The PDGF/PDGFR Pathway as a Drug Target

The document reviewed the PDGF/PDGFR pathway's role in diseases such as cancer, fibrosis, neurological conditions, and atherosclerosis, and its potential as a drug target. It detailed the activation of PDGF signaling and the challenges in developing specific inhibitors due to structural similarities with other tyrosine kinases. Therapeutic strategies include various inhibitors, with olaratumab being approved in the USA and conditionally in the EU for advanced soft tissue sarcoma. However, olaratumab was ineffective for other solid tumors, and two phase II trials were terminated. Preclinical studies showed potential for DNA/RNA aptamers, but clinical testing has not been performed. Tyrosine kinase inhibitors (TKIs) like imatinib have been successful in treating hematological malignancies but have specificity issues. The document also discussed the variable therapeutic effects of targeting the PDGF/PDGFR axis in cancer, the questionable efficacy of TKIs in neurological diseases, the lack of effective PDGF antagonists for atherosclerosis, and some success in reducing fibrosis in animal models. It suggested that human organoids could complement preclinical testing and referenced databases for tracking drug development.