Targets for Anti-metastatic Drug Development

Anna-Maria      Stock; Gabriele      Troost; Bernd      Niggemann; Kurt   S.   Zanker; Frank      Entschladen

Abstract

With a constant focus on the primary tumor, the current approaches in drug development in oncology yield dismal results. However over 90 percent of cancer deaths today are due to metastasis formation and yet there is no anti-metastatic drug on the market. Tumor cell migration is the essential prerequisite for invasion and metastasis formation. It is regulated by signal substances in terms of the grade of activity and in terms of direction (chemotaxis). The latter is important for the organotropism, the localization of metastasis in certain organs. Ligands to G protein-coupled receptors, mainly chemokines and neurotransmitters, as well as ligands to receptor kinases, mainly cytokines and growth factors, form the most important group of such regulators. We provide an overview of currently available agonists and antagonists to these receptors, which have a potential as anti-metastatic targets. Moreover we provide with the example of beta-blockers, how established drugs in other indications are possibly effective and can be co-opted as such anti-metastatics. The increasing knowledge of such regulators opens new opportunities to target cancer spreading and may put forth the development of antimetastatic drugs for oncological therapy.

Keywords: Metastasis, invasion, cell migration, chemokines, cytokines, neurotransmitters.

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