Class 3 semaphorins: physiological vascular normalizing agents for anti-cancer therapy

Authors

  • G. Serini,

    1. Institute for Cancer Research at Candiolo (IRCC), University of Torino, Turin, Italy
    2. Department of Oncology, University of Torino, Turin, Italy
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  • F. Bussolino,

    1. Institute for Cancer Research at Candiolo (IRCC), University of Torino, Turin, Italy
    2. Department of Oncology, University of Torino, Turin, Italy
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  • F. Maione,

    1. Institute for Cancer Research at Candiolo (IRCC), University of Torino, Turin, Italy
    2. Department of Science and Drug Technology, University of Torino, Turin, Italy
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  • E. Giraudo

    Corresponding author
    1. Institute for Cancer Research at Candiolo (IRCC), University of Torino, Turin, Italy
    2. Department of Science and Drug Technology, University of Torino, Turin, Italy
    • Correspondence: Enrico Giraudo PhD, Department of Science e Drug Technology, University of Torino and Laboratory of Transgenic Mouse Models, Institute for Cancer Research at Candiolo (IRCC), Strada Provinciale 142, Km 3.95, I-10060 Candiolo, Turin, Italy.

      (fax: +39-011-9933524; e-mail: enrico.giraudo@ircc.it).

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Abstract

Findings from preclinical and clinical studies show that vascular normalization represents a novel strategy to enhance the efficacy of and overcome the acquired resistance to anti-angiogenic therapies in cancer. Several mechanisms of tumour vessel normalization have been revealed. Amongst them, secreted class 3 semaphorins (Sema3), which regulate axon guidance and angiogenesis, have been recently identified as novel vascular normalizing agents that inhibit metastatic dissemination by restoring vascular function. Here, we discuss the different biological functions and mechanisms of action of Sema3 in the context of tumour vascular normalization, and their impact on the different cellular components of the tumour microenvironment.

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