Theranostics 2021; 11(7):3262-3277. doi:10.7150/thno.54023


Semaphorins as emerging clinical biomarkers and therapeutic targets in cancer

Roberta Mastrantonio1, Hua You2✉, Luca Tamagnone1,3✉

1. Università Cattolica del Sacro Cuore, Rome, Italy.
2. Affiliated Cancer Hospital & Institute of Guangzhou Medical University, China.
3. Fondazione Policlinico Universitario “A. Gemelli”, IRCCS, Rome, Italy.

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Mastrantonio R, You H, Tamagnone L. Semaphorins as emerging clinical biomarkers and therapeutic targets in cancer. Theranostics 2021; 11(7):3262-3277. doi:10.7150/thno.54023. Available from

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Semaphorins are a large family of developmental regulatory signals, characterized by aberrant expression in human cancers. These molecules crucially control cell-cell communication, cell migration, invasion and metastasis, tumor angiogenesis, inflammatory and anti-cancer immune responses. Semaphorins comprise secreted and cell surface-exposed molecules and their receptors are mainly found in the Plexin and Neuropilin families, which are further implicated in a signaling network controlling the tumor microenvironment. Accumulating evidence indicates that semaphorins may be considered as novel clinical biomarkers for cancer, especially for the prediction of patient survival and responsiveness to therapy. Moreover, preclinical experimental studies have demonstrated that targeting semaphorin signaling can interfere with tumor growth and/or metastatic dissemination, suggesting their relevance as novel therapeutic targets in cancer; this has also prompted the development of semaphorin-interfering molecules for application in the clinic. Here we will survey, in diverse human cancers, the current knowledge about the relevance of semaphorin family members, and conceptualize potential lines of future research development in this field.

Keywords: prognostic biomarkers, predictive biomarkers, therapy, cancer, semaphorin, plexin, neuropilin