Parallels in Canonical Developmental Signaling Pathways between Normal Development and the Tumor Microenvironment

The tumor microenvironment (TME) is comprised of both cellular and stromal elements and plays an essential role in the growth, survival, and dissemination of malignancies. The TME is an organized program that develops with a growing tumor, using many processes involved in normal tissue development. In multiple solid tumors, developmental pathways are used to recruit immunosuppressive cells, including immunosuppressive monocytes and neutrophils, tumor-associated macrophages, and regulatory T cells to block the antitumor immune response. In addition, stromal cells sustain tumor growth via trophic support, angiogenesis, repair mechanisms, and associated immunosuppression, driven, at least in part, by canonical developmental signaling pathways. The microenvironmental ecosystem shapes tumor progression from its earliest inception by modulating important programs that dictate tumor behavior, necessitating further consideration when studying the developmental origins of malignancy. Here, we review the role of developmental pathways in the formation and modulation of the TME in pediatric and adult solid tumors, including Wnt, Notch, Hippo, Hedgehog, TGF-β, BMP, SOX, and OCT.