Afshin Dowlati, MD
Director, Center for Cancer Drug Development and Deputy Associate Director for Clinical Research-Translational Researchaxd44@case.edu 216.844.1228 (o)
Director, Thoracic Oncology Program, University Hospitals Seidman Cancer Center
Professor, Division of Hematology and Oncology
Co-Leader, Developmental Therapeutics Program
Dr. Dowlati attended the University of Liege School of Medicine and after completing an internal medicine residency there in 1996, came to Case Western Reserve University School of Medicine for an internal medicine residency and a fellowship in hematology and oncology. He joined the Case Comprehensive Cancer Center in 2000 and became Co-Leader of the Developmental Therapeutics Program in 2007.
Dr. Dowlati’s lab is interested in the biology and clinical management of thoracic malignancies, with particular emphasis on translational aspects of drug development. Lung cancer has become the most frequent and lethal cancer worldwide. Non-small-cell lung cancer (NSCLC) histological types comprise about 85% of all lung cancer cases. Although recent advances in molecular targeting have discovered novel therapeutics for the treatment of NSCLC, including agents targeting the epidermal growth factor receptor (EGFR), these agents unfortunately work in only a small minority of lung cancer patients. Thus, most NSCLC is usually chemo-resistant and it remains critical to develop new therapeutic strategies. In this regard the transcription factor STAT3 demonstrates constitutive activation in lung cancer and blockade of STAT3 activity results in apoptosis and cell death in NSCLC cell lines. STAT3 regulates genes involved in cell cycle, apoptosis, angiogenesis, tumor invasion and metastasis. The location of STAT3 at the end of a signaling pathway makes it an attractive potential therapeutic target. To date, no effective STAT3 inhibitor has been found. Therefore, Dr. Dowlati’s team of researchers have looked to endogenous STAT3 inhibitors as potential areas for drug discovery and are focusing our efforts on a protein inhibitor of activated STAT3 (PIAS) called PIAS3.
Small cell lung cancer (SCLC) represents the remaining 15% of all lung carcinomas. SCLC is typically diagnosed after the disease has metastasized and resistance to ensuing chemotherapy rapidly develops, leading to low patient survival. Unlike NSCLC, molecular targeted agents have all failed to improve survival of SCLC patients. Dr. Dowlati hypothesizes that this failure of targeted therapy is due to a greater array of oncogenic mutations that drive SCLC growth and proliferation that remain largely undiscovered. Dr. Dowlati is using multiple technology platforms to identify these mutations with particular interest in identification of actionable mutations, i.e. where clinically-approved drugs are already available. These efforts will lead not only to a better understanding of the cancer biology of SCLC but more importantly will open a fast track to novel targeted therapies for this lethal disease.
small cell lung cancer, non-small-cell lung cancer, mesothelioma, squamous cell lung cancer, SCLC, NSCLC, tyrosine kinase receptors, STAT3, PIAS3