Randall F. Holcombe, MD, MBA

Randall F. Holcombe, MD, MBA

For all patient related matters:  Phone: (808) 586-5854 | Fax: (808) 586-5857
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Director, University of Hawaiʻi Cancer Center
Full Member, Cancer Biology Program, University of Hawaiʻi Cancer Center
Full Member, Populations Sciences Program, University of Hawaiʻi Cancer Center

Academic Appointment(s):
Professor (Researcher), University of Hawaiʻi Cancer Center
Professor of Medicine (Tenured), John A. Burns School of Medicine, University of Hawaiʻi at Mānoa

Degree(s):
MD, University of Medicine and Dentistry of NJ-New Jersey Medical School, Newark, NJ (1983)
MBA, Mount Sinai/Zicklin School of Business of Baruch College, New York, NY (2014)
Resident Physician, Internal Medicine, Brigham & Women's Hospital, Boston, MA (1983-1986)
Research/Clinical Fellow in Medicine (Hematology/Oncology), Brigham & Women's Hospital; Research Fellow in Genetics, Harvard Medical School, Boston, MA (1986-1989)

Personal Statement

As University of Hawaiʻi Cancer Center Director, I oversee all research activities and direct operational activities of the center, including allocation of space, appointment of faculty, and management of budgets and finances. I serve as the principal investigator for the P30 Cancer Center Support Grant and lead strategic planning initiatives as they relate to the Cancer Center.

Research Focus

1. Health services research in oncology
Quality-focused research has included description of a novel compensation model for clinical oncologists, development of a new tool to monitor adherence to evidence-based guidelines and proposal of new paradigm for consideration of healthcare quality. Additional research studies have focused on patient-reported outcomes, and specifically on the influence of demographic and structural factors that non-variably affect patient satisfaction scores, a critical element in value-based reimbursement models. These studies advance the field of health services research both for oncology and for healthcare overall.

2. Wnt signaling in colon cancer
We were the first to describe the selective expression of LEF1 in colon cancer and more recently described a novel Wnt-dependent pathway that controls the distribution of specific TCF isoforms. We have also identified a novel Wnt-stimulating ligand, Norrin that may control angiogenesis in the colon tumor microenvironment. These studies have advanced the understanding of Wnt signaling as a highly regulated signaling pathway that not only promotes carcinogenesis but also influences tumor invasion and metastases.

3. Role and mechanisms of action of natural products for cancer treatment and prevention
Laboratory studies demonstrated that resveratrol suppresses Wnt signaling in vitro. This led to a clinical trial of resveratrol, a dietary study of grape consumption that demonstrated that the primary effects were on normal mucosa, suggesting that the principal effectiveness may be in cancer prevention, rather than cancer treatment. Biological endpoints confirmed the activity of a resveratrol-containing whole food modulates Wnt signaling in patients, particularly those at increased risk for the development of colon cancer. This line of investigation has significantly contributed to our understanding of the role of natural products for cancer treatment and prevention, particularly with respect to their suppressive activity on Wnt signaling.

Selected Publications

Hashim D, Manczuk M, Holcombe R, Lucchini R, Boffetta P. (2016). Cancer mortality disparities among New York City's Upper Manhattan neighborhoods. Eur J Cancer Prevention, [epub ahead of print April 21].

Axelrad J, Kriplani A, Ozbek U, Harpaz N, Colombel JF, Itzkowitz S, Holcombe RF, Ang C. (2016). Chemotherapy tolerance and oncologic outcomes in patients with colorectal cancer with and without inflammatory bowel disease. Clin Colorectal Cancer, {epub ahead of print September 20. Pili: S1533-0028(16)30179-7. Doi: 10.1016/j.clcc.2016.09.005].

Holcombe RF, Evangelista M, Cartwright F. (2016). Delivering quality oncology care in a large, urban practice: A primer. J Oncology Practice, [epub ahead of print September 6. Pli:JOPR015040].

Uzilov AV, Ding W, Fink MY, Antipin Y, Brohl AS, Davis C, Lau CY, Pandya C, Shah H, Kasai Y, Powell J, Micchelli M, Castellanos R, Zhang Z, Linderman M, Kinoshita Y, Zweig M, Raustad K, Cheung K, Castillo D, Wooten M, Bourzgui I, Newman LC, Deikus G, Mathew B, Glicksberg BS, Moe AS, Liao J, Dudley JT, Maki RG, Kasarskis A, Holcombe RF, Mahajan M, Edelmann L, Hao K, Reva B, Longtine J, Starcevic D, Sebra R, Donovan MJ, Li S, Schadt EE, Chen R.(2016). Development and clinical application of an integrative genomic approach to personalized cancer therapy. Genome Medicine, 8:62 [doi: 10.1186/213073-016-0313-0].

Hingorani SR, Harris WP, Beck JT, Berdov BA, Wagner SA, Pshevlotsky EM, Tjulandin SA, Gladkov OA, Holcombe RF, Korn R, Raghunand N, Dychter S, Jiang P, Shepard HM, Devoe CE. (2016). Phase 1b study of PEGylated recombinant human hyaluronidase and gemcitabine in patients with advanced pancreatic cancer. Clinical Cancer Res, 22:2848-2854. [epub ahead of print 2016 Jan 26 pii: clincanres.2010.2015. PMID: 26813359 [HIGH ENROLLING INVESTIGATOR.]

Publication list via PubMed

Active Grants

R. Holcombe, PI (40%); CTO Interim Director (10%)
NCI
4P30CA071789-17
"University of Hawaii Cancer Center CCSG"
7/1/1996-6/30/2018
I assumed the position as University of Hawaiʻi Cancer Center Director in October, 2016.

Submitted/Planned Grants

MDSCs in chronic intestinal inflammatory disorders (co-I); NIH

Stimulatory role of IKKalpha in MDSC expansion and chronic intestinal inflammation (co-I); Crohn's & Colitis Foundation of America

Molecular basis of chronic inflammation-associated tumorigenesis (Co-I); NIH

Promotive effects of DNA-PKcs on MDSC expansion in chronic intestinal inflammation (co-I); Department of Defense

Macular pigment optical density as a surrogate measure of chemotherapy-associated cognitive impairment (PI); NCI PAR-16-213; 4/11/2017

Validation of a patient-reported outcomes instrument to measure cancer care coordination and address cancer health disparities (PI); NCI PAR-16-260; 6/5/2017

The cancer diagnosis as a teachable moment for lifestyle modification for Native Hawaiian families (PI); NCI PAR-14-260; 5/12/2017