Adhesion signaling in hepatocellular carcinoma; RFA treatment of breast cancer

The Adams laboratory utilizes tools of cell biology, protein chemistry, molecular biology and whole animal models to understand how adhesion-signaling pathways control cell growth and apoptosis.  A specific understanding of these processes in prostate cancer initially, and more recently, hepatocellular carcinoma has been sought.  Aberrations of these processes in cancers and the resulting changes resulting in tumor growth, and treatment resistance is the focus of studies in the laboratory.  A major focus of this research is focal adhesion kinase (FAK) signaling, a principle regulatory component of cell adhesion, anchorage independent survival and the prevention of apoptosis.  In particular, its regulation in prostate, and hepatocellular carcinomas have been investigated.  Furthermore, the role of focal adhesion kinase on treatment resistance has been studied.  Recent findings have demonstrated the role of FAK in prostate cancer adhesion signaling and its constitutive activation in cancer cells.  Additional studies on human specimens have demonstrated its regulation in cancer versus normal prostate tissues.  Experimental studies of hepatocellular carcinoma on cell lines and human tumors demonstrate persistent (constitutive) FAK phosphorylation in these tumors.  Inhibition of phosphorylation results in apoptosis.  The laboratory has demonstrated for the first time that combination therapy with FAK inhibition and a cytotoxic agent (cisplatin) results in a high rate of apoptosis in hepatocellular carcinoma cells.  Animal studies demonstrate that this combination, unlike single agent therapy, prevents tumor growth in tumor xenografts.  This suggests a potential target and strategy for the treatment of this difficult tumor.  This research made use of the Biostatistics Core, to help evaluate treatment effects, the tissue procurement core for specimen retrieval and processing, the histology core for tissue processing and examination, and the vivarium for animal model experiments.
Clinical programs include a collaborative project aimed at understanding the treatment utility of radiofrequency ablation (RFA) in breast cancer.  This study seeks to determine targeting efficacy and treatment completeness.  An important component of this study is the pre and post treatment imaging of breast cancers treated by RFA.  Currently no studies have been done to determine the appropriate method of determining completeness of ablation.  This study hypothesizes that MRI will be the most efficacious at determining completeness of ablation.  Collaboration on this study involves radiology, pathology, surgery, and the Human Immune Therapy Center.