改变前列腺癌的长期预后

前列腺癌是男性中第二常见的癌症^* 它是全球癌症死亡的第五大原因，发病率为1%.到2020年，全球将有37.5万人死亡.^1,2
 
尽管可用的治疗方法有所增加, 问题并没有消失, with the number of patients predicted to die from prostate cancer expected to almost double over the next 20 years.^1,2,3,4 At AstraZeneca our aim is to help improve the lives of these patients with the ambition to one day help eliminate prostate cancer as a cause of death.

Understanding the role of the prostate throughout someone’s life helps to understand why it is vulnerable to cancer. 前列腺是男性泌尿生殖系统中的一个腺体, 进入青春期后, 帮助产生精液，保护和滋养精子.^5,6 这个腺体也产生前列腺特异性抗原(PSA)来控制精子的活力.^7,8 随着更多的生长激素睾丸激素的产生, 前列腺随着年龄的增长而逐渐增大并继续增长.⁹ 虽然这最初是正常过程的一部分, 如果这种增长变得无法控制, cancer can form.⁶ 被诊断为前列腺癌的患者数量正在增加, 部分原因是由于人口老龄化和筛查的增加.¹ 许多患者表现为早期(局部)前列腺癌, but approximately 20-30% will unfortunately see their disease progress to advanced (metastatic) disease.^,9,10,11,12 At AstraZeneca we are dedicated to helping improve the outcomes for patients affected by prostate cancer and our aim is to support the identification of this disease at the earliest stages in order to optimise the potential of therapeutic approaches.

Early diagnosis can lead to benefits in survival if made when the disease is at an early more treatable stage. 当比较诊断后的存活率时, there is a significant difference between an early (localised) diagnosis and a late (advanced/metastatic) diagnosis. 大多数局部前列腺癌患者的五年生存率接近100%, 而对于晚期前列腺癌患者, 五年存活率下降到31%.^6,13 通过争取早期诊断, 澳门第一赌城在线娱乐有一个关键的机会来减少患者发展为晚期疾病的机会, 帮助他们维持良好的生活质量，降低发病风险.¹

前列腺癌天生对男性性激素的激素刺激敏感. 因此，能够控制激素水平在治疗过程中是至关重要的.¹⁴ Unfortunately, prostate cancer can become unresponsive to hormonal agents and alternative treatment options need to be considered to control the disease.¹⁵ 如果癌症对治疗产生抗药性, 局部可能进一步恶化, 并扩散到身体的其他部位.^16,17,18 在疾病的这个阶段, 控制症状很重要, 延缓疾病进展, 尽可能延长生命.^19,20,21

Approximately 10-20% of patients with advanced prostate cancer will develop castration-resistant prostate cancer within approximately 5 years of diagnosis.²² Metastatic castration-resistant prostate cancer (mCRPC) occurs when prostate cancer grows and spreads to other parts of the body and no longer responds effectively to testosterone-lowering treatments. 大多数mCRPC患者不幸在两到三年内死于这种侵袭性疾病, 展示了该领域治疗进步的关键未满足需求.^23,24

Prostate cancers have been recognised to be biologically heterogeneous – meaning that they are not all the same.²⁵ 在治疗mCRPC的历史上, 激素疗法已被用于控制生长激素水平, 化疗也是一种选择.^23,22, Scientific studies have shown that approximately 25% of mCRPC is associated with defects of the signalling pathway associated with the key repair mechanisms involved when DNA is damaged.²⁶ By determining the genomic profile and assessing the alteration of specific DNA repair genes associated with a patient’s tumour, 也许可以考虑新的治疗方法.²⁸ One such approach and class of potential targeted mCRPC therapies are PARP (poly-ADP ribose polymerase) inhibitors, 阻断DNA修复蛋白PARP的活性. 而“健康”细胞需要PARP来修复DNA损伤, 它可以在癌细胞中被PARP抑制剂破坏, 阻止DNA修复并导致细胞死亡.^27,28

Every day, 细胞中的DNA链被反复破坏，然后被修复，这样它们就能再次正常工作. 许多基因参与这种DNA损伤反应(DDR)过程，包括BRCA1、BRCA2和ATM.^28,29 These genes act as tumour suppressors and are part of one of the repair pathways known as ‘homologous recombination repair’ (HRR). Mutations in such genes result in impaired HRR and a compromised ability for the cell to repair its DNA. 其他HRR基因(HRRm)的突变也会影响癌症的发展. 通过高度针对性的方法, PARP抑制剂可用于靶向参与DDR的酶家族(PARP).³⁰ 通过抑制它们的作用，细胞必须依靠替代的DNA修复途径来生存. 以癌细胞为例, 有更少的功能途径和压倒性的DNA损伤水平导致细胞死亡.³¹

以了解有关DDR进程的更多信息, the proteins included in the repair pathway and how we can exploit deficiencies in homologous recombination deficiency (HRD), click here.
 

To date, 治疗晚期前列腺癌的传统方法受到限制, with little consideration given to the genomic make-up of the tumour and how it could inform treatment decisions to better personalise care and improve outcomes.^32,33

基因组分析或分子检测可以评估种系和体细胞基因突变的存在. A germline mutation is hereditary and can be identified using a blood or saliva test to compare the sample against our known genome. Somatic mutations are acquired during natural cell division or from exposure to environmental factors throughout someone’s life. 因为这些体细胞突变只会出现在由原始突变细胞产生的细胞中, 它们通常只在肿瘤形成后进行检测, 通过从肿瘤中提取组织样本并检测基因变化.^32,34

Testing for DNA repair gene alterations is important to identify patients who may benefit from targeted treatment approaches and is clinically important for prognostic and risk purposes, 比如评估其他家庭成员的风险, 或者评估与相同基因图谱相关的其他癌症的风险增加.³⁵

澳门第一赌城在线娱乐治疗癌症的方式正在转变为一种更加“个性化”的有针对性的方法, 前列腺癌也不例外. 而基因突变加剧了癌症的发展, they can also help us to understand and exploit deficiencies in the repair pathways of certain cancers

At AstraZeneca we remain wholly committed to innovative research that allows us to build on our long-standing oncology history and help as many patients living with prostate cancer as possible.

澳门第一赌城在线娱乐将继续研究针对mCRPC患者的个性化治疗方案, 正如澳门第一赌城在线娱乐在卵巢中看到的, 乳腺癌和胰腺癌, 所以澳门第一赌城在线娱乐有一天可以实现澳门第一赌城在线娱乐的目标，消除前列腺癌作为死亡原因.

Reference

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