Atfi Lab Research
Molecular mechanisms of cancer and cancer-associated cachexia
Azeddine Atfi, PhD, is the Chair of the Cellular and Molecular Pathogenesis Division in the Department of Pathology at VCU. Dr. Atfi’s lab is interested in investigating the molecular mechanisms of malignant transformation that underlay human cancers, with particular emphasis on the role of the transcriptional repressor TGIF in osteosarcoma and pancreatic ductal adenocarcinoma progression (PDAC). Osteosarcoma is the second leading cause of cancer-related death in adolescents. In patients with metastatic or relapsed osteosarcoma, there is currently no reliable therapeutic option to provide long-term tumor control. PDAC is among the most lethal malignancies with a 5-year survival of less than 5%. Obstacles to improving patient outcome include a lack of clear understanding of disease pathogenesis and progression, poor early detection tools, the inherently aggressive behavior of the tumor leading to early metastasis, and a lack of effective chemotherapeutics. Combining an unbiased global insertional mutagenesis-based strategy with Tgif genetic deletion in vivo, Dr. Atfi’s lab has discovered that TGIF functions as a tumor suppressor in both osteosarcoma and PDAC. Using a variety of genetic and pharmacological approaches, Dr. Atfi’s team is currently investigating the molecular mechanisms by which TGIF restricts the progression of these highly aggressive malignancies. Besides osteosarcoma and PDAC, Dr. Atfi’s lab is also interested in studying cancer-driven muscle cachexia. Extensive epidemiological studies indicate that one in four of the general population will die from cancer, and cachexia affects the majority of patients with advanced malignancies. Sadly, few therapeutic options are currently available for preventing or even delaying cancer cachexia. Of particular relevance, recent studies performed in Dr. Atfi’s lab has yielded new insights into the mechanisms behind the muscle loss in cancer patients. Subsequent to these intriguing findings, Dr. Atfi’s lab initiated a translation research project that is aimed at developing clinical trials, with the ultimate goal to identify new opportunities for effective therapeutic interventions to curb muscle cachexia in cancer patients.