The focus of the research in Dr. Munoz-Antonia's laboratory is to examine the prognostic and diagnostic value of the expression of transforming growth factor beta (TGFb) pathway molecules in human cancer. The pattern of alteration of critical proteins in early stages of tumor development may explain why cells that have the potential to transform into fully malignant tumors develop into tumors with low to moderate malignant potential. Dr. Mu'oz-Antonia and her colleagues have shown a direct correlation between resistance to the antiproliferative effects of TGFb, tumorigenicity, and decreased expression of TGFb type II receptor proteins. Their hypothesis is that dysregulated expression of signal transduction signaling components in epithelial cancers can be correlated with disease status. Their data on expression of the TGFb receptors and signaling proteins (Smads) in head and neck, thyroid, and lung tumors confirm this hypothesis. They have demonstrated a defect (either at the gene or protein level) in one of the components of the TGFb signaling pathway (receptors or Smads) in most primary tumors examined. Dr. Mu'oz-Antonia and her colleagues continue to test their hypothesis by examining the status of these molecular markers in the context of disease stage in different tumor types.
In collaboration with investigators from the University of Puerto Rico, Dr. Munoz-Antonia and her colleagues have found significant differences in the expression of some TFGb signaling components in squamous cell cancers of the head and neck of Puerto Rican Hispanics. Some of these differences, such as decreased expression of TGFb type I receptor, are independent of human papillomavirus status, while others, such as decreased expression of Smad4, correlate with the presence of human papillomavirus. The development of tumor-specific biomarkers that identify patients at risk of developing recurrence, metastasis, or a second primary tumor could be useful to develop individualized treatment strategies.