引领胰腺癌的革命

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胰腺癌是第4位th 是西方国家和7个发达国家癌症死亡的主要原因th 全球癌症死亡的主要原因, 主要是由于其生物学和管理的复杂性.1,2,3 它也是所有“常见”癌症中存活率最低的癌症之一, with only 9% of patients with advanced (metastatic) disease surviving more than five years after diagnosis.4 Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer (accounting for 85% of cases)5, compared with pancreatic neuroendocrine tumours (PNETs) which are far less common and account for around 4% of cases.6

PDAC是最具侵袭性的癌症之一.7  Due to the diversity of genetic mutations and dense connective tissue that forms the pancreas, PDAC也是最耐化疗和耐辐射的癌症之一.1,8 PDAC has an extremely poor prognosis with only ~20% of patients surviving one-year at all stages of the disease.9 胰腺癌的病因仍不清楚, 尽管某些危险因素，比如吸烟, diabetes, 肥胖和慢性胰腺炎已被确认.2

多亏了专门的科学研究, 在更好地控制这种高发病率癌症方面已经取得了积极进展. 要理解为什么胰腺癌是如此复杂的挑战, we must first understand the crucial role that the pancreas plays in regulating bodily functions.  

胰腺——给身体带来平衡

扩大信息图表

胰腺本身是一个腺体器官，位于腹部，靠近肝脏. 胰腺在调节身体机能方面起着双重作用10,11:

  • 内分泌系统——胰腺分泌激素, 包括调节血糖的激素胰岛素和胰高血糖素, 直接进入血液
  • Exocrine system – the pancreas secretes enzymes into the digestive tract through a duct into the duodenum, 哪一个负责分解食物和吸收营养.

胰腺肿瘤

Pancreatic cancer is classified into two main tumour types – depending on whether the tumour forms in the exocrine cells, 或者内分泌细胞. 

PNETs, 俗称“胰岛细胞肿瘤”, 是一种罕见的在内分泌细胞中形成的癌症吗.12 PNETs 与更常见的癌症类型相比，有更好的预后.10

外分泌肿瘤占胰腺癌的96% 最常见的是PDAC.5,13 PDAC由排列在胰腺导管上的细胞发育而来. 这些导管输送消化液, 包含酶, 进入主胰管然后进入小肠的第一部分.9

As this disease has the potential to spread quickly and symptoms often do not present until the disease is at an advanced stage, more than 50% of pancreatic cancer patients are diagnosed when the disease has already spread to other organs in the body – for these patients the average survival is less 不到一年.5,14

这种疾病可能迅速传播有多种原因, 包括靠近胰腺的主要血管, 哪些容易被癌细胞入侵.15 因为PDAC症状是非特异性的, 诊断是非常有挑战性的, 这大大降低了存活的几率. 这导致PDAC被称为“沉默的杀手.’16

扩大信息图表

有限的治疗前景突出了迫切的未满足需求

从历史上看, patients with advanced pancreatic cancer have faced poor outcomes due to the aggressive nature of the disease and limited treatment advancements compared to other tumour types, 特别是在精准治疗方面落后于其他常见癌症.2,4,17,18

只有大约20%的晚期疾病患者有资格进行手术, 由于在诊断时癌症的转移(晚期)阶段, 而包括化疗和放疗在内的治疗选择往往有限.19,20 晚期胰腺癌的高症状负担提出了进一步的挑战, 因为症状会影响治疗效果和生活质量.21

胰腺癌——这种难治性疾病有可能是由生物标志物驱动的吗?

We have already come a long way in understanding what biomarker status means for cancers such as breast, prostate, ovarian, 肺和胃, 举几个例子. 随着基因组分析技术的出现, 选择性分子靶向治疗, biomarkers have now been shown to play an increasingly important role in the clinical management of pancreatic cancer patients.22

In PDAC, some tumour suppressor genes (which actively prevent the formation of cancer) are commonly mutated resulting in aggressive tumour growth.23 这些基因, 包括BRCA1/2, PRSS1和CDKN2A, 只是转移性胰腺癌的一些预测性生物标志物吗, and have uses far beyond diagnosis; they may also be used to predict potential treatment outcomes and help identify familial risk of developing PDAC.5,24

Targeted cancer therapies are drugs that interfere with specific molecules involved in cancer cell growth and survival. 了解靶向治疗是如何起作用的, 了解癌细胞的机制很重要.25

BRCA1/2基因构成DNA损伤反应(DDR)的一部分。, 或者是通过各种途径修复DNA损伤的过程. 当BRCA基因发生突变时, 阻碍DDR修复进程, 患癌症的风险也会增加.26 Around 5-10% of patients with familial PDAC and 3% of patients with sporadic PDAC are predicted to harbour a germline BRCA mutation. Knowing whether a patient carries this mutation may be used to help identify suitable treatment options.27

癌细胞的DNA损伤程度很高, 一个或多个DNA修复途径的缺失增加了DNA复制压力. 这些特性可以作为潜在的治疗靶点加以利用. 通过研究可以针对这些特定依赖关系的代理, treatments may actively target a fundamental feature of cancer cells and turn this against itself, 导致癌细胞死亡.27

有关利用癌症特异性ddr依赖性的更多信息 点击这里

胰腺癌研究和发展的未来

The prevalence of pancreatic cancer will continue to increase if we do not achieve further breakthroughs in diagnosis and treatment. Current strategies to improve treatment outcomes focus on earlier detection through screening and biomarker testing with more effective, 有针对性的治疗.28,29

BRCA-mutated metastatic pancreatic cancer is a devastating difficult-to-treat disease with critical unmet needs, 但随着基因检测的不断创新, 生物标志物的使用, 潜在的靶向治疗和持续的研究, 澳门第一赌城在线娱乐在帮助改变病人预后方面正在取得进展.30 AstraZeneca is committed to driving this progression and we strongly believe that to increase the pace at which progress is made in pancreatic cancer survival, 澳门第一赌城在线娱乐必须作为一个社区向前推进，帮助提高对未满足需求的认识, 在澳门第一赌城在线娱乐知道可以改进的地方激活改变.

参考文献

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