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Faculty

Randall F. Holcombe, MD, MBA

Randall F. Holcombe, MD, MBA
  • Director
    University of Hawaii Cancer Center
  • Full Member
    Cancer Biology Program
    University of Hawaii Cancer Center
  • Populations Sciences Program
    University of Hawaii Cancer Center
  • Academic Appointments

  • Professor (Researcher)
    University of Hawaii Cancer Center
  • Professor of Medicine (Tenured)
    John A. Burns School of Medicine
    University of Hawaii at Mānoa

Degree

  • M.D.
    University of Medicine and Dentistry of NJ-New Jersey Medical School
    Newark, NJ (1983)
  • M.B.A.
    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 Hawaii 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 related 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.]
  • McFarland DC, Shen M, Holcombe RF. (2016). Predictors of Patient Satisfaction with Inpatient Hospital Pain Management Across the United States: A National Study. J Hospital Medicine, [epub ahead of print, March 11, 2016; doi:10.1002/jhm.2576].
  • McFarland DC, Shen M, Holcombe RF. (2016).Predictors of Satisfaction with Doctor and Nurse Communication: A National Study. Health Communication, [epub ahead of print, September 9:1-8].
  • Hashim D, Farhat Z, Wallenstein S, Manczuk M, Holcombe RF, Thorpe L, Schymura M, Lucchini RG, Boffetta P. (2016). Standardized cancer incidences disparities in upper Manhattan New York neighborhoods: Role of race/ethnicity, socioeconomic status and known risk factors. Eur J Public Health, 25:349-356. [epub ahead of print, July 16, 2015]. [CLINICAL RELEVANCE COORDINATION.]
  • Planutis AK, Holcombe RF, Planoutene MV, Planoutis KS. (2015). SW480 colorectal cancer cells that naturally express Lgr5 are more sensitive to the most common chemotherapeutic agents than SW480 cells that do not express Lgr5; the difference in sensitivity between Lgr5-positive and Lgr5-negative cells is more pronounced with irinotecan than with oxaliplatin. Anti-Cancer Drugs, 90:942-947. [epub ahead of print, July 20, 2015]. [LABORATORY PI.]
  • Holcombe RF, Martinez M, Planutis K, Planutiene M. (2015). Effects of grape-supplemented diet on markers of proliferation and Wnt signaling in colonic mucosa: Implications for colon cancer prevention are greatest for individuals over age 50 and individuals with high consumption of dietary arginine. Nutrition Journal, 14:62. [doi: 10.1186/s12937-015-0050-z].
  • McFarland DC, Holcombe RF, Holland J. (2015). Inpatient hematology-oncology rotation is associated with a decreased interest in pursuing oncology career among internal medicine residents. J Oncology Practice,11:289-295. [epub 6/10/2015, doi: 10.1200/JOP.2015.003798] [With invited commentary].
  • McFarland DC, Ornstein K, Holcombe RF. (2015). Demographic Factors and Hospital Size Predict Patient Satisfaction Variance- Implications for Hospital Value-Based Purchasing. J Hosp Medicine,10:503-509. [epub 5/4/2015, doi:10.1002/jhm.2371].

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 Hawaii Cancer Center Director in October, 2016.
  • R. Holcombe, P:I (40%); CTO Interim Director (10%)
    NCI
    3P30CA071789-17S1 NCI
    "University of Hawaii Cancer Center CCSG"
    7/1/1996-6/30/2017
    I assumed the position as University of Hawaii Cancer Center Director in October, 2016.
  • R. Holcombe, PI (40%); CTO Interim Director (10%)
    NCI
    3P30CA071789-17S2 NCI
    "University of Hawaii Cancer Center CCSG"
    7/1/1996-6/30/2017
    I assumed the position as University of Hawaii Cancer Center Director in October, 2016.
  • R. Holcombe, PI initially, now ClI
    DSM Nutritional Products, Inc
    "Genistein Combined with FOLFOX or FOLFOX-Avastin for treatment of Metastatic Colorectal Cancer: Phase II Pilot Study"
    Support an investigator-initiated study under IND#: 19-396. Based at Mount Sinai, NY.
    7/1/2014-6/30/2017

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