Cancer can develop in any organ or tissue, and is highly refractory and lethal. It goes without saying that cancer is a highly cumbersome disease. Recent statistical data show that one out of every two people is diagnosed with cancer during his/her lifetime, and one out of four men and one out of six women die of cancer. Thus, cancer remains an extremely serious disease.
Fibroblast growth factor receptors (FGFRs) are kinases belonging to the receptor tyrosine kinase family. FGFR1, FGFR2, FGFR3, and FGFR4 constitute the FGFR family. The ligand is fibroblast growth factor (FGF), and 22 types of structurally similar proteins form the family.
Signals transmitted via FGFR are conveyed to the MAPK pathway or PI3K/AKT pathway. It has been reported that in cancer, signal transduction is involved in cell growth, angiogenesis, cell migration, invasion, metastasis, etc.; and FGFR is activated as a result of overexpression, gene hyper-amplification, mutation, or translocation (Non-patent Document 1). For example, it is known that for FGFR3, genetic translocation is observed in multiple myeloma (Non-patent Document 2); gene mutation is observed in bladder cancer (Non-patent Document 3); and overexpression is observed in ovarian cancer, non-small cell lung carcinoma, and hepatocellular carcinoma.
The findings described above suggest a connection between FGFR and cancer. Thus, attempts have been made to develop compounds with FGFR-inhibitory activity as anticancer agents (Non-patent Documents 4 and 5).
Currently, various molecule-targeting drugs specific to various types of kinases are commercially available. However, certain amino acid mutations in EGFR tyrosine kinase which is a target molecule of gefitinib, erlotinib, and such, have become the main cause for acquisition of resistance to gefitinib, erlotinib, and such. Such mutations are called gatekeeper (GK) mutations, and there have been reports on GK mutations in FGFR2 as well (Non-Patent Document 6).
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