Translational researchers Drs. Dong M Shin & Fadlo R Khuri
Despite increases in the incidence of human malignancies, progress towards the treatment and prevention of cancers over the last two decades has been slow. However, recent advances in sophisticated imaging techniques, molecular oncology, and the development of targeted agents are potential accelerators towards more effective early diagnosis, detection and treatment of common tumor types. The extensive involvement of physician-scientists, who understand both the basic molecular mechanisms of disease and the clinical applications of such advances, can expedite the translation of molecular breakthroughs to the diagnosis of disease and the development of optimal treatments.
In 2009, Emory’s Winship Cancer Institute (Winship) became the first NCI-designated Cancer Center in the state of Georgia. The Department of Hematology and Medical Oncology (HMO) is a main component of the Winship, whose goal as a matrix cancer center is to create a “discovery accelerator” that enables the translation of science to patients and populations and the measurement of our impact. Thus, the HMO Department actively encourages new fundamental discoveries, investigator-initiated research and clinical trials, which are crucial to meeting our goals for reducing cancer morbidity and mortality. Examples of some of the translational research programs within the HMO Department include:
Lung and Aerodigestive Program: Developing molecular, prognostic, therapeutic, and chemopreventive approaches to improve standard of care in patients with tobacco-related cancers. The Lung P01 program, consisting of four major research projects, investigates the mechanism of action of signal transduction pathways and their inhibitors in lung cancers, and examines tumor samples for their methylation status of genes that may influence response rates to platinum-based and taxane-family drugs and other molecularly targeted agents. The Head and Neck Cancer SPORE is the only SPORE program at Emory University and the state of Georgia, and consists of four major research programs and supporting cores. The green tea clinical study uses a chemopreventive approach and combines green tea polyphenon E (PPE) and erlotinib to prevent carcinogenesis in patients with premalignant lesions of the head and neck. Other HN SPORE translational projects include the development of curcumin analogs, and the study of death receptors, nanotherapeutics, and cancer cell metabolism.
Genitourinary Research: Innovative research investigating new approaches to prostate, kidney and bladder cancer therapies using combinations of chemotherapy, radiation therapy and nutritional agents. Soy isoflavones in combination with standard therapy are currently under clinical investigation for prostate cancer.
Chemoprevention, Nutrition and Cancer: Preclinical and clinical translational research investigates the potential use of natural compounds, including green tea, lycopene, luteolin, resveratrol, soy isoflavones, honokiol, and curcumin analogs for the prevention and treatment of cancer. Lycopene and soy isoflavones are potent anti-cancer agents which may be useful in preventing and slowing the progression of prostate cancer in particular, and possibly preventing chemotherapy- and radiation therapy-induced toxicities. Furthermore, soy isoflavones may enhance the efficacy of chemotherapy in a variety of malignancies. Combinations of natural compounds with molecularly targeted agents (e.g., green tea PPE plus EGFR-TKI) are being explored.
The Translational Breast Cancer Research Program researches the use of hormonal and targeted therapies, and studies the mechanisms of selective estrogen receptor modulator (SERM) resistance and the evaluation of novel targeted approaches for triple negative breast cancer, which has led to the development of novel trials for patients with this subtype of breast cancer. Another goal of the breast cancer program is to understand the different genetic variations involved in cancer development and to devise targeted treatments based on those variations.
The Gastrointestinal Oncology Program focuses on targeted therapies for pancreatic, gastric and colorectal cancers. This program includes investigator-initiated phase I and II studies through NCI-initiated clinical consortiums.
The Leukemia Program focuses on the development of novel targeted agents for the treatment of patients with leukemia and myelodysplastic syndromes, and also studies dynamic genetic profile changes in cancer cells collected from patients with hematological malignancies throughout the course of their disease. The data collected are used to help physicians better tailor anti-cancer treatment modalities such as pathway-targeted therapies—immunotherapy using bone marrow transplantation to prevent relapse following standard chemotherapy. Other treatment approaches include targeted therapies using small molecules (tyrosine kinase inhibitors) for CML, monoclonal antibody therapy for AML, and biological therapies such as interferon-alfa for CML and all trans-retinoic acid (ATRA) for acute promyelocytic leukemia.
Lymphoma Research studies the molecular mechanisms that may contribute to the development of several lymphoid cancers such as multiple myeloma, non-Hodgkin's and Hodgkins lymphoma, and may represent possible pathways to deliver targeted therapies.
Myeloma: Cutting edge research using arsenic to induce apoptosis in myeloma. Arsenic trioxide is FDA-approved for the treatment of acute promyelocytic leukemia (APL), and is being tested in several other diseases including bone marrow cancers and multiple myeloma. Other myeloma research focuses on cancer immunotherapy with preclinical and clinical research focusing on dendritic cell function in the context of allo transplantation, and on developing a B-cell malignancy program with respect to novel targeted agents in laboratory models as well as early clinical trials.
BMT: Research to make bone marrow, peripheral blood stem cell and cord blood transplants safer and more effective. Recent advances include new combinations of chemotherapy that increase the likelihood of a successful transplant, so that transplants are safer and more feasible for a wider range of patients who could benefit from these procedures.
Cell Therapy: Immune reconstitution after high dose chemotherapy and hematopoietic progenitor cell transplantation represents a significant clinical problem, as patients with poor post-transplant immunity have increased opportunistic infections and increased risk for cancer recurrence. Translational research focuses on developing novel strategies to enhance immunity with a focus on the interaction between dendritic cells and T-cells. Additional research focuses on cell and gene therapy for cancer and immune ailments, regenerative medicine. Laboratory research is focused on cell and biological therapy for cancer and immune ailments, exploring the utility of stem cells for regenerative medicine, immune modulation, and delivery of therapeutic proteins for treatment of acquired and hereditary diseases.
Each of these organ site research programs is closely associated with the four main programs of the Winship Cancer Institute: Cancer Cell Biology (CCB), Cancer Prevention and Control (CPC), Cancer Genetics and Epigenetics (CGE), and Discovery and Developmental Therapeutics (DDT).