确定肝癌的新靶点

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The liver performs numerous vital functions including filtering the body’s blood supply and – as a key organ of the immune and circulatory systems – contains numerous immune cells that defend the body against blood-borne pathogens and aid in wound healing.1,2,3,4 In addition, 肝脏是再生的, meaning it can replace damaged tissue by regrowing its existing tissue – up to two-thirds of its total size.5,6,7 The unique pathogen-clearing and wound-healing properties of the liver require that resident immune cells are often active and ready to protect the body from harm.3,4 作为保护身体能力的一部分, 肝免疫细胞通常也能够检测到异常的细胞, 在它们分裂并长成危险的肿瘤之前攻击并移除它们.3,8 This state of immune readiness is a critical way liver immune cells are able to rapidly respond to pathogens and injury.9

慢性炎症——肝脏的“致命弱点”

炎症是免疫系统对威胁的标准反应的自然组成部分.9 Ordinarily, 炎症是急性的, 或者短期的, 一旦病原体被清除或伤口愈合就会结束.9 但在某些情况下，炎症反应会持续存在.10 Liver damage from hepatitis virus infection or as a result of excessive and prolonged alcohol intake can lead to chronic inflammation that ultimately may interfere with the typical ability of liver immune cells to attack and remove abnormal cells.10,11 当免疫细胞以这种方式受到阻碍时，澳门葡京赌博游戏称之为免疫抑制.12 不幸的是，肝脏的免疫抑制甚至会在损伤期后持续.5 免疫细胞攻击和清除异常细胞的能力减弱, 肝脏中的细胞更容易癌变.11 Removing immunosuppression and restoring the ability of immune cells to attack and remove abnormal cells may be a key way to manage cancers that arise in the liver.11,13

*该数据代表肝细胞癌和肝内胆管癌

肝癌的发病率仍在上升

几十年来，全球肝癌病例数持续上升.14 2020年，肝癌是所有癌症相关死亡的第三大常见原因.15* 肝细胞癌(HCC)是成人中最常见的肝癌, 约占所有原发性肝癌病例的75%.16,17

为什么肝癌如此普遍?

80%到90%的HCC病例是肝硬化的结果, 其中最常见的是乙型或丙型肝炎病毒感染.17 这些病毒分布广泛，难以控制, 特别是在世界上许多发展中国家, 使得减轻HCC的全球负担变得困难.18,19 世界上超过72%的HCC病例发生在这些病毒流行的亚洲.20-22 仅中国就占所有新诊断肝癌病例和死亡病例的一半以上, 尽管人口还不到世界的20%.23

Ongoing programs focused on prevention and screening of hepatitis are important to reduce the number of new HCC cases.17,18,19 However, there remains an urgent need for research that will provide more effective treatment options for patients with HCC than what is available today.24

Treating HCC

HCC筛查具有挑战性.25 虽然早期发现是目标, 大多数体征和症状出现在HCC晚期, 早期肿瘤通常很难在体检中发现.25 As such, 大多数患者在治疗选择有限的疾病晚期才被诊断出来.25

HCC是根据巴塞罗那临床肝癌(BCLC)系统进行分期的, 由于疾病阶段决定了患者可用的选择:26

Treatment for early stage (Stage 0 to A) disease and intermediate stage (Stage B) disease may involve:27,28

  • Surgery 切除肿瘤.

  • 肝脏移植手术 可能对一些早期疾病的患者有根治性治疗吗.

  • 热消融(也称为射频消融或微波治疗) 在疾病的早期阶段，利用热量摧毁病人体内的癌细胞.

  • 经动脉化疗栓塞，或TACE is used to treat early- and intermediate-stage tumours that cannot be treated with surgery or thermal ablation. 在手术过程中, 医生将化疗直接注入动脉, 然后阻断哪一个以增加肿瘤对药物的暴露.

中期(B期)和晚期(C期)疾病的治疗可能包括:29

  • 系统性治疗 is used in Stage B patients who are ineligible for other treatments or progressed on other therapies, 以及C期患者. There is a critical unmet medical need for new treatments that can treat patients with advanced stages of HCC. 正在进行的研究表明，免疫肿瘤疗法在这种具有挑战性的环境中显示出希望.

Our approach

Pioneering new research has deepened our understanding of the processes leading to the immunosuppression involved in liver cancer.13 Mounting evidence has shown that reversing immunosuppression may restore the ability of immune cells to attack and remove cancer cells, 可能减缓肿瘤生长或缩小的.30

逆转免疫抑制的治疗被称为免疫疗法, 现在有多种免疫疗法可能导致抗肿瘤活性.30,31 Our goal is to explore immunotherapy combinations for overcoming the drivers of immunosuppression involved in liver cancer, 目的是改善肝癌患者的生存状况.


这些努力继续建立在澳门葡京赌博游戏多样化的实践改变结果的基础上, 免疫肿瘤学临床方案在多个, 固体肿瘤, and we remain committed to harnessing the versatile power of immunotherapy and immunotherapy combinations to redefine cancer care.

澳门葡京赌博游戏的科学平台

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在澳门葡京网赌游戏, 澳门葡京赌博游戏以创新为动力，致力于为患者的生活带来真正的改变. 加入澳门葡京赌博游戏，帮助提供改变生活的药物. Be among our employees who continue to make us an innovation-driven company that stands firmly among the world’s leaders in biopharmaceuticals. 
 

澳门葡京网赌游戏的职业

Our people

"I believe personalised healthcare is the future of medicine; it allows us to use the latest diagnostic science to target medicines to patients most likely to benefit." Ruth March，精密医学高级副总裁，R&D Oncology

查看Ruth的个人资料
苏珊·加尔布雷斯

肿瘤学执行副总裁&D
马克·奥康纳

早期肿瘤发现首席科学家
Ti Hwei How

国际肿瘤学副总裁

References

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2. Cullen JM, et al. 肝脏和胆道系统. Jubb,肯尼迪 & 帕尔默家畜病理学. 2016;2:258‐352.e1.

3. Endig J et al. 适应性免疫系统在肝损伤和肝癌发展中的双重作用. Cancer Cell. 2016;30(2):308-323.

4. Krzyszczyk P, et al. The Role of Macrophages in Acute and Chronic Wound Healing and Interventions to Promote Pro-wound Healing Phenotypes. Front Physiol. 2018;9:419.

5. Markose D, et al. 肝脏再生和修复的免疫细胞调控. [J]免疫再生医学. 2018;2:1-10.

6. Kwon YJ, et al. 肝再生进展的临床意义. 临床Mol肝醇. 2015;21(1):7-13.

7. Michalopoulos GK. 肝再生. J细胞生理学. 2007;213(2):286-300.

8. Eggert T, et al. 肿瘤对肝脏组织环境的调节. 杂志. 2017;173:47‐57.

9. Robinson M, et al. 肝脏免疫学及其在炎症和体内平衡中的作用. Cell Mol Immunol. 2016;13:267-276.

10. Tanaka M, et al. 炎症后肝脏再生和纤维化. Inflamm回复. 2016;36:19.

11. Kubes P, et al. 肝脏的免疫反应. Annu Rev immuno1. 2018;36:247-277.

12. Han Y, et al. Human CD14+ CTLA-4+ Regulatory Dendritic Cells Suppress T-Cell Response by Cytotoxic T-Lymphocyte Antigen-4-Dependent IL-10 and Indoleamine-2,肝细胞癌中3-双加氧酶的产生. Hepatology. 2014;59(2):567-579.

13. Lu C, et al. Current Perspectives on the Immunosuppressive Tumor Microenvironment in Hepatocellular Carcinoma: Challenges and Opportunities. Mol Cancer. 2019;18:130.

14. Altekruse科幻, et al. 美国不断变化的肝细胞癌发病率和肝癌死亡率. 我是胃肠醇吗. 2014;109(4):542‐553.

15. 世卫组织国际癌症研究机构. World. 可在:http://gco.iarc.fr /今天/数据/资料/数量/ 900 -世界-事实表.pdf. 2022年5月访问.

16. ASCO. 肝癌:简介. 可在:http://www.cancer.net/cancer-types/liver-cancer/intro-duction. 2022年5月访问.

17. Li D, et al. Current Treatment Landscape for Advanced Hepatocellular Carcinoma: Patient Outcomes and the Impact on Quality of Life. 癌症(巴塞尔). 2019;11(6):841.

18. Zampino R, et al. 发展中国家乙型肝炎病毒负担. 世界J胃肠醇. 2015;21(42):11941‐11953.

19. Averhoff FM, et al. 全球丙型肝炎负担:美国医疗保健提供者的考虑. 临床感染与疾病. 2012;科学通报1:518 - 518.

20. Singal AG, et al. 肝细胞癌的流行病学和监测:新趋势. J Hepatol. 2020;72(2):250-261.

21. Petruzziello, et al. Global Epidemiology of Hepatitis C Virus Infection: An Up-Date of the Distribution and Circulation of Hepatitis C Virus Genotypes. 世界J胃肠醇. 2016;22(34):7824‐7840.

22. Shan S, et al. 如何控制亚洲高地方性乙型肝炎. Liver Int. 科学通报，2018;38(增刊):122‐125.

23. Zheng R, et al. 中国肝癌发病率和死亡率:到2030年的时间趋势和预测. 中国癌症研究所. 2018;30(6):571‐579.

24. Bupathi M, et al. 肝细胞癌:哪里有未满足的需求. 分子肿瘤学. 2015;9(8):1501-1509.

25. 美国癌症协会. 肝癌能早发现吗? 可在:http://www.cancer.org/cancer/liver-cancer/detection-diagnosis-staging/detection.html. 2022年5月访问.

26. 英国癌症研究中心. BCLC分期系统和Child-Pugh系统. 可在:http://www.cancerresearchuk.org/about-cancer/liver-cancer/stages/bclc-staging-system-child-pugh-system. 2022年5月访问.

27. Vogel A, et al. Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. 肿瘤学年鉴. 2018; 29 (4): IV238-IV255.

28. ASCO. 肝癌的栓塞治疗. 可在:http://www.cancer.org/cancer/liver-cancer/treating/embolization-therapy.html. 2022年5月访问. 

29. Kim E和Viatour P. 肝细胞癌:老朋友和新把戏. Experimental & 分子医学. 2020;52:1898-1907. 

30. Joshi S, et al. Combinatorial Approach to Improve Cancer Immunotherapy: Rational Drug Design Strategy to Simultaneously Hit Multiple Targets to Kill Tumor Cells and to Activate the Immune System. J Oncol. 2019;2019:5245034.

31. 国家癌症研究所. 免疫疗法治疗癌症. 可在:http://www.cancer.gov /对癌症治疗/类型/免疫疗法. 2022年5月访问.

Veeva ID: Z4-42953
筹备日期:2022年5月