Solid Tumor Therapeutics
The Solid Tumor Therapeutics Research Program focuses on the following disease groups: gastrointestinal cancers (esophageal, gastric, small intestine, colorectal, anal, hepatobiliary and pancreatic); genitourinary cancers (kidney, bladder, prostate, testicular); thoracic cancers (lung, mesothelioma), pediatric cancers, sarcoma, melanoma and head and neck cancers.
Given the diversity of disease sites represented by the program, as most solid tumors share (1) common alterations in the major signaling pathways regulating development and homeostasis, including the EGF, TGF-b, PDGF, VEGF, IGF, Hh, Wnt, Src and c-Met pathways, (2) conserved roles for the tumor microenvironment (immune system, angiogenesis), and (3) a need for more relevant pre-clinical or concurrent models, the program focuses on aligning the research efforts across these disease sites along these themes, promoting synergy across research groups at Duke and increasing disease specific drug development and testing with investigator initiated trials.
Specific Goals of the Program:
Promote synergy across the solid tumor research groups at Duke through a) regular meetings of the individual solid tumor research groups, b) quarterly thematic meetings of the signal transduction, tumor microenvironment and preclinical modeling focus groups and c) an annual retreat of the entire program membership.
Increase disease specific drug development with investigator initiated trials, including Phase I experimental therapeutics by a) promoting interactions with members of the Developmental Therapeutics Program to capitalize on their early stage drug discovery and lead development efforts b) providing support and infrastructure for clinical trials and c) leveraging the support of the NCI Experimental Therapeutics Clinical Trials Network with Phase I emphasis (ET-CTN) and National Clinical Trials Network (NCTN) lead academic site grants, both of which are housed in this program.
- Signal Transduction Pathways/Targeted Therapy Focus Group
- Tumor Microenvironment/Immunotherapy Focus Group
- Preclinical Modeling/Parallel Clinical Trials in Animal Models Focus Group
The Solid Tumor Therapeutics Program is led by Scott Antonia, MD, PhD, Jeffrey Crawford, MD, and Daniel George, MD. It is partitioned into three focus groups: Signal Transduction Pathways, led by Gerald Blobe, MD, PhD; Tumor Microenvironment/Immunotherapy, led by Smita Nair, PhD, and Preclinical Modeling, led by David Hsu, MD, PhD, and David Kirsch, MD, PhD.
Dr. Antonia is a medical oncologist within the thoracic oncology program and an immunobiologist who leads the DCI Center for Cancer Immunotherapy. Before joining Duke, Antonia was on the faculty at the Moffitt Cancer Center, where he served as Chair of the Thoracic Oncology Department and co-leader of the Moffitt CCSG Immunology Program. He has conducted several investigator-initiated clinical trials based on findings from his own research laboratory, as well as other basic science research collaborators, and recently published results of practice-changing clinical trials involving immune checkpoint inhibitors in lung cancer. He is currently working to identify basic research findings made by Duke investigators that are translatable as immunotherapeutic strategies, and forming multidisciplinary teams to test these in clinical trials across multiple cancer types.
Dr. Crawford is a co-leader of the Solid Tumor Therapeutics Program and the George Barth Geller Professor for Research in Cancer and served as chief of the Division of Medical Oncology for more than 10 years. He is vice-chair of the respiratory committee of the Alliance and site PI for DCI's participation, as well as lead PI for DCI as a lead academic site for NCTN. Dr. Crawford has championed clinical research, particularly the use of hematopoietic growth factors and new agents in lung cancer, including being national PI for the trials leading to the approval of G-CSF (filgrastim) in chemotherapy related neutropenia, and for vinorelbine in lung cancer. His current research includes serving as PI for 2 phase III trials of selective androgen receptor modulators in the prevention and treatment of sarcopenia in lung cancer patients receiving chemotherapy.
Dr Daniel George is Professor of Medicine and Surgery, Divisions of Medical Oncology and Urology in the Duke University School of Medicine. He also has appointments in the Duke Clinical Research Institute and the Duke Cancer Institute where he is the Director of Genitourinary (GU) Oncology. He is an internationally recognized clinical researcher and thought leader in GU malignancies, with over 150 peer-reviewed publications. His areas of research include new drug development and biomarkers of GU cancers with an emphasis on signal transduction pathways and angiogenesis. Dr. George has led the Duke site for the Department of Defense (DOD) Prostate Cancer Clinical Trials Consortium since 2006, specializing in Phase I and II studies in prostate cancer. He is also the PI of the MaRCC registry in advanced renal cell carcinoma and Co-PI of IRONMAN, an international, multi-sponsor supported registry in advanced prostate cancer. Dr. George serves on the ASCO scientific committee for non-prostate cancer, the Alliance GU scientific committee, NCI GU Steering Committee and the NCI Renal Task Force. He is co-leader of the DCI Prostate and Urologic Cancer Center.
Focus Group Leaders
Dr. Blobe leads the Signal Transduction Pathways Focus Group. He is a professor of medicine, pharmacology and cancer biology and has an active NCI-funded lab that studies TGF-b superfamily signaling, which has published over 90 papers in the field of cancer biology. He has served on NIH study sections as well as editorial boards.
Dr. Nair is leader of the Tumor Microenvironment/Immunotherapy Focus Group and an Associate Professor of Surgery. Her laboratory was instrumental in developing the RNA-transfected dendritic cell-based vaccination immunotherapy approach, and is currently focused on generating sustained effector and memory T cell immune responses that will translate to a therapeutic benefit for cancer patients. Dr. Nair has also helped establish the first GMP-production facility for dendritic cell-based cancer vaccines for Phase I clinical trials at DCI.
Doctors Hsu and Kirsch are co-leaders of the Preclinical Modeling/Parallel Clinical Trials in Animal Models Focus Group.
Dr. Hsu is the William Dalton Family Assistant Professor in Cancer Genomics. His laboratory focuses on the application of high-throughput technologies to match the individual patient with the most optimal therapy to improve clinical outcomes in patients with metastatic colorectal cancer. Along these lines, Dr. Hsu has been active in developing preclinical in vivo murine models to study new and novel therapeutic combinations, including patient derived human tumor xenografts.
Dr. Kirsch is a professor of radiation oncology, pharmacology and cancer biology, who has an active NCI-funded lab that studies sarcomogenesis and radiation biology using state of the art genetically engineered mouse models.
Dr. Gerry Blobe working with Dr. Andy Nixon in the Developmental Therapeutics Program, interrogated the tumor microenvironment of the pediatric tumor, neuroblastoma, to identify heparin sulfate proteoglycans as endogenous differntiating factors and modified heparins as potential differentiating therapies for these patients.
- Knelson, EH, Gaviglio, AL, Nee, JC, Starr, MD, Nixon, AB, Marcus, SG, and Blobe, GC. "Stromal heparan sulfate differentiates neuroblasts to suppress neuroblastoma growth." The Journal of Clinical Investigation 124, no. 7 (July 2014): 3016-3031. (Collaboration with Developmental Therapeutics)
- Supported by R01-CA136786 and Alex’s Lemonade Stand Reach and Innovation Award
Dr. Corinne Linardic working with Dr. Ashley Chi in the Cancer Genetic and Genomics Program, identify repression of the Hippo pathway as a mechanism of function of the PAX3-FOXO1 fusion protein in the pathogenesis of the pediatric cancer, alveolar rhabdomyosarcoma.
- Crose, LE, Galindo, KA, Kephart, JG, Chen, C, Fitamant, J, Bardeesy, N, Bentley, RC, Galindo, RL, Chi, JT, and Linardic, CM. "Alveolar rhabdomyosarcoma-associated PAX3-FOXO1 promotes tumorigenesis via Hippo pathway suppression." J Clin Invest 124, no. 1 (January 2014): 285-296.
- Supported by R01-CA122706
Drs. Neal Ready and Jeff Crawford, led a randomized, double-blind, placebo-controlled phase II study which suggests an advantage of chemotherapy with maintenance sunitinib for untreated extensive-stage small-cell lung cancer patients.
- Ready, NE, Pang, HH, Gu, L, Otterson, GA, Thomas, SP, Miller, AA, Baggstrom, M, Masters, GA, Graziano, SL, Crawford, J, Bogart, J, and Vokes, EE. "Chemotherapy With or Without Maintenance Sunitinib for Untreated Extensive-Stage Small-Cell Lung Cancer: A Randomized, Double-Blind, Placebo-Controlled Phase II Study-CALGB 30504 (Alliance)." Journal of Clinical Oncology : official journal of the American Society of Clinical Oncology 33, no. 15 (May 2015): 1660-1665.
Dr. Herbert Hurwitz, led a randomized, double-blind phase II study which supports a survival advantage of capecitabine with the JAK inhibitor, ruxolitinib , in second line metastatic pancreatic cancer patients.
Hurwitz, HI, Uppal, N, Wagner, SA, Bendell, JC, Beck, JT, Wade, SM, Nemunaitis, JJ, Stella, PJ, Pipas, JM, Wainberg, ZA, Manges, R, Garrett, WM, Hunter, DS, Clark, J, Leopold, L, Sandor, V, and Levy, RS. "Randomized, Double-Blind, Phase II Study of Ruxolitinib or Placebo in Combination With Capecitabine in Patients With Metastatic Pancreatic Cancer for Whom Therapy With Gemcitabine Has Failed." Journal of Clinical Oncology: official journal of the American Society of Clinical Oncology 33, no. 34 (December 2015): 4039-4047.
DCI Research Programs
Make A Gift
DONATE to support breakthrough research in solid tumor therapeutics at Duke.