2015 Aug % HER2 8% ~ 40% HER3 35% ~ 100% EGFR HER EGFR Kiyose 5 FISH EGFR 4. 9% EGFR Cetuximab 2 VEGF EGFR EGFR II Lordick ~
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1 950 CN /R ISSN http / /www. cjcpt. com 2015 Aug EGFR 2 HER2 VEGF PI3K / mtor C-Met - PARP FGFR FGFR-1 MK-866 Rilotumumab Olaparib 2014 ASCO Ⅲ Ramucirumab 3 " " PI3K /mtor R45 A Tel chenshuhui2008@ 126. com Tel wangguihua5708@ 163. com 1 1 HERS HERS HER EGFR HER1 HER2 HER3 HER4 EGFR 33% ~
2 2015 Aug % HER2 8% ~ 40% HER3 35% ~ 100% EGFR HER EGFR Kiyose 5 FISH EGFR 4. 9% EGFR Cetuximab 2 VEGF EGFR EGFR II Lordick ~ 4 15% 14% % 79% VEGF Ⅲ 2012 EMSO ASCO FDA ACRC HER-2 OS NSCLC 2010 ASCO PFS HER % ~ 23% HER2 XP HER2 OS HR = % Cl HER ~ P = HER2 PFS HER2 9 RR PFS HER P = trastuzumab % 37% P = HER2 HER HER2 3 EGFR HER2 HER2 12 Bevacizumab VEGF HER2 Ⅲ AVAGAST Apatinib pertuzumab HER2 - HER2 2 VEGFR-2 VEGFR-2 ATP 10 lapatinib II 2013 JCO EGFR /HER III 16 HER2 EGFR ORR EGFR 2. 84% 0. 00%
3 952 Chin J Clin Pharmacol Ther 2015 Aug 20 8 mos 195 d vs 140 d HR = % CI ~ P < mpfs 3 PI3K /mtor 78 d 53 d HR = % CI ~ P < PI3K 2% 3 /4 PI3K Ramucirumab VEGFR2 IgG1 KDR /VEGFR2 VEGFR2 PI3K VEGFR2 PI3K Ramucirumab 17 LY III 29 mtor mtor ramucirumab 117 mtor mtor 5. 2 vs 3. 8 HR = % Cl ~ P = PFS 779 Temsirolimus Sirolimus FDA Lily RAD001 Everolimus AP VEGFR2 ramucirumab de-forolimus MK III ramucirumab Ohtsu 24 Ⅲ ramucirumab ramucirumab + BSC % Cl 8. 5 ~ % CI 6. 3 ~ % Cl ~ P = PI3K 20 PI3K RTE /PI3K /Akt Xu 21 CCI- I OS 5. 4 VEGF HR = % Cl = ~ P = PFS vs
4 2015 Aug HR = % Cl = ~ P < PFS 2014 ASCO Ⅲ PI3K Ramucirumab PI3K /mtor 4 C-Met C-Met /HGF / Rilotumumab HGF " " HGF C-Met Ⅱ Rilotumumab ECx ECx / OS PFS C-Met Rilotumumab Rilotumumab ECx Jemal AF Bray F Center MM et a1. Global cancer statistics J. CA Cancer J Clin Siegel R Naishadham D Jemal A. Cancer satatistics 2012 J. CA Cancer J Clin AZD FGFR-2 3 Weinstein IB Joe AK. Mechanisms of disease oncogene addiction-a rationale for molecular targeting DNA in - PARP Olaparib Ⅱ M. 2. Olaparib -1 IGF-1R 28 MMP HDAC COX Aurora 90 HSP90 30 cancer therapy J. Nat Clin Pract Oncol Kiyose S Nagura K Tao H et al. Detection of kinase amplifications in gastric cancer archives using fluorescence in situ hybridization J. Pathol Int Moehler M Mueller A Trarbach T et al. Cetuximab with irinotecan folinic acid and 5-fluorouracil as firstline treatment in advancedgastroesophageal cancer a prospective multi-center biomarker-oriented phase II study J. Ann Oncol Lordick F Kang YK Chung HC et al. Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer EXPAND a randomised open-label phase 3 trial 5 J. Lancet Oncol Bang YJ Van Cutsem E Feyereislova A et al. Trastuzumab in combination with Chemotherapy versus chemotherapy alone for treatment of HER2-positiveadvanced gastric or gastro-oesophageal junction cancer
5 954 Chin J Clin Pharmacol Ther 2015 Aug 20 8 ToGA a phase 3 open-label randomised controlled trial J. Lancet Gravalos C Jimeno A. HER2 in gastric cancer a new prognostic factor and a novel therapeutic target J. Ann Oncol Yamashita-Kashima Y Shu S Harada N et al. Enhanced antitumor activity of trastuzumab emtansine T- DM1 in combination with pertuzumab in a HER2-positive gastric cancer model J. Oncol Rep Oshima Y Tanaka H Murakami H et al. Lapatinib sensitivities of two novel trastuzumab-resistant HER2 gene-amplified gastric cancer cell lines J. Gastric Cancer Pazo Cid RA Antón A. Advanced HER2-positive gastric cancer current and future targeted therapies J. Crit Rev Oncol Hematol Okines AF Reynolds AR Cunningham D. Targeting angiogenesis in esophagogastric adenocarcinoma J. Oncologist Ohtsu A Shah MA Van Cutsem E et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer a randomized double-blind placebo-controlled phase III study J. J Clin Oncol Li J Qin S Xu J Guo W et al. Apatinib for chemotherapy-refractory advanced metastatic gastric cancer results from a randomized placebo-controlled parallel-arm phase II trial J. J Clin Oncol Shukui Qin. Phase III study of apatinib in advanced gastric cancer A randomized double-blind placebocontrolled trial C ASCO Annual Meeting. USA Chicago Fuchs CS Tomasek J Yong CJ et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma RE- GARD an international randomised multicentre placebo-controlled phase 3 trial J. Lancet Wilke H Muro K Van Cutsem E et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma RAIN- BOW a double-blind randomised phase 3 tria J l. Lancet Oncol Javle M Smyth EC Chau I. Ramucirumab successfully targeting angiogenesis in gastric cancer J. Clin Cancer Res Vivanco I Sawyers CL. The phosphatidylinositol 3-kinase-AKT pathway in human cancer J. Nature Reviews Cancer Lennerz JK Kwak EL Ackerman A et al. MET amplification identifies a small and aggressive subgroup of esophagogastric adenocarcinoma with evidence of responsiveness to crizotinib J. J Clin Oncol Efeyan A Sabatini DM. mtor and cancer many loops in one pathway J. Curr Opin Cell Biol Faden B Friese-Hamim M et al. EMD and EMD constitute a new class of potent and highly selective c-met inhibitors J. Clin Cancer Res Ohtsu A Ajani JA Bai YX et al. Everolimus for previously treated advanced gastric cancer results of the randomized double-blind phase III GRANITE-1 study J. J Clin Oncol Oliner Ks Tang R Anderson A et a1. Evaluation of MET pathway biomarkers in a phaseⅡstudy of rilotumumab R AMG102 or placebo P in combination with epirubicin cisplatin and capecitabine ECX in patients pts with locally advanced or metastatic gastric G or esophagogastric junction EGJ cancer J. Clin Oncol Suppl a Xie L Su X Zhang L et al. FGFR2 gene amplification in gastric cancer predicts sensitivity to the selective FGFR inhibitor AZD4547 J. Clin Cancer Res Bang YJ Im SA Lee KW et al. Olaparib plus paclitaxel in patients with recurrent or metastatic gastric cancer a randomized double-blind phaseⅡstudy J. J Clin Oncol 2013 Suppl a Li H Adachi Y Yamamoto H et al. Insulin-like growth factor-i receptor blockade reduces tumor angiogenesis and enhances the effects ofbevacizumab for a human gastric cancer cell line MKN45 J. Cancer J J
6 2015 Aug Advances of target therapy for gastric cancer CHEN Shu-hui YANG Fan-fan HE Jun ZHOU Peng WANG Gui-hua Department of Oncology Changsha Central Hospital Changsha Hunan China ABSTRACT Chemotherapy is mainly used in the treatment for advanced gastric cancer. However therapy of cytotoxic drug combination has poor specificity in killing tumor cells and normal cells so there are clear side effects in traditional chemotherapy. This paper reviews gastric cancer related factors and the advances of target therapy for gastric cancer factors include EGFR HER2 VEGF PI3K / mtor C-Met PARP FGFR FGFR-1 and so on. Researchers have developed many molecular targeted drugs in clinic Cetuximab Apatinib Ramucirumab trastuzumab lapatinib pertuzumab bevacizumab rapamycin sirolimus everolimus MK-866 Rilotumumab Olaparib and so on. These targeted drugs play a role against tumor-specific markers with the advantage of specificity and fewer side effects. In view of good efficacy these drugs will provide a new treatment program for patients with anti-tumor " individual treatment". KEY WORDS gastric cancer target therapy HERS VEGF PI3K /mtor 櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂櫂 mm 205 mm 120 CN /R ISSN CSCD Q cjcpt96@ 163. com http / /www. cjcpt. com
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