John Goldberg, M.D.
Assistant Professor of Pediatrics
Description of Research
Dr. Goldberg's research focuses on the translation of laboratory discoveries into therapies for pediatric cancer and for cancers that overlap between adults and adolescents. This work has two main clinical thrusts: One is to develop targeted treatments for blood cancers based on work from laboratories here in Miami. The other is to develop immunotherapy based on work from the Dodson Interdisciplinary Immunotherapy Institute, including a DC vaccine program, and to explore the role of myeloid derived suppressor cells (MDSCs) in children with cancer.
Dr. Goldberg's programmatic goal is to continue to develop a Phase I pediatric cancer clinical trials organization within the University of Miami Sylvester Comprehensive Cancer Center, and to provide leadership to nascent efforts accross Florida to link pediatric cancer centers in a state-wide clinical trials group. In addition to the emphasis on Florida based developmental therapeutics, Dr. Goldberg is collaborating with HGG Immuno, based in Belgium, to develop the DC vaccines for brain tumors and sarcoma.
While at the Dana-Farber Cancer Institute, Dr. Goldberg led a vaccine protocol and a c-Met inhibitor protocol in patients with unusual sarcomas based on transcription factor biology. The c-Met inhibitor trial was opened at UM/Sylvester to treat both adults and children with these unusual cancers. He seeks to take his therapeutic ideas into the clinic through UM, and to bring these ideas to the national groups to make his novel ideas available to children everywhere. Conversely, because of group membership, he gains access for the children of Florida to more novel treatments from investigators accross the world.
In hematological malignancies, Dr. Goldberg is the national chair of a new protocol through TACL studying panobinostat. Similarly, he is designing two AMP kinase activator trials in relapsed pediatric acute lymphoblastic leukemia through the Sunshine Project. The first trial of AMP kinase activation involves the use of metformin in conjuction with chemotherapy. All of these protocols are based on work from Dr. Barredo's laboratory. Panobinostat is a novel HDAC inhibitor, more potent than currently approved HDAC inhibitors; and this class of compounds was found to be synergistic with chemotherapy against ALL. By speeding its development in the pediatric setting, he takes advantage of these findings to get the compound earlier for children who desperately need new treatments. AMP kinase is a regulator of cellular metabolism, and it is central to many processes within the leukemia cells that can be targeted with synergistic agents as well.
In solid tumors, he has grant funding to study DC vaccines in patients with recurrent high grade glioma (brain tumors) as well as to study DC vaccines in conjunction with standard chemotherapy in patients with relapsed sarcoma. The DC vaccine technique is based on science first described in murine systems by UM’s Eli Gilboa. Dr. Gilboa removed PGE2 from the maturation cocktail of the DCs and found that by substituting topical imiquimod treatment for PGE2, DC were mature but less tolerogenic. His Belgian collaborator, Stefaan Van Gool, took this technique into the clinic with remarkable results in brain tumor patients. He is now pursuing an international study of the DC technique, with other new advances from the Dodson mixed into the program. The sarcoma project represents a state wide collaboration adding gemcitabine to the Van Gool method of vaccination. The gemcitabine may act to suppress MDSCs and improve T cell responsiveness to the DC vaccine. Dr. Goldberg has a collaboration with the Diaz-Montero laboratory and the Division of Pediatric Clinical Research to study MDSCs in children. If these cells are elevated in pediatric cancer patients, they may be a predictive biomarker of response to therapy as well as a potential target for new immunotherapy based treatments.
- Initiated and oversaw Phase I clinical trial of vaccine in pediatric and adult patients in Boston
- Lead investigator and initiating investigator for ARQ 197-204, clinical trial of novel c-Met inhibitor in the MiT tumor patients
- SARC / TACL / Sunshine Project / HGG Immuno PI at the University of Miami
- Director, Pediatric Oncology Early Phase Clinical Trials Program at UM/Sylvester Comprehensive Cancer Center
Selected Cancer-Related Publications
Collaborating in the Multidisciplinary Research Program(s):