德國(guó)科學(xué)家在患常見(jiàn)肺癌的吸煙者體內(nèi)發(fā)現(xiàn)了一種基因變異，可供科學(xué)家有針對(duì)性地研制新型抗癌藥物,。研究結(jié)果發(fā)表在《科學(xué)轉(zhuǎn)化醫(yī)學(xué)》雜志上,。
倫敦癌癥研究所的 Nicholas Turner說(shuō)：“目前，對(duì)于患有這種癌癥的患者來(lái)說(shuō),，情況一點(diǎn)都不妙,。”但他表示，這份研究提供了一絲希望,。他在同一本雜志上撰寫(xiě)了一篇評(píng)論文章,。
據(jù)世界衛(wèi)生組織數(shù)據(jù)，肺癌是全世界癌癥死亡的頭號(hào)病因,，每年多達(dá)130萬(wàn)人因肺癌死亡,，其中大部分是源于吸煙。
來(lái)自德國(guó)馬克斯・普朗克神經(jīng)研究所（Max Planck Institute for Neurological Research）的羅曼・托馬斯（Roman Thomas）是該研究的負(fù)責(zé)人,。他發(fā)現(xiàn)鱗狀細(xì)胞肺癌的細(xì)胞樣本比其他癌細(xì)胞樣本含有更多的FGFR1基因,。
托馬斯表示，研究成果顯示,，F(xiàn)GFR阻滯劑一類(lèi)的藥物可能對(duì)治療鱗狀細(xì)胞肺癌有效,。（生物谷Bioon.com）
生物谷推薦原文出處：
Sci Transl Med DOI: 10.1126/scitranslmed.3001451
Frequent and Focal FGFR1 Amplification Associates with Therapeutically Tractable FGFR1 Dependency in Squamous Cell Lung Cancer
Jonathan Weiss1,*, Martin L. Sos1,*? , Danila Seidel1,2,*, Martin Peifer1, Thomas Zander3, Johannes M. Heuckmann1, Roland T. Ullrich1, Roopika Menon4, Sebastian Maier4, Alex Soltermann5, Holger Moch5, Patrick Wagener6, Florian Fischer1, Stefanie Heynck1, Mirjam Koker1, Jakob Sch?ttle1, Frauke Leenders1,2, Franziska Gabler1,2, Ines Dabow1,2, Silvia Querings1, Lukas C. Heukamp7, Hyatt Balke-Want1, Sascha Ansén3, Daniel Rauh8, Ingelore Baessmann9, Janine Altmüller9, Zoe Wainer10, Matthew Conron10, Gavin Wright10, Prudence Russell11, Ben Solomon12, Elisabeth Brambilla13,14, Christian Brambilla13,14, Philippe Lorimier13, Steinar Sollberg15, Odd Terje Brustugun16,17, Walburga Engel-Riedel18, Corinna Ludwig18, Iver Petersen19, J?rg S?nger20, Joachim Clement21, Harry Groen22, Wim Timens23, Hannie Sietsma23, Erik Thunnissen24, Egbert Smit25, Dani?lle Heideman24, Federico Cappuzzo26, Claudia Ligorio27, Stefania Damiani27, Michael Hallek3,28, Rameen Beroukhim29,30,31,32, William Pao33, Bert Klebl34, Matthias Baumann34, Reinhard Buettner7, Karen Ernestus35, Erich Stoelben18, Jürgen Wolf2,3, Peter Nürnberg8,28, Sven Perner4 and Roman K. Thomas1,2,3,7,?
Abstract
Lung cancer remains one of the leading causes of cancer-related death in developed countries. Although lung adenocarcinomas with EGFR mutations or EML4-ALK fusions respond to treatment by epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibition, respectively, squamous cell lung cancer currently lacks therapeutically exploitable genetic alterations. We conducted a systematic search in a set of 232 lung cancer specimens for genetic alterations that were therapeutically amenable and then performed high-resolution gene copy number analyses. We identified frequent and focal fibroblast growth factor receptor 1 (FGFR1) amplification in squamous cell lung cancer (n = 155), but not in other lung cancer subtypes, and, by fluorescence in situ hybridization, confirmed the presence of FGFR1 amplifications in an independent cohort of squamous cell lung cancer samples (22% of cases). Using cell-based screening with the FGFR inhibitor PD173074 in a large (n = 83) panel of lung cancer cell lines, we demonstrated that this compound inhibited growth and induced apoptosis specifically in those lung cancer cells carrying amplified FGFR1. We validated the FGFR1 dependence of FGFR1-amplified cell lines by FGFR1 knockdown and by ectopic expression of an FGFR1-resistant allele (FGFR1V561M), which rescued FGFR1-amplified cells from PD173074-mediated cytotoxicity. Finally, we showed that inhibition of FGFR1 with a small molecule led to significant tumor shrinkage in vivo. Thus, focal FGFR1 amplification is common in squamous cell lung cancer and associated with tumor growth and survival, suggesting that FGFR inhibitors may be a viable therapeutic option in this cohort of patients.
