BMC Research Notes | |
Acquired drug resistance conferred by a KRAS gene mutation following the administration of cetuximab: a case report | |
Toshiharu Yamaguchi2  Nobuyuki Mizunuma3  Masashi Ueno2  Akio Saiura2  Mun Mingyon1  Mitsukuni Suenaga3  Eiji Shinozaki3  Satoshi Matsusaka3  Hiroki Osumi3  | |
[1] Thoracic Center, Koto-ku, Japan;Surgery, Koto-ku, Japan;Department of Gastroenterology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, 135-8550, Koto-ku, Tokyo, Japan | |
关键词: Cetuximab; Acquired resistance; KRAS; | |
Others : 1140595 DOI : 10.1186/1756-0500-6-508 |
|
received in 2013-06-21, accepted in 2013-11-28, 发布年份 2013 | |
【 摘 要 】
Background
Although a number of studies have reported acquired drug resistance due to administration of epidermal growth factor receptor antibody inhibitors, the underlying causes of this phenomenon remain unclear.
Case presentation
Here we report a case of a 75-year-old man with liver metastasis at 3 years after a successful transverse colectomy to treat KRAS wild-type colorectal cancer. While initial administration of epidermal growth factor receptor inhibitors proved effective, continued use of the same treatment resulted in new peritoneal seeding. An acquired KRAS mutation was found in a resected tissue specimen from one such area. This mutation, possibly caused by administration of epidermal growth factor receptor inhibitors, appears to have conferred drug resistance.
Conclusion
The present findings suggest that administration of epidermal growth factor receptor inhibitors results in an acquired KRAS mutation that confers drug resistance.
【 授权许可】
2013 Osumi et al.; licensee BioMed Central Ltd.
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
20150325054305376.pdf | 495KB | download | |
Figure 3. | 61KB | Image | download |
Figure 2. | 56KB | Image | download |
Figure 1. | 55KB | Image | download |
【 图 表 】
Figure 1.
Figure 2.
Figure 3.
【 参考文献 】
- [1]Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, Nakamura Y, White R, Smits AM, Bos JL: Genetic alterations during colorectal-tumor development. N Engl J Med 1998, 319:525-532.
- [2]Han CB, Li F, Ma JT, Zou HW: Concordant KRAS mutations in primary and metastatic colorectal cancer tissue specimens: a meta-analysis and systematic review. Cancer Invest 2012, 30(10):741-747.
- [3]Watanabe T, Kobunai T, Yamamoto Y, Matsuda K, Ishihara S, Nozawa K, Iinuma H, Shibuya H, Eshima K: Heterogeneity of KRAS status may explain the subset of discordant KRAS status between primary and metastatic colorectal cancer. Dis Colon Rectum 2011, 54(9):1170-1178.
- [4]Knijn N, Mekenkamp LJ, Klomp M, Vink-Börger ME, Tol J, Teerenstra S, Meijer JW, Tebar M, Riemersma S, Van Krieken JH, Punt CJ, Nagtegaal ID: KRAS mutation analysis: a comparison between primary tumours and matched liver metastases in 305 colorectal cancer patients. Br J Cancer 2011, 104(6):1020-1026.
- [5]Ciardiello F, Tortora G: EGFR antagonists in cancer treatment. N Engl J Med 2008, 358:1160-1174.
- [6]Bouchahda M, Karaboué A, Saffroy R, Innominato P, Gorden L, Guettier C, Adam R, Lévi F: Acquired KRAS mutations during progression of colorectal cancer metastases: possible implications for therapy and prognosis. Cancer Chemotherapy Pharmacol 2010, 66(3):605-609.
- [7]Misale S, Yaeger R, Hobor S, Scala E, Janakiraman M, Liska D, Valtorta E, Schiavo R, Buscarino M, Siravegna G, Bencardino K, Cercek A, Chen CT, Veronese S, Zanon C, Sartore-Bianchi A, Gambacorta M, Gallicchio M, Vakiani E, Boscaro V, Medico E, Weiser M, Siena S, Di Nicolantonio F, Solit D, Bardelli A: Emergence of KRAS mutation and acquired resistance to anti-EGFR therapy in colorectal cancer. Nature 2012, 486(7404):532-536.
- [8]Diaz LA Jr, Williams RT, Wu J, Kinde I, Hecht JR, Berlin J, Allen B, Bozic I, Reiter JG, Nowak MA, Kinzler KW, Oliner KS, Vogelstein B: The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers. Nature 2012, 486(7404):537-540.
- [9]Li Z, Jin K, Lan H, Teng L: Heterogeneity in primary colorectal cancer and its corresponding metastases: a potential reason of EGFR-targeted therapy failure? Hepatogastroenterology 2011, 58(106):411-416.
- [10]Bardelli A, Jänne PA: The road to resistance : EGFR mutation and cetuximab. Nature medicine 2012, 18:199-200.
- [11]Montagut C, Dalmases A, Bellosillo B, Crespo M, Pairet S, Iglesias M, Salido M, Gallen M, Marsters S, Tsai SP, Minoche A, Seshagiri S, Serrano S, Himmelbauer H, Bellmunt J, Rovira A, Settleman J, Bosch F, Albanell J: Identification of a mutation in the extracellular domain of the epidermal growth facter receptor conferring cetuximab resistance in colorectal cancer. Nature medicine 2012, 18(2):221-223.