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1、肿瘤防治研究的新挑战,中国医学科学院,中国协和医科大学 肿瘤研究所 程书钧,我国恶性肿瘤发病及死亡情况的回顾与预测,预计在2020年，全球新发病例将达1500万(我国占1/5)，死亡1000万(我国占1/4)，现患病例3000万。,美国肿瘤学会2007年1月公布：美国2004年肿瘤死亡人数比2003年少3014人 (控烟、早诊筛查、治疗进步),人类控制肿瘤的关键,预防 控制癌前病变 肿瘤早期发现、诊断和治疗 对晚期肿瘤的合理治疗,控制癌前病变,癌变的多阶段发生模式,从正常细胞发展到危及生命的恶性肿瘤，大多经历“癌前病变”阶段。而从“癌前病变”发展成侵袭性癌一般需要10年或更长的时间，“癌前病变
2、”的一个重要特征是具有可逆性。,胃粘膜多阶段癌变过程,异型增生发生癌变的危险度增加41倍多；,1570%宫颈原位癌在10年后会发展成浸润癌；大约在3.54.5年中，16%的宫颈轻度不典型增生发展成重度不典型增生及原位癌。宫颈原位癌有30%或更高的机率会自行消退。,控制癌前病变,1950年以来，巴氏涂片检测宫颈癌前病变加上外科切除，使宫颈癌发生率和死亡率分别下降78和79，而未实施这项措施的国家,宫颈癌仍然是妇女肿瘤的主要死亡原因。,20mg/day (6682人) 对照(6706人) 69个月后 22/1000 43.4/1000 49岁下降44%; 50-59组降51%; 60组降55% 原
3、位癌组降56%;不典型增生组降86% Estrogen受体阳性组降69% Estrogen受体阴性肿瘤无明显影响 子宫内膜癌危险性上升 Stage1,Tamoxifen,Lung Cancer,The 54% regression rate of all preneoplastic lesions. 39% progression rate of severe dysplasia to CIS/SCC. 26% progression rate of lower-grade dysplasia to CIS/SCC. (Clinical Cancer Res. 2005, 11: 537-),
4、为什么有些癌前病变会发展成为浸袭性肺癌？而大部分不会？ 分子机制？(DNA, RNA, PROTEIN) 找到会发展成癌的癌前病变,肿瘤早期发现和诊断是肿瘤治疗的关键,美国、日本、中国胃癌患者手治疗术后5年生存率,肺癌 Stage 1病人5年生存率70%左右 Stage IV病人5年生存率5%左右,Low-dose CT筛查 31,567 无症状人群 (1993-2005)发现的 412 Stage 1肺癌病人10年生存率 88%, 302例病人在诊断后一个月做手术,10年生存率92%, 8例病人Stage 1,诊断后未接受治疗5年之内去世。 (N.Engl. J.Med. 2006, 355
5、: 1763-),未来肿瘤早诊研究趋势: 分子影像学 体液中肿瘤分子标志谱 临床: 高危人群筛查,肿瘤的不合理和过度治疗 值得认真反思 肿瘤的分子分型 和个体化冶疗,Breast cancer patients with the same stage can have markedly different treatment responses. The clinical behaviour (such as lymph node status and histological grade) fail to classify accurately outcome. Chemotherapy o
6、r hormonal therapy reduces distant metastases by one-third, however 70-80% of these patients would not developed distant metastases without the adjuvant treatment, these patients may not benefit from the treatment, and may potentially suffer from the side effects. (Nature, 2002,VOl.415, 530),FDA New
7、s FOR IMMEDIATE RELEASE P07-13 February 6, 2007 Media Inquiries: Karen Riley, 301-827-6242 Consumer Inquiries: 888-INFO-FDA FDA Clears Breast Cancer Specific Molecular Prognostic Test The U.S. Food and Drug Administration (FDA) today cleared for marketing a test that determines the likelihood of bre
8、ast cancer returning within five to 10 years after a womans initial cancer. It is the first cleared molecular test that profiles genetic activity. The MammaPrint test uses the latest in molecular technology to predict whether existing cancer will metastasize (spread to other parts of a patients body
9、). The test relies on microarray analysis, a powerful tool for simultaneously studying the patterns of behavior of large numbers of genes in biological specimens. The recurrence of cancer is partly dependent on the activation and suppression of certain genes located in the tumor. Prognostic tests li
10、ke the MammaPrint can measure the activity of these genes, and thus help physicians understand their patients odds of the cancer spreading. MammaPrint was developed by Agendia, a laboratory located in Amsterdam, Netherlands, where the product has been on the market since 2005. “Clearance of the Mamm
11、aPrint test marks a step forward in the initiative to bring molecular-based medicine into current practice,“ said Andrew C. von Eschenbach, M.D., Commissioner of Food and Drugs. “MammaPrint results will provide patients and physicians with more information about the prospects for the outcome of the
12、disease. This information will support treatment decisions. Agendia compared the genetic profiles of a large number of women suffering from breast cancer and identified a set of 70 genes whose activity confers information about the likelihood of tumor recurrence. The MammaPrint test measures the lev
13、el of activity of each of these genes in a sample of a womans surgically removed breast cancer tumor, then uses a specific formula, known as an algorithm, to produce a score that determines whether the patient is deemed low risk or high risk for spread of the cancer to another site. The result,弥漫性大B
14、-细胞淋巴瘤。(DLBCL)： 临床上发现病理上诊断为DLBCL病人存活时间有很大差异。 研究发现LM02，BCL6，FN1三个基因的 表达存活时间长，而CCND2，SCYA3， BCL2三个基因表达存活时间短。 （N.Engl, J.Med, 2004, 300: 1828- ）,癌旁组织基因芯片检测建立肝癌转移 分子预测模型,通过对伴有和不伴有门脉转移的肝癌患者癌周组织基因表达谱研究，发现伴有转移肝癌患者癌周肝组织的基因表达发生了显著改变。有两组基因表达差异尤其显著，而其中超过30是与炎症或免疫应答相关的基因。 Anti-inflammatory cytokines (Th2)such a
15、s IL4, IL5, IL8, and IL10 are highly elevated in livers with metastatic HCC. Pro-inflammatory cytokines(Th1) such as TL1A, TL1B, IL2, IFNG, TNF are significantly downregulated in livers with metastatic HCC.,用包含17个炎症或免疫应答相关基因建立分子预测模型预测95例肝癌患者的转移情况，结果对87例作出了是否转移的准确分类，准确率达92。 用这个预测模型对11例手术时不伴有转移而术后随访过程
16、中出现转移的6例肝癌患者作出了准确预测。 Cancer Cell 2006; 10: 99-111,42个基因可区分肺癌淋巴结转移,(50%),实现个体化治疗，避免过度治疗，是改善目前肿瘤治愈率低和死亡率高的有效途径。(本世纪 第一个十年末-2010将实现肿瘤个体化治疗) ( 高令巳有转移瘤病人 带瘤生存的整体综合治疗),肿 瘤 预 防,不吸烟: (吸烟者肺癌发病率是不吸烟者8-12倍) 与病毒相关的宫颈癌、肝癌将首先被控制 HPV病毒疫苗 化学药物预防（河南林县，Tamoxifen）,2006年6月9日美国FDA批准Gardasil (加德西)上市。5年随访发现该疫苗有 效预防了HPV16和HPV18型有关的宫 颈、外阴和阴道癌前病变发生。预防 HPV6 和 HPV11型相关的生殖器疣发 生。,US FDA New Molecular Entity (NME) Drug Approvals in Calendar Year 2006 Updated through December 31, 2006 NME New Dru
