Greenwald P, Witkin K M, Malone W F, Byar D P, Freedman L S, Stern H R
Division of Cancer Prevention and Control, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Int J Cancer. 1992 Sep 9;52(2):189-96. doi: 10.1002/ijc.2910520206.
Biological markers may provide a valuable tool for the development of cancer prevention agents, for monitoring patient compliance to a selected intervention, or for further defining the carcinogenic process. This discussion focuses on markers of biological effect and the rationale for their use in cancer prevention trials. Recent studies with biological markers are investigating their incorporation into phase-I, -II, and -III chemoprevention clinical trial designs. Their use in clinical studies is expected to increase the number of agents that may be evaluated and to provide valuable information on the biological effectiveness of agents, doses, and schedules. Markers may also provide information to help in selecting high-risk groups for prevention research, and to indicate the pathways inhibited and the stage of carcinogenesis affected. Such information may prove of crucial importance in strengthening the rationale for long-term trials and other ancillary research. Biomarker research for colon carcinogenesis is discussed, including examples of a number of recent trials that may influence future progress in this area of prevention research. A crucial step in this process is marker validation as an aspect of major prospective observational and intervention studies where cancer incidence is the endpoint. We cannot be fully confident of markers as intermediate endpoints until the evidence from clinical trials is sufficiently strong to support major public health initiatives for prevention.
生物标志物可为癌症预防药物的研发、监测患者对所选干预措施的依从性或进一步明确致癌过程提供有价值的工具。本讨论聚焦于生物效应标志物及其在癌症预防试验中的应用原理。近期有关生物标志物的研究正在探索将其纳入I期、II期和III期化学预防临床试验设计。它们在临床研究中的应用有望增加可评估药物的数量，并提供有关药物、剂量和给药方案生物学有效性的有价值信息。标志物还可提供信息，有助于选择预防研究的高危人群，并指明被抑制的途径和受影响的致癌阶段。这些信息对于强化长期试验及其他辅助研究的理论依据可能至关重要。本文讨论了结直肠癌发生的生物标志物研究，包括一些近期试验的实例，这些试验可能会影响该预防研究领域的未来进展。这一过程中的关键步骤是将标志物作为以癌症发病率为终点的主要前瞻性观察性和干预性研究的一个方面进行验证。在临床试验的证据足够有力以支持重大公共卫生预防举措之前，我们不能完全确信标志物可作为中间终点。
