TKI258

An oral, potent inhibitor of FGFR, VEGFR, and PDGFR

The fibroblast growth-factor receptor (FGFR) family of receptor tyrosine kinases (RTK) and their ligands have been recently implicated in tumorigenesis.¹ Specifically, epidemiological and molecular studies have reported a variety of genetic alterations, including gene amplifications, chromosomal translocations and mutations, as well as aberrant protein expression of FGFs/FGFRs in several cancer types.² TKI258 is an orally bioavailable kinase inhibitor of the FGFRs.¹ In addition, its activity against VEGFR and PDGFR, along with the FGFR inhibitory activity, is responsible for the potent anti-angiogenic component of the compound.^1,3,4

TKI258 is now being investigated in phase I and II clinical trials in RCC and melanoma. Studies are planned in breast cancer, urothelial cancer, and myeloma.

All compounds are either investigational or studied in new indications. Efficacy and safety have not been established. There is no guarantee that they will become commercially available.

1. Choi D-Y, Toledo-Aral J-J, Lin HY, et al. Fibroblast growth factor receptor 3 induces gene expression primarily through Ras-independent signal transduction pathways. J Biol Chem. 2001;276:5116-5122.
2. Data on file. Novartis Pharma AG, Basel, Switzerland.
3. Lam JS, Leppert JT, Yu H, et al. Expression of the vascular endothelial growth factor family in tumor dissemination and disease free survival in clear cell renal cell carcinoma. Presented at: 42nd Annual Meeting of the American Society of Clinical Oncology. May 13-17, 2005; Orlando, Fla. Abstract 4538.
4. Carvalho I, Milanezi F, Martins A, Reis RM, Schmitt F. Overexpression of platelet-derived growth factor receptor A in breast cancer is associated with tumour progression. Breast Cancer Res. 2005;7:R788-R795.