Abstract
Solid tumors remain a major challenge for targeted therapeutic intervention strategies such as antibody-drug conjugates and immunotherapy. At a minimum, clear and actionable solid tumor targets have to comply with the key biological requirement of being differentially over-expressed in solid tumors and metastasis, in contrast to healthy organs. Oncofetal chondroitin sulfate is a cancer-specific secondary glycosaminoglycan modification to proteoglycans expressed in a variety of solid tumors and metastasis. Normally, this modification is found to be exclusively expressed in the placenta, where it is thought to facilitate normal placental implantation during pregnancy. Informed by this biology, oncofetal chondroitin sulfate is currently under investigation as a broad and specific target in solid tumors. Here, we discuss oncofetal chondroitin sulfate as a potential therapeutic target in childhood solid tumors in the context of current knowhow obtained over the past five years in adult cancers.
Highlights
In addition to the expression of proto-oncogenes, a number of oncofetal proteins are shared between placenta, tumors and fetal tissue, including pregnancy-associated plasma protein A (PAPP-A), PEG10, alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), trophoblast glycoprotein precursor (TPBG) and immature laminin receptor protein. Based on their oncofetal properties, some of these proteins have since been pursued as potential therapeutic targets in solid tumors
GAGs are large, linear, negatively-charged polysaccharides consisting of repeating disaccharide units that can be sulfated at different positions and to different extents [51,52]
Placental CSPGs are mainly located on trophoblast cells in the extracellular matrix (ECM) surrounding the expanding syncytium [63], where they are involved in a number of physiological processes
Summary
The placenta, an organ that develops during pregnancy, behaves in many ways like a tumor. In addition to the expression of proto-oncogenes, a number of oncofetal proteins are shared between placenta, tumors and fetal tissue, including pregnancy-associated plasma protein A (PAPP-A), PEG10, alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), trophoblast glycoprotein precursor (TPBG) and immature laminin receptor protein (iLRP). Based on their oncofetal properties, some of these proteins have since been pursued as potential therapeutic targets in solid tumors. Proteins that are not normally glycosylated may be subject to disease-specific glycosylations, thereby increasing the available tumor target reservoir [48,49,50]
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