Article

PDGF Receptors as Targets in Tumor Treatment

Uppsala University, Uppsala, Uppsala, Sweden
Advances in Cancer Research (Impact Factor: 5.32). 02/2007; 97:247-74. DOI: 10.1016/S0065-230X(06)97011-0
Source: PubMed

ABSTRACT

Signaling through platelet-derived growth factor (PDGF) receptors contributes to multiple tumor-associated processes. The recent introduction of clinically useful PDGF inhibitors have the last years validated PDGF receptors in malignant and stromal cells as relevant cancer drug targets. Mutational activation of PDGF receptor signaling in malignant cells has been described in some rare tumor types such as dermatofibrosarcoma protuberans, a subset of GISTs, and some hematologic malignancies. Furthermore, expression of PDGF receptors on pericytes is a common characteristic of solid tumors. The clinical efficacy of novel multikinase inhibitors, such as sunitinib and sorafenib, most likely involves targeting of PDGF receptor-dependent pericytes. Preclinical studies suggest that targeting of stromal PDGF receptors might also constitute a novel strategy to enhance tumor drug uptake. Finally, recent studies have implied both pro- and antimetastatic effects of PDGF receptors on malignant and stromal cells. The studies on the roles of PDGF receptors in cancer signaling are thus presently in a dynamic phase where collaborations between oncologists, pathologists, and tumor biologists are predicted to be highly productive.

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Available from: Carl-Henrik Heldin, Dec 04, 2014
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    • "These signaling pathways promote cell proliferation, migration and survival. Overactivity of PDGF pathways is implicated in diseases involving excessive cell growth, including malignancies, cardiovascular disease and fibrosis [3]. "
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    • "Expression of PDGFRs is mainly restricted to mesenchymal cell types [2]. Activating mutations in PDGFRs are found in gastrointestinal stromal tumors [1]. In colorectal carcinomas, PDGFR expression appears to be mainly expressed by stromal cells and pericytes [4] [5]. "
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