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Neurotrophin Trk Receptors: New Targets for Cancer Therapy

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Reviews of Physiology, Biochemistry and Pharmacology Vol. 174

Part of the book series: Reviews of Physiology, Biochemistry and Pharmacology ((REVIEWS,volume 174))

Abstract

In the last few years, exciting reports have emerged regarding the role of the two types of neurotrophin receptors, p75NTR and Trks, not only in neurons, where they were discovered, but also in non-neural cells and, especially, in numerous cancers, including breast, lung, colon-rectum, pancreas, prostate, glioblastoma, neuroblastoma, myeloma, and lymphoid tumors. Traditionally, p75NTR, activated by all neurotrophins and their precursors, is an inhibitor. In various cancers, however, activated p75NTR induces variable effects, from inhibition to stimulation of cell proliferation, dependent on their direct or coordinate/indirect mechanism(s) of action. TrkA, TrkB, and TrkC, activated by distinct neurotrophins, are high affinity stimulatory receptors. In cancers, activation of Trks, especially of TrkB, are stimulators of cell proliferation, aggressiveness, and metastases. In rare cancers, these processes are due not to receptor activation but to fusion or mutation of the encoding genes. A considerable panel of anti-Trk drugs, developed recently, has been investigated both in vitro and in living mice for their effects on cancer cells. Many such drugs protect from cancers by preventing cell proliferation and inducing apoptosis. At present, these drugs are under control by trials, to promote introduction in human therapy. Moreover, anti-Trk drugs have been employed also in combination with classical chemotherapeutic drugs. So far, studies in mice have been positive. The chemotherapeutic/anti-receptor combinations exhibited in fact increased potency and down-regulation of resistance, with no increase of side effects.

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Authors and Affiliations

  1. Department of Neuroscience, Scientific Institute San Raffaele, Vita-Salute San Raffaele University, Milan, Italy

    Jacopo Meldolesi

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  1. Jacopo Meldolesi
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Correspondence to Jacopo Meldolesi .

Editor information

Editors and Affiliations

  1. Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium

    Bernd Nilius

  2. Heart Science Centre, The Magdi Yacoub Institute, Harefield, United Kingdom

    Pieter de Tombe

  3. Walther-Straub Institute for Pharmacology and Toxicology, Ludwig-Maximilians University of Munich, Munich, Germany

    Thomas Gudermann

  4. Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany

    Reinhard Jahn

  5. Department of Cytobiology, University of Marburg , Marburg, Germany

    Roland Lill

  6. Cardiff School of Biosciences, Cardiff University, Cardiff, United Kingdom

    Ole H. Petersen

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Meldolesi, J. (2017). Neurotrophin Trk Receptors: New Targets for Cancer Therapy. In: Nilius, B., de Tombe, P., Gudermann, T., Jahn, R., Lill, R., Petersen, O. (eds) Reviews of Physiology, Biochemistry and Pharmacology Vol. 174. Reviews of Physiology, Biochemistry and Pharmacology, vol 174. Springer, Cham. https://doi.org/10.1007/112_2017_6

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