Placental growth factor in cancer

Abstract

Introduction: Placental growth factor (PLGF) belongs to the VEGF family, which among the three VEGF receptors binds exclusively to VEGFR1, present on various cell types. Isoform PLGF-2 also binds the neuropilin co-receptors. PLGF is dispensable for development and health but has a prominent role in pathology including cancer. This has triggered the question whether PLGF targeting might offer an alternative to current antiangiogenesis therapy, which encounters problems of refractoriness and acquired resistance.

Areas covered: This article reviews the available literature on the characteristics of PLGF, its role(s) in cancer and the findings on PLGF inhibition in preclinical models with attention to as yet unresolved questions and summarizes data from initial clinical trials.

Expert opinion: Preclinical studies show that inhibition of PLGF, either by genetic inhibition or by pharmacological blockade using distinct independently generated anti-PLGF antibodies, slows down tumor growth and metastasis and even induces regression of pre-existing medulloblastoma, the most frequent brain cancer in children. These promising preclinical findings, together with the acceptable safety profile of anti-PLGF administration in Phase I clinical trials, have attracted attention to PLGF as a potential target for therapy.

Keywords::

• angiogenesis
• cancer
• inflammation
• macrophage polarization
• metastasis
• placental growth factor
• targeted therapy

Acknowledgements

This work is supported in part by the Belgian Science Policy (IUAP07/03), long-term structural Methusalem funding by the Flemish Government, and a European Research Council Advanced Research Grant (EU-ERC269073) to PC, and by grants from FWO-Vlaanderen and by the Foundation against Cancer, foundation of public interest, to MD and PC.

Notes

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