Apoptosis, or programmed cell death, is a part of the normal life cycle of many, perhaps all, cell types and has emerged as a very important regulatory pathway in oncogenesis and in the pathogenesis of many human diseases. Apoptosis is used for the systematic elimination of excess, damaged, or hazardous somatic cells. It is a process by which the cell commits to cellular suicide in a systematic, highly energy dependent method of disassembly and packaging. Facilitating apoptosis selectively in the cancer cell is a mechanism by which oncotherapy may prove highly advantageous. Unfortunately, punctilious pursuit in understanding programmed cell death and the factors that influence it, even in the normal cell, has been a challenge. Conceptually, however, if an optimal understanding of the extrinsic (Fas-induced) apoptotic pathway can be garnered, with therapeutic targets revealed, a combined pro-death and anti-life clinical approach can be tailored to the renegade cancer cell. Our long-term goal is to facilitate the development of new pro-apoptotic targets in the bio-targeted treatment of mesenchymal neoplasia, and specifically sarcomas, by improving the understanding of the regulation of the extrinsic Fas ligand mediated death pathway. Initially, by fastidiously investigating the details of whether the FasL/EGFR/Fas relationship applies to mesenchyme, as described in hepatocytes (and hepatocellular carcinoma), we can establish a detailed working model of extrinsically induced apoptosis in mesenchymal neoplasia. As CTGF is known to positively affect fibroblastic proliferation, we will also gain an understanding of how this mesenchymal growth factor influences the FasL-mediated apoptotic pathway in sarcomagenesis. Only by understanding the details of these relationships can we then move forward, in partnership with medicinal chemistry, to specifically target these complex neoplastic pathways via a multi-interference approach.