National Cancer Institute, Division of Cancer Prevention, Bethesda, MD 20892-7340, USA.
Semin Oncol. 2010 Jun;37(3):224-42. doi: 10.1053/j.seminoncol.2010.05.007.
A common belief is that the earlier that cancer is detected, the better the chance exists for reduced mortality and morbidity. The advent of new and emerging molecular, genetic, and imaging technologies has broadened the possible strategies for early detection and prevention, but a beneficial impact on mortality needs to be supported by clinical evidence. Molecular markers are being identified that are enhancing our ability to predict and detect cancer before it develops and at the earliest signs of impending carcinogenic transformation. Of the innumerable molecular markers in development, a standalone early detection marker with acceptable sensitivity and specificity is available for bladder cancer, although for most cancer sites there are promising avenues of research that will likely produce results in the next decade. The perfect molecular marker would be one that is inherently related to the disease, specifically to the processes of malignant tumorigenesis or to the defense mechanisms of the individual. For example, mutations associated with increased cancer risk often produce gene products that interfere with tumor-suppressor pathways (eg, DNA repair or cell-cycle control) or support oncogenic pathways (eg, through genetic instability or silencing the apoptotic pathway). Finding molecular markers associated with these processes, and where in the process they produce their actions, can lead to interventions based on maintaining support for the normal process and interrupting the action of the products of the mutation. The search for molecular markers for cancer prevention and early detection presents a formidable challenge that requires a systematic and scientifically sound validation process. The search encompasses a broad range of scientific disciplines, including biochemistry, genetics, histology, immunology, informatic technologies, and epidemiology; strategies to identify and understand molecular markers are approached with multidisciplinary teams focused on understanding the mechanistic basis of cancer and the processes and pathways that underlie carcinogenesis.
人们普遍认为，癌症越早被发现，降低死亡率和发病率的机会就越大。新出现的分子、遗传和成像技术拓宽了早期检测和预防的可能策略，但需要临床证据来支持对死亡率的有益影响。人们正在确定分子标记物，以增强我们在癌症发展之前以及在致癌转化的最早迹象时预测和检测癌症的能力。在众多正在开发的分子标记物中，有一个用于膀胱癌的具有可接受敏感性和特异性的独立早期检测标记物，尽管对于大多数癌症部位，都有很有前途的研究途径可能会在未来十年内产生结果。理想的分子标记物应该与疾病本身、与恶性肿瘤发生过程或个体的防御机制密切相关。例如，与癌症风险增加相关的突变通常会产生干扰肿瘤抑制途径（例如，DNA 修复或细胞周期控制）或支持致癌途径（例如，通过遗传不稳定性或沉默凋亡途径）的基因产物。寻找与这些过程相关的分子标记物，以及它们在哪个过程中产生作用，可以导致基于维持正常过程的支持和中断突变产物的作用的干预。癌症预防和早期检测的分子标记物的寻找提出了一个艰巨的挑战，需要一个系统和科学合理的验证过程。该研究涵盖了广泛的科学学科，包括生物化学、遗传学、组织学、免疫学、信息学技术和流行病学；识别和理解分子标记物的策略是由专注于理解癌症的机制基础以及致癌发生的过程和途径的多学科团队来进行的。
