胃癌的精准治疗研究

张 俊

上海交通大学医学院附属瑞金医院肿瘤科

上海消化外科研究所

2019年7月12日 上海

胃癌的精准治疗研究

Top 10 Malignancies in Shanghai*

Rank1970’s1980’s1990’s2000’s2010’s(predict) 1Stomach Lung Lung Lung↔

2Lung Stomach Stomach colorectum↔

3Liver Liver colorectum Stomach↓

4Esophageal colorectum Liver Breast↑

5colorectum Breast Breast Liver↓

6Breast Esophageal Esophageal Pancrease↑

7uterine cervix Pancrease Pancrease Thyroid↑↑

8Leukemia Brain Brain Prostate↑↑

9Pancrease Bladder Bladder Brain↔

10Bladder Leukemia Gall-bladder Bladder↔

Pan K et al, Gut, 2016.

Cheung KS et al, Gut, 2018, 67:28–35.

Screening/Prevention

•The community-based intervention trial was launched in Linqu County, China.

• A total of 184 786 residents were enrolled and received 13C-urea breath test.

•The prevalence of H. pylori was 57.6%.

•H. pylori positive participants were assigned to either receiving a 10-day quadruple anti-H. pylori treatment or lookalike placebos

•

It gained an elimination of 72.9% of H. pylo ri in such community intervention trial without severe side effects among all the subjects during the entire

30-month trial period.

Long-term PPIs use was associated with a 2.4-fold increase in gastric cancer risk in H. pylori-infected subjects who had received

eradication therapy.

肿瘤地理学、病因干预与一级预防

TCGA胃癌分型系统：从表型到基因型的转化

亚型分类

基本特征

比例(%)

现有临床研究的靶点

EBV阳性

男性多见，好发于胃体及胃底

9

免疫检查点抗体JAK通路PIK3CA通路

MSI 女性多见，年龄偏大，好发于胃窦及幽门

22

免疫检查点抗体

GS 好发于年龄偏低者，弥漫型为主

20

RHOA信号通路

CIN 好发于胃食管交界处肠型为主

50

RTK扩增基因 （HER2, EGFR, MET, FGFR, VEGFA，PARP ）

Elevated PD-L1 & PD-L2 Expression in EBV+ Gastric Ca:

WJG，2018,24(18):1942

肿瘤细胞与微环境间的力学改建与适应

肿瘤微环境：

喜马拉雅还是温柔乡

100 m

药物输送 （Hoechst 33342, iv ）

血管 （CD31）

血管

应用血管生成抑制剂（2 周）

在应用血管生成抑制剂后药物输送出现增加（小鼠LLC 中的Hoechst 33342染色 ）

从器官特异性转移角度看胃癌腹膜转移 -- Rui Jin experience

Identified 27 mutated genes, of which 19 genes are

reported in COSMIC database (ZNF208, CRNN, ATXN3,

DCTN1, RP1L1, PRB4, PRB1, MUC4, HS6ST3, MUC17,

JAM2, ITGAD, IREB2, IQUB, CORO1B, CCDC121,

AKAP2, ACAN and ACADL), and 8 genes have not

previously been described in gastric cancer

(CCDC178, ARMC4, TUBB6, PLIN4, PKLR, PDZD2,

DMBT1and DAB1).

Additionally,GPX4 and MPND in 19q13.3-13.4 region,

is characterized as a novel fusion-gene.

Zhang J,et al. Science Rep, 2015,5,13750