s and 1990s, he completed the first phase II randomized trial of isoretinoin for advanced head and neck squamous cell carcinoma (SCC) and led the retinoid skin cancer prevention (SKICAP) trial. These trials were pivotal in establishing the use of systemic retinoids as part of usual preventive care for transplant and other patients with severe skin photodamage or a history of multiple cutaneous SCC.

In the late 1990s, Dave started an NCI-funded Skin Cancer Prevention program with Tim Bowden, focusing on novel chemoprevention strategies. Melanotan-1 was developed and first brought to the clinic through the program and is now FDA approved for use in patients with porphyria. Painstaking dissection of the mechanistic roles of the MAPK and PI3K pathways in the development of cutaneous SCC was another important contribution. The program continues—Dave's legacy in action—under the leadership of Clara Curiel.

As an index of Dave's extramural support, when the journal Science “took a look at the people at the top of the funding heap” in 2001, Dave was one of the three “top-funded clinical, social science PIs” in the entire NIH portfolio. Now in its fourth edition, his book Fundamentals of Cancer Prevention (Heidelberg: Springer), co-edited with Lisa Hess, is testimony to his preeminence in the cancer prevention field.

Advising and mentoring activities were inextricably woven into Dave's research. He found time to supervise an astonishing number of masters and PhD students, postdoctoral fellows, and junior faculty. In assiduously supporting the career interests of women he was, as usual, ahead of his time. Many of those whom Dave advised early in their careers went on to leadership roles in academic organizations and industry, including two who became Directors of NCI Comprehensive Cancer Centers.

Three decades of dedication to the institution culminated in Dave's appointment as UACC Director from 2005 to 2013. During his tenure, the UACC Skin Cancer Institute was founded and major new clinic buildings were established in Tucson and Phoenix. He was proud and protective of UACC's role as the only NCI Cancer Center headquartered in Arizona and championed its mission to serve the whole state; as Director, he led a statewide NCI-supported partnership for cancer prevention with the Native American community.

Dave's prominence in the cancer research community-at-large reflected his accomplishments at home. He served on the External Advisory Committees of many of the country's largest NCI Cancer Centers and as a member of the NCI's Board of Scientific Advisors. He was Co-Editor-in-Chief of Cancer Epidemiology Biomarkers and Prevention with one of us (J. Potter) from 2003 to 2008. He was a joy to work with, thoughtful about the careers of young researchers, nurturing their output, always with an eye on opportunities to teach and mentor.

Among many honors, The University of Arizona (Tucson, AZ) awarded Dave its highest academic honor of Regents Professor. He received AACR's Eighth Annual H. Burchenal Clinical Research Award and the Second Annual Pioneer Award in Cancer Prevention as well as the 2004 American Society of Preventive Oncology's Joseph F. Fraumeni Jr Distinguished Achievement Award.

What an extraordinary combination of humility, passion, commitment, humanity, and wisdom we have lost in Dave Alberts! Janine Einspahr observes that he had a talent for pulling together exceptional groups of researchers for projects/grants. Jeff Trent tells us that Dave—suffering from Valley Fever, tied to IVs, and in his hospital gown—successfully defended a P01 project. His legacy includes many scientists who will continue the work of cancer prevention and cancer treatment, walking in Dave's footsteps and cutting new paths. At the beating heart of Dave's entire career was his role as a dedicated physician, practicing until the day he retired and sustaining his practice tirelessly during years of heavy administrative responsibilities. His commitment to his patients was unique and legendary; it included indiscriminately providing his cell-phone number. He was so available to so many!

One can only understand how Dave scaled the professional heights that he did by appreciating his irrepressible wife Heather of 60 years, their children Tim and Sabrina and their spouses, and Dave and Heather's five grandchildren. There was no boundary between Dave's professional and family lives—and Heather was omnipresent in Dave's professional life. Dave is truly irreplaceable.