The potential of class 3 semaphorins as both targets and therapeutics in cancer

Abstract

Introduction: Semaphorins have been originally identified as a family of evolutionary conserved soluble or membrane-associated proteins involved in diverse developmental phenomena. This family of proteins profoundly influences numerous pathophysiological processes, including organogenesis, cardiovascular development and immune response. Apart from steering the neural networking process, these are implicated in a broad range of biological operations including regulation of tumor progression and angiogenesis.

Areas covered: Members of class 3 semaphorin family are known to modulate various cellular processes involved in malignant transformation. Some of the family members trigger diverse signaling processes involved in tumor progression and angiogenesis by binding with plexin and neuropilin. A better understanding of the various signaling mechanisms by which semaphorins modulate tumor progression and angiogenesis may serve as crucial tool in crafting new semaphorin-based anticancer therapy. These include treatment with recombinant tumor suppressive semaphorins or inhibition of tumor-promoting semaphorins by their specific siRNAs, small-molecule inhibitors or specific receptors using neutralizing antibodies or blocking peptides that might serve as novel strategies for effective management of cancers.

Expert opinion: This review focuses on all the possible avenues to explore various members of class 3 semaphorin family to serve as therapeutics for combating cancer.

Keywords:

• angiogenesis
• metastasis
• neuropilin
• plexin
• RNAi technology
• semaphorin
• small-molecule inhibitors
• targeted therapy
• tumor microenvironment

Declaration of interest

The author’s research is supported in part by Department of Biotechnology, Department of Science and Technology and Council of Scientific and Industrial Research, Government of India. We apologize to the many colleagues whose contributions we could not cite because of limitation of space. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Notes

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