Tumor Cell Motility as a Novel Target in Cancer – Experimental and Clinical Results

Abstract

Background: Surgery, chemotherapy and radiotherapy are the mainstay of tumor management. However, in systemic disease cure can be achieved in yet a few tumor entities. Based on cellbiological research we have characterized the process of tumor progression and metastasis and disclosed that the loss of cell-cell adhesion in association with an increased tumor cell motility is an essential feature of the malignant potential of a tumor. Methods: According to this principle we derived therapeutical methods differing from hitherto existing treatments by being exclusively focused on tumor cell motility. Characterization of so-called anti-motility factors was performed biochemically as well as with motility assays by in vitro studies in established bladder carcinoma cell lines. Results: We evaluated the potential therapeutic benefit in a model of chemically induced bladder carcinoma followed by a phase I/II trial applying antimotility factors in patients with advanced bladder cancer. Conclusion: Both basic research as well as the results of first clinical trials confirm, that advanced carcinomas can be influenced by inhibition of tumor cell motility.

Perioperative Chemotherapy in Advanced Bladder Cancer: Part I Neoadjuvant Treatment

“…Among such possible target pathways are Ras-mediated mitogenic and transformation signals [31], human epidermal growth factor receptor 2 [32] and epidermal growth factor receptor-mediated perturbations of the microenvironment [33]. Other efforts focus on tumor cell motility [34], the vascular endothelial growth factor-mediated regulation of tumor angiogenesis [35], and the insulin-like growth factor 1 receptor-mediated signals in progression, invasion and metastasis of bladder cancer cells [36]. Several candidates for selective inhibitors (such as STI-571, ZD-1839, OSI-774, flavopiridol, herceptin and C225) are currently evaluated in preclinical and clinical trials in a variety of tumor entities [37] and will also have strong impact on the understanding and management of bladder cancer.…”