找到耐药基因肺癌治愈率提高

suyagirl

哦，好呀好呀，癌症本来就是人体免疫机能下降引起的细胞突变，如果可以找到耐药基因，那么药物耐药时间越长越好，度过了人体机能的衰弱期，达到稳定期，癌细胞自然就会消失。

一路小跑

       天佑妈咪，这个药，省院吴一龙现在有给病人用吗？

坚强小鱼

这可算是个好消息。好像论坛里有病友和吴一龙熟悉的，顶起来大家落实一下。

天佑妈咪

原帖由 一路小跑 于 2010-1-26 21:49 发表

       天佑妈咪，这个药，省院吴一龙现在有给病人用吗？

我也是今天才看到报纸，打算星期四去省医问问。有什么消息马上告诉大家

坚强小鱼

原帖由 天佑妈咪 于 2010-1-26 23:54 发表


我也是今天才看到报纸，打算星期四去省医问问。有什么消息马上告诉大家

严重关注你的消息！愿上帝祝福我们。

jclzx_98

原帖由 天佑妈咪 于 2010-1-26 13:19 发表
前面大部分内容应该是你说的意思，但“这次中美两国专家开展的研究，不但找到耐药基因，还找出了抑制耐药基因的办法，”这句却给我们带来了新希望

是呀，看到这句确实令人激动，但后面这句就又让我一头雾水了。。。
  “研究人员发现，如果用药抑制MET基因的扩增，可以使肺癌靶向治疗的有效率从71%提高到93%。”
这里只提到了提高有效率，可并没有说可以延长耐药时间，是还需要时间来进行科学实验吗？ 非常关注此消息的后续报道~~~
感谢楼主：）

gosentqiji

关键是抑制MET的药现在有没有啊? 真的太急迫了啊.......知道消息的一定要来通知下啊.....

jimmy112199

这是论文的文摘部分， 全文见
http://download.cell.com/cancer- ... f?intermediate=true

Cancer Cell
Article
Preexistence and Clonal Selection
of MET Amplification in EGFR Mutant NSCLC
Alexa B. Turke,1,2,10 Kreshnik Zejnullahu,3,4,10 Yi-Long Wu,5 Youngchul Song,1 Dora Dias-Santagata,1 Eugene Lifshits,1
Luca Toschi,3,4 Andrew Rogers,3,4 Tony Mok,6 Lecia Sequist,1 Neal I. Lindeman,7 Carly Murphy,7 Sara Akhavanfard,1
Beow Y. Yeap,1,2 Yun Xiao,4,7 Marzia Capelletti,3,4 A. John Iafrate,1 Charles Lee,7 James G. Christensen,8
Jeffrey A. Engelman,1,2,11,* and Pasi A. Ja¨ nne2,3,4,9,11,*
1Massachusetts General Hospital Cancer Center, Boston, MA 02129, USA
2Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
3Lowe Center for Thoracic Oncology, Boston, MA 02115, USA
4Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA
5Guangdong Lung Cancer Institute and Cancer Center, Guangdong General Hospital, Guangzhou, China
6The Chinese University of Hong Kong, Hong Kong, China
7Department of Pathology, Brigham and Women’s Hospital, Boston, MA 02115, USA
8Pfizer Global Research and Development, Department of Research Pharmacology, La Jolla Laboratories, La Jolla, CA 92121, USA
9Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
10These authors contributed equally to this work
11These laboratories contributed equally to this work
*Correspondence: jengelman@partners.org (J.A.E.), pjanne@partners.org (P.A.J.)
DOI 10.1016/j.ccr.2009.11.022
SUMMARY
MET amplification activates ERBB3/PI3K/AKT signaling in EGFR mutant lung cancers and causes resistance
to EGFR kinase inhibitors. We demonstrate that MET activation by its ligand, HGF, also induces drug resistance,
but through GAB1 signaling. Using high-throughput FISH analyses in both cell lines and in patients
with lung cancer, we identify subpopulations of cells with MET amplification prior to drug exposure. Surprisingly,
HGF accelerates the development of MET amplification both in vitro and in vivo. EGFR kinase inhibitor
resistance, due to either MET amplification or autocrine HGF production, was cured in vivo by combined
EGFR and MET inhibition. These findings highlight the potential to prospectively identify treatment naive,
patients with EGFR-mutant lung cancer who will benefit from initial combination therapy.
INTRODUCTION
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors
(TKIs) gefitinib and erlotinib are effective clinical therapies for
patients with advanced non-small cell lung cancer (NSCLC) who
have EGFR-activating mutations (Asahina et al., 2006; Inoue
et al., 2006; Rosell et al., 2009; Sequist et al., 2008; Tamura
et al., 2008). A recent phase 3 clinical trial demonstrated that
patients with EGFR-mutant NSCLC had superior outcomes
with gefitinib treatment, compared with standard first-line cytotoxic
chemotherapy (Mok et al., 2009). However, despite these
dramatic benefits from EGFR TKIs in this genetically defined
cohort, all of these patients ultimately develop resistance
(referred to here as ‘‘acquired resistance’’) to gefitinib and erlotinib.
Two mechanisms of acquired resistance have been validated
in patients. Secondary mutations in EGFR itself, including
the EGFR T790M ‘‘gatekeeper’’ mutation is observed in 50% of
resistance cases, and amplification of the MET oncogene is
observed in 20% of resistance cases (Balak et al., 2006; Bean
et al., 2007; Engelman et al., 2007b; Kobayashi et al., 2005;
Kosaka et al., 2006; Pao et al., 2005). Both resistance mechanisms
lead to maintenance of ERBB3/PI3K/AKT signaling in
the presence of gefitinib (reviewed in Engelman and Janne,
2008).
SIGNIFICANCE
The therapeutic success of EGFR tyrosine kinase inhibitors (TKIs) in EGFR-mutant lung cancers is limited by the development
of drug resistance, mediated by MET amplification in a subset of patients. Here, we observe that MET amplification is
present in a small fraction of cells before drug exposure, and its emergence is dramatically accelerated by its ligand, HGF.
These findings provide insight into the origins of drug resistance in EGFR-mutant cancers and support a rationale for combination
treatment strategies as initial therapies, specifically in a molecularly defined cohort of patients with evidence of preexisting
MET amplification.
Cancer Cell