Crenolanib - PDGFR

PDGFR and Human Cancer

PDGF-activated pathways play a central role in a number of human malignancies through its translocation, amplification and activation point mutation, and/or over expression of its receptors or ligands.


Dermatofibrosarcoma protuberans (DFSP) is caused due to translocation of the PDGFB gene to the COL1A1 gene.1


·         PDGFRA amplifications are observed in about 12% of high grade pediatric gliomas.2

·         Some gliomas are found to have a deletion mutation in PDGFRA which is constitutively active.3

·         5-12% of the gastrointestinal stromal tumors (GIST) are caused by activating point mutations and small deletions in the PDGFRA gene.4

·         PDGFRA activation has been reported in up to 13% of non-small cell lung cell carcinomas, with squamous cell carcinoma being the most common. 5

·         Idiopathic hypereosinophilic syndrome (IHES) is caused due to fusion of the PDGFRA gene with the genes FIP1L1, K1F5B, or CDKRAP2 in approximately 10-30% of the cases.6

·         Exon 12 mutations of PDGFRA are responsible for inflammatory fibroid polyps which represent polypous proliferations of spindle cells in the submucosa and mucosa of the stomach, small bowel, and colon with inflammatory infiltration.7


Chronic myelomonocytic leukemia (CMML) is caused by fusion of the PDGFRB gene with the TEL gene in approximately 30% of the cases.8


1Wang et al. Diagn Mol Pathol. 1999; 8(3):113-119
2Paugh et al. J Clin Oncol. 2010; 28(18):3061-3068
3Clarke, et al. Oncogene 2003; 22:722-733
4Heinrich, et al. J Clin Oncol. 2003; 21(23):4342-4349
5Ramos, et al. Cancer Biol Ther. 2009; 8(21):2042-2050
6Östman et al. Adv Cancer Res. 2007; 97:247-274
7Schildhaus et al. J Pathol. 2008; 216(2):176-182
8Golub et al. Cell 1994; 77(2):307-316