- PROFESSOR Medicine, Hematology and Medical Oncology
American Board of Internal Medicine
MD, UMDNJ - University Hospital
Residency, Internal Medicine
Brigham and Women's Hospital, Harvard Medical School
Fellowship, Hematology & Onc.
Brigham and Women's Hospital, Harvard Medical School
- Randall F. Holcombe, MD is Chief Medical Officer, Cancer, Mount Sinai Health System; Professor of Medicine, Division of Hematology and Medical Oncology and Director of Clinical Cancer Affairs for Mount Sinai Medical Center. He has extensive experience in the conduct of clinical trials and is involved directly in clinical care and research for patients with colorectal cancer and other GI malignancies. Dr. Holcombe also serves as Director of the Ruttenberg Treatment Center at Mt. Sinai Hospital, Director of GI Medical Oncology and Deputy Director for the Tisch Cancer Institute. A leading authority in colon cancer, Dr. Holcombe has broad experience ranging from basic science and translational research to clinical trials and patient care. His research initially focused on levamisole, an adjuvant treatment for people with stage III colon cancer, which led to a national clinical trial. His focus since 1997 has been on the signaling of a protein called Wnt and its role in colon cancer development and progression. He has served as the principal investigator on 141 clinical trials, and led the team that was the first to describe the selective expression of the LEF1 gene in colon cancer. His laboratory has been examining the clinical effects of a naturally-derived compound called resveratrol on the prevention or treatment of colon cancer. He is deeply involved in the promotion and facilitation of translational and clinical research. More recently, Dr. Holcombe has been involved in health services and quality focused cancer research. His research has been funded by the NIH and multiple foundations and has resulted in more than 100 peer-reviewed manuscript publications and more than 170 published conference abstracts.
In the News
Dr. Holcombe discusses treatment of colon cancer in The Daily News feature The Daily Check Up.
Best Doctors in America: 2005-2010; 2011-2015
Dr Holcombe's Research Interests
1. Colon cancer prevention: Colon cancer is the third leading cause of cancer death for both men and women in the United States. Preventing this disease through the development of novel agents, many of them derived from naturally occurring compounds, is an area of specific interest. These compounds are undergoing testing both in the laboratory and in pilot clinical trials.
2. Wnt Signaling in Cancer: The Wnt signal transduction pathway is critical for the development and progression of many cancers but colon cancer in particular. Laboratory research is ongoing which will define the role of specific components of the Wnt signaling pathway in colon cancer and define mechanisms by which activation of this pathway contributes to a malignant phenotype. These studies are performed with an eye toward the development of new diagnostic tests, validation of new prognostic markers, and implementation and testing of novel targeted therapeutic interventions.
3. Clinical and Translational Research: Dr. Holcombe’s major focus has been on the development of hypothesis-driven, investigator-initiated trials in the area of gastrointestinal malignancies. Currently, Dr. Holcombe has several clinical trials in development for the treatment of patients with colon cancer and other gastrointestinal malignancies.
4. Health Services and Healthcare Quality: Transitioning oncology care to value-based paradigms is essential and an area of research focus over the past several years. Dr. Holcombe has published numerous manuscripts related to healthcare quality and novel models of care delivery.
Najdi R, Syed A, Arce L, Theisen H, Ting JH, Atcha F, Nguyen AV, Martinez M, Holcombe RF, Edwards RA, Marsh JL, Waterman ML. A Wnt kinase network alters nuclear localization of TCF-1 in colon cancer. Oncogene 2009 Nov; 28(47).
Nguyen AV, Albers CG, Holcombe RF. Differentiation of tubular and villous adenomas based on Wnt pathway-related gene expression profiles. International journal of molecular medicine 2010 Jul; 26(1).
Najdi R, Holcombe RF, Waterman ML. Wnt signaling and colon carcinogenesis: beyond APC. Journal of carcinogenesis 2011; 10.
Abou-Alfa GK, Chan SL, Lin CC, Chiorean EG, Holcombe RF, Mulcahy MF, Carter WD, Patel K, Wilson WR, Melink TJ, Gutheil JC, Tsao CJ. PR-104 plus sorafenib in patients with advanced hepatocellular carcinoma. Cancer chemotherapy and pharmacology 2011 Aug; 68(2).
Planutiene M, Planutis K, Holcombe RF. Lymphoid enhancer-binding factor 1, a representative of vertebrate-specific Lef1/Tcf1 sub-family, is a Wnt-beta-catenin pathway target gene in human endothelial cells which regulates matrix metalloproteinase-2 expression and promotes endothelial cell invasion. Vascular cell 2011; 3.
Martinez M, Ono N, Planutiene M, Planutis K, Nelson EL, Holcombe RF. Granulocyte-macrophage stimulating factor (GM-CSF) increases circulating dendritic cells but does not abrogate suppression of adaptive cellular immunity in patients with metastatic colorectal cancer receiving chemotherapy. Cancer cell international 2012; 12(1).
Dellinger TH, Planutis K, Jandial DD, Eskander RN, Martinez ME, Zi X, Monk BJ, Holcombe RF. Expression of the Wnt antagonist Dickkopf-3 is associated with prognostic clinicopathologic characteristics and impairs proliferation and invasion in endometrial cancer. Gynecologic oncology 2012 Aug; 126(2).
Galsky MD, Posner M, Holcombe RF, Lee KM, Misiukiewicz K, Tsao CK, Godbold J, Soto R, Gimpel-Tetra K, Lowe N, Oh WK. Phase Ib study of dovitinib in combination with gemcitabine plus cisplatin or gemcitabine plus carboplatin in patients with advanced solid tumors. Cancer chemotherapy and pharmacology 2014 Sep; 74(3).
Dellinger TH, Planutis K, Tewari KS, Holcombe RF. Role of canonical Wnt signaling in endometrial carcinogenesis. Expert review of anticancer therapy 2012 Jan; 12(1).
Pintova S, Sidhu H, Friedlander PA, Holcombe RF. Sweet's syndrome in a patient with metastatic melanoma after ipilimumab therapy. Melanoma research 2013 Dec; 23(6).
Planutis K, Planutiene M, Nguyen AV, Moyer MP, Holcombe RF. Invasive colon cancer, but not non-invasive adenomas induce a gradient effect of Wnt pathway receptor frizzled 1 (Fz1) expression in the tumor microenvironment. Journal of translational medicine 2013; 11.
Adelson KB, Qiu YC, Evangelista M, Spencer-Cisek P, Whipple C, Holcombe RF. Implementation of electronic chemotherapy ordering: an opportunity to improve evidence-based oncology care. Journal of oncology practice / American Society of Clinical Oncology 2014 Mar; 10(2).
Holcombe RF. Cancer clinical research: return on investment in the era of value-based purchasing. Journal of oncology practice / American Society of Clinical Oncology 2014 Sep; 10(5).
Planutis K, Planutiene M, Holcombe RF. A novel signaling pathway regulates colon cancer angiogenesis through Norrin. Scientific reports 2014; 4.
Alistar A, Sung M, Kim M, Holcombe RF. Clinical pathways for pancreatic neuroendocrine tumors. Journal of gastrointestinal cancer 2012 Dec; 43(4).
Iqbal S, Rankin C, Lenz HJ, Gold PJ, Ahmad SA, El-Khoueiry AB, Messino MJ, Holcombe RF, Blanke CD. A phase II trial of gemcitabine and capecitabine in patients with unresectable or metastatic gallbladder cancer or cholangiocarcinoma: Southwest Oncology Group study S0202. Cancer chemotherapy and pharmacology 2011 Dec; 68(6).
- A Phase 1 Study of Ly2801653 in Patients with Advanced Cancer
- A feasibility and adherence study of personalized therapeutic interventions targeting minimal residual disease following adjuvant colon cancer therapy
- Genistein Combined with FOLFOX or FOLFOX-Avastin for treatment of Metastatic Colorectal Cancer: Phase I/II Pilot Study
- A phase 2 randomized multicenter study of PEGPH20 (hyaluronidase) combined with nab-paclitaxel plus gemcitabine compared with nab-paclitaxel plus gemcitabine in subjects with stage IV previously untreated pancreatic cancer
Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.
Dr. Holcombe did not report having any of the following types of financial relationships with industry during 2014 and/or 2015: consulting, scientific advisory board, industry-sponsored lectures, service on Board of Directors, participation on industry-sponsored committees, equity ownership valued at greater than 5% of a publicly traded company or any value in a privately held company. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.
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