VIEWING HEART FAILURE AS INTERSTITIAL CANCER: DIAGNOSTIC AND THERAPEUTIC AVENUES
Frank Spinale, M.D., Ph.D., University of South Carolina School of Medicine, Columbia, SC, USA
In contrast to public perception, the morbidity and mortality as well as the resultant health care costs associated with chronic heart failure (HF) are increasing and arguably reaching epidemic proportions, but improvements in diagnostic and therapeutic strategies for this disease have not been forthcoming. The factors that contribute to this relative paucity of new clinical tools for HF are multifactorial but likely include the need to recognize and differentiate HF phenotypes and to move beyond conventional thought regarding biological pathways, which regulate myocardial growth and function. To that end, there are many lessons that can be learned from research in the cancer field that are potentially translatable to the HF process. For example, the most numerous cell type in the heart is the fibroblast, and with HF, this cell type undergoes a differentiation process not dissimilar to that of cancer metastasis. Specifically, HF myocardial fibroblasts express transcriptional and protein markers similar to those observed in a process of mesenchymal-epithelial transformation described in cancer. Moreover, this laboratory and others have identified proteolytic enzymes which degrade the tissue space - the extracellular matrix (ECM) emerges in both patients and animal models of HF. The aims of this presentation will be 3-fold. First, examine and identify the phenotype classifications of clinical HF and relate these phenotypes to abnormalities in ECM and fibroblast growth and function. Second, present basic and translational studies regarding fibroblast transformation in HF and pathways that may form therapeutic targets, which may actually parallel chemotherapeutic strategies. Third, present new studies regarding novel molecular imaging approaches and therapeutics for HF.
The conclusion to be drawn is that new findings in cancer research can be translated to target the transdifferentiated fibroblast in HF as a form of interstitial cancer.