The key obstacle for a breakthrough in cancer therapeutics is that tumors are thought to result from the unregulated growth of a single cell type that has accumulated random gene mutations, whereas the true mark of malignancy is the ability of cancerous cells to break down tissue architecture, invade through the disrupted tissue boundaries and metastasize to distant organ sites. TAFs have an established biological impact on tumorigenesis due to their role as matrix synthesizing or matrix degrading cells, contractile cells (a-SMA expression), and even blood vessel associated cells (VEGF secretion). Furthermore, our group has recently provided compelling evidence to support the origin of TAFs from bone marrow mesenchymal stem cells, which can be recruited to tumor site, where they proliferate and aquire a TAF-like phenotype (Paunescu et al., J Cell Mol Med, 2011). Tumor cell heterogeneity and variety is overwhelming, depending on the tissue from where the tumor has originated, the patient's genetic background, the antigenic drift during tumor progression, making them elusive targets for cancer therapy; however, TAFs can be conveniently similar in their origin, phenotype and genotype, regardless of the cancer type. Being genetically more stable than the frequently mutating, heterogenous tumor cell populations, the expression of the target TAF antigen will remain more constant and serve as a reliable target for therapy. The approach focused on tumor-associated fibroblasts promises to fulfill the criteria of personalized medicine, as the cytotoxic, tumor-fighting lymphocytes are the patient's own cells, while at the same time lowers the costs of therapy by standardizing a protocol to be applied for all types of cancers. As our on-going research on TAFs uncovers novel antigenic targets, the flexibility of the Streptamer technology will allow us to select ever more specific CTLs at the same resource expenditure.