肿瘤份防治与思考

乳腺癌发现1,137个基因突变, 大肠癌848个基因突变 A few gene ‘mountains’ are mutated in a large proportion of tumors; Most genes are mutated in <5% of
tumors represented as ‘hills
• The driver genes are much more highly connected and enriched in protein complex (hubs within an interaction network)(these genes are longer)
• Cancer genome is shaped through a process of cumulative haploinsufficiency and triplosensitivity
Driver genes can be classified into 12 signaling pathways that regulate three core cellular processes: cell fate, cell survival, and genome maintenance.
• 2010年作为中国区的中心实验室，组织全 国18家医院进行了亚裔肺腺癌患者EGFR基 因突变状态的分子流行病学（PIONEER）研 究，有7个国家或地区（中国大陆、中国香
港、印度、菲律宾、中国台湾、泰国和越 南）的51个研究中心提供了1450例肺癌患 者组织样本进行EGFR基因突变分析，本实
验室完成了741例样本检测（突变率51.1%)
个体化诊治的进展与挑战
Timeline related to cancer treatment
• 乳房切除(mastectomy 1894) • 头颈癌放射治疗(1928) • 淋巴瘤氮芥治疗(1943) • 免疫治疗(Interlukin-2,1985) • 靶向治疗(CML 1996) • 单抗治疗(rituximab 利妥昔B-cell lymphoma
To date, these studies have revealed ~140 genes that,when altered by intragenic mutations, can promote or “drive” tumorigenesis.
A typical tumor contains two to eight of these “driver gene” mutations; the remaining mutations are passengers that confer no selective growth advantage.
1997)
靶向药物
Glivec 慢性粒细胞白血病 Bcr-abl酪氨酸激酶抑制剂 几乎
所有的CML均有异常的融合蛋白Bcr-abl的表达，因此针对此 融合蛋白的靶向药物Glivec，抗肿瘤特异性非常高。
类别 所有部位
肺癌 胃癌 肝癌 食管癌 结直肠癌 女性乳腺癌 白血病 脑瘤 膀胱癌 胰腺癌 恶性淋巴瘤 鼻咽癌
新病例 2817210
522050 464439 402208 259235 221313 169452
70826 66454 54927 44217 43525 33101
WHO/IARC: GLOBCAN 2008
• Any individual gene functions as a tumor suppressor or oncogene.Many more genes possess cancer driver properties than anticipated forming a continuum of oncogene potential.
类别 所有部位
肺癌 肝癌 胃癌 食管癌 结直肠癌 白血病 脑瘤 女性乳腺癌 胰腺癌 宫颈癌 恶性淋巴瘤 鼻咽癌
死亡病例 1958347
452813 372079 352315 211084 110486
54606 45573 44908 39817 33914 25166 20899
Cancer. Online Dec. 16, 2013. DOI: 10.1002/cncr.28509. Online at www.wileyonlinelibrary.com/journal/cancer-report2014
Timeline related to cancer research
• 肿瘤与胚胎发育遵循同样的调控规律 (Rudolf Virchow 1858)
• 肿廇染色体改变(Boveri 1914, Ph1 1960) • 癌基因(Bishop and Varrmus 1976) • 抑癌基因(RB 1987) • 人类基因测序(2003) • 肿瘤外显子测序(2006) • 肿瘤全基因组测序(2008)
’两个个体肿瘤之间突变基因重复的很少， (Science 2007,318: 1108)
29 MARCH 2013 VOL 339 SCIENCE
For most cancer types, this landscape consists of a small number of “mountains” (genes altered in a high percentage of tumors) and a much larger number of “hills” (genes altered infrequently).
肺癌防治研究的新思考
中国医学科学院，北京协和医学院 肿瘤研究所/医院
分子肿瘤学囯家重点实验室 程书钧
上世纪70年代全国8.5亿人口调查
每年约70万人死于癌症
前5位
%
• 胃癌 24.0
• 食管癌 23.5
• 肝癌 19.7
• 宫颈癌 18.4
• 肺癌 5.5
ቤተ መጻሕፍቲ ባይዱ
全国死因调查
我国癌症年新病例和死亡病例数