Imatinib (UK: Glivac®; US: Gleevac®) is a relatively low potency tyrosine kinase (KIT) inhibitor used in the treatment of Philadelphia-positive chronic myeloid leukaemia and KIT positive gastrointestinal stromal tumours. It is one of several examples of where understanding of the steps in carcinogenesis have allowed targetting of specific molecular targets.
In GIST, response to imatinib can be assessed using PET or CT scanning. A good response supports the continued usage of the drug, whereas a poor response, not surprisingly, predicts a lack of efficacy. Secondary resistance to the drug may be a result of selection for a Ser650Thr missense mutation.
- Inhibits various tyrosine kinases.
- Therapeutic application involves direct binding to the fusion protein BCR-ABL which has components from breakpoint cluster region protein and tyrosine kinase Abelson murine leukaemia protein (ABL).
- Inhibits ABL hence as c-ABL mediates tumour suppressor effects of the EphB4 receptor could promote epithelial tumour progression. 
- Inhibits Platelet-derived growth factor receptor
- Inhibits Jun N-terminal kinase(JNK) pathway (hence heart failure as above)
- More susceptible to resistance developing due to the way it binds to the receptor BCR-ABL domain in chronic myeloid leukaemia
NICE Guidance: http://www.nice.org.uk/page.aspx?o=TA086
- ↑ Negri T, Pavan GM, Virdis E, Greco A, Fermeglia M, Sandri M, Pricl S, Pierotti MA, Pilotti S, Tamborini E. T670X KIT mutations in gastrointestinal stromal tumors: making sense of missense. Journal of the National Cancer Institute. 2009 Feb 4; 101(3):194-204.(Link to article – subscription may be required.)
- ↑ Park YH, Park HJ, Kim BS, Ha E, Jung KH, Yoon SH, Yim SV, Chung JH. BNP as a marker of the heart failure in the treatment of imatinib mesylate. Cancer Lett. 2005
- ↑ Kerkela R, Grazette L, Yacobi R, Iliescu C, Patten R, Beahm C, Walters B, Shevtsov S, Pesant S, Clubb FJ, Rosenzweig A, Salomon RN, Van Etten RA, Alroy J, Durand JB, Force T. Cardiotoxicity of the cancer therapeutic agent imatinib mesylate. Nat Med. 2006 Jul 23
- ↑ Noren NK, Foos G, Hauser CA, Pasquale EB. The EphB4 receptor suppresses breast cancer cell tumorigenicity through an Abl-Crk pathway. Nature cell biology. 2006;8:815-25. (Direct link – subscription may be required.)
- ↑ Noren NK, Lu M, Freeman AL, Koolpe M, Pasquale EB. Interplay between EphB4 on tumor cells and vascular ephrin-B2 regulates tumor growth. Proceedings of the National Academy of Sciences of the United States of America. 2004;101:5583-8. (Direct link – subscription may be required.)
- ↑ KerkelÃ¤ R, Grazette L, Yacobi R, Iliescu C, Patten R, Beahm C, et al. Cardiotoxicity of the cancer therapeutic agent imatinib mesylate. Nature medicine. 2006;12:908-16. (Direct link – subscription may be required.)