改变前列腺癌的长期预后
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为什么这么小的腺体容易患癌症?
了解前列腺在人的一生中所扮演的角色有助于理解它为什么容易患癌症. The prostate is a gland within the male genitourinary system which, upon reaching puberty, 帮助产生精液，保护和滋养精子.4,5 This gland also produces prostate-specific antigen (PSA) to control sperm motility.6,7 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.8 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.5 The number of patients diagnosed with prostate cancer is increasing, 部分原因是由于人口老龄化和筛查的增加.9,10,11 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.10,11,12 在澳门葡京网赌游戏，澳门葡京赌博游戏致力于帮助改善前列腺癌患者的预后，澳门葡京赌博游戏的目标是支持在早期阶段识别这种疾病，以优化治疗方法的潜力.
时机决定一切——但为什么呢?
如果在疾病早期更容易治疗的阶段进行早期诊断，可以提高生存率. 当比较诊断后的存活率时, 早期(局部)诊断和晚期(晚期/转移性)诊断之间存在显著差异. The five-year survival rate for most patients with local prostate cancer is nearly 100%, 而对于晚期前列腺癌患者, 五年存活率下降到32%.13,14 通过争取早期诊断, we have a critical opportunity to reduce the chance of patients developing advanced disease, help them maintain a good quality of life and reduce the risk of morbidity.15
Prostate cancer is inherently sensitive to hormonal stimulation by male sex hormones. Therefore, being able to control hormone levels is of critical importance during treatment.16 Unfortunately, 前列腺癌可能对激素药物无反应，需要考虑其他治疗方案来控制疾病.17 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.18,19 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.16,20,21
什么是转移性去势抵抗性前列腺癌?
高达20%的晚期前列腺癌患者在确诊后约5年内会发展为去势抵抗性前列腺癌.22 转移性去势抵抗性前列腺癌(mCRPC)发生在前列腺癌生长并扩散到身体其他部位，并且对降低睾丸激素的治疗不再有效的时候. Most patients with mCRPC unfortunately succumb to this aggressive disease within two to three years, demonstrating the critical unmet need for therapy advancements in this area.23,24
人们已经认识到前列腺癌在生物学上是异质的，这意味着它们并不都是一样的.25 在治疗mCRPC的历史上, hormonal therapy has been used to control growth hormone levels, 化疗也是一种选择.23 科学研究表明，大约25%的mCRPC与DNA受损时涉及的关键修复机制相关的信号通路缺陷有关.26 通过确定基因组谱和评估与患者肿瘤相关的特定DNA修复基因的改变, 也许可以考虑新的治疗方法.27 其中一种潜在的靶向mCRPC治疗方法是PARP(多adp核糖聚合酶)抑制剂, 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
DDR和基因修复途径的作用
Every day, DNA strands in cells are repeatedly damaged and then repaired so they can function normally again. Many genes are involved in this DNA damage response (DDR) process – including BRCA1, BRCA2 and ATM.28,29,30 这些基因作为肿瘤抑制因子，是被称为“同源重组修复”(HRR)的修复途径之一的一部分。. Mutations in such genes result in impaired HRR and a compromised ability for the cell to repair its DNA. Mutations in other HRR genes (HRRm) can also influence cancer development. 通过高度针对性的方法, PARP inhibitors may be used to target the family of enzymes (PARPs) involved in DDR.27,30 By inhibiting their action, a cell must rely on alternative DNA repair pathways to survive. 以癌细胞为例, there are fewer functional pathways and the overwhelming level of DNA damage causes cell death.27,28,31
以了解有关DDR进程的更多信息, 修复途径中包含的蛋白质以及澳门葡京赌博游戏如何利用同源重组缺陷(HRD)中的缺陷, click here.
基因和生物标志物检测的重要性
To date, traditional approaches to treatments for advanced prostate cancer have been limited, 很少考虑肿瘤的基因组组成，以及它如何为治疗决策提供信息，以更好地个性化护理和改善结果.22,23
Genomic profiling or molecular testing can assess the presence of germline and somatic gene mutations. 种系突变是遗传性的，可以通过血液或唾液测试来识别，将样本与澳门葡京赌博游戏已知的基因组进行比较. 体细胞突变是在自然细胞分裂过程中获得的，或者是在人的一生中暴露于环境因素中获得的. As these somatic mutations will only be present in cells arising from the original mutated cell, 它们通常只在肿瘤形成后进行检测, by taking a tissue sample from the tumour and testing for gene alterations.32,33
检测DNA修复基因改变对于识别可能受益于靶向治疗方法的患者非常重要，对于临床预后和风险目的也很重要, 比如评估其他家庭成员的风险, or to assess an increased risk of other cancers associated with the same genetic profile.34
Our approach
The way we treat cancer is changing to a more ‘personalised’ targeted approach, 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.
Our commitment
提高对前列腺癌风险和症状的认识
Never Miss 是与MSD共同发起的一项旨在促进前列腺癌早期诊断的全球教育活动吗. 这一倡议解决了阻碍许多男性接受前列腺癌检查的个人障碍, while leveraging their passion for sports to capture their attention online. The campaign focuses on encouraging conversations between men and their loved ones, so that they would Never Miss 早期诊断的机会.
By engaging with men and their families via the multi-lingual website ProstateNeverMiss.com 并鼓励他们阅读更多的教育信息, 澳门葡京赌博游戏帮助澳门葡京赌博游戏的主要受众加深他们对前列腺癌风险和早期诊断重要性的认识.
References
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2. 世界卫生组织. IARC. Estimated number of incident cases from 2022 to 2050, Males, age [0-85+]. Available at: http://gco.iarc.fr /明天/ en / dataviz /趋势?types=0_1&sexes=1&mode=cancer&group_populations=0&multiple_populations=0&multiple_cancers=1&cancers=27&populations=900. Accessed May 2024.
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筹备日期:2024年5月