Department of Biostatistics, Yale University School of Public Health, New Haven, Connecticut 06520-8040, USA.
Environ Mol Mutagen. 2010 Oct-Dec;51(8-9):897-908. doi: 10.1002/em.20606.
Personalized cancer therapy is likely to be one of the next big advances in our search for a cure for cancer. To be able to treat people in an individualized manner, researchers need to know a great deal about their genetic constitution and the DNA repair status of their tumors. Specific knowledge is required regarding the polymorphisms individuals carry and how these polymorphisms influence responses to therapy. Researchers are actively engaged in biomarker discovery and validation for this purpose. In addition, the design of clinical trials must be reassessed to include new information on biomarkers and drug responses. In this review, we focus on personalized breast cancer therapy. The hypothesis we focus upon in this review is that there is connection between the DNA repair profile of individuals, their breast tumor subtypes, and their responses to cancer therapy. We first briefly review cellular DNA repair pathways that are likely to be impacted by breast cancer therapies. Next, we review the phenotypes of breast tumor subtypes with an emphasis on how a DNA repair deficiency might result in tumorigenesis itself and lead to the chemotherapeutic responses that are observed. Specific examples of breast tumor subtypes and their responses to cancer therapy are given, and we discuss possible DNA repair mechanisms that underlie the responses of tumors to various chemotherapeutic agents. Much is known about breast cancer subtypes and the way each of these subtypes responds to chemotherapy. In addition, we discuss novel design of clinical trials that incorporates rapidly emerging information on biomarkers.
个体化癌症治疗可能是我们寻找癌症治愈方法的下一个重大进展之一。为了能够对患者进行个体化治疗，研究人员需要了解其遗传构成和肿瘤的 DNA 修复状态。需要特定的知识来了解个体携带的多态性以及这些多态性如何影响治疗反应。为此，研究人员正在积极进行生物标志物的发现和验证。此外，临床试验的设计必须重新评估，以纳入有关生物标志物和药物反应的新信息。在这篇综述中，我们重点介绍了个体化乳腺癌治疗。我们在这篇综述中关注的假设是，个体的 DNA 修复谱、他们的乳腺癌亚型及其对癌症治疗的反应之间存在联系。我们首先简要回顾了可能受到乳腺癌治疗影响的细胞 DNA 修复途径。接下来，我们回顾了乳腺癌亚型的表型，重点介绍了 DNA 修复缺陷如何导致肿瘤发生本身，并导致观察到的化疗反应。给出了乳腺癌亚型及其对癌症治疗的反应的具体示例，并讨论了潜在的 DNA 修复机制，这些机制是肿瘤对各种化疗药物反应的基础。我们对乳腺癌亚型及其对化疗的反应方式有了很多了解。此外，我们还讨论了将有关生物标志物的快速涌现信息纳入其中的临床试验的新设计。
