National University Health System, Department of Haematology-Oncology, 5 Lower Kent Ridge Road, Singapore 119074, Singapore.
Expert Opin Drug Metab Toxicol. 2010 Mar;6(3):283-306. doi: 10.1517/17425250903510611.
There has been much interest in generating gene signatures to predict treatment response in breast cancer.
There are at least 15 published studies that describe baseline tumor gene signatures predicting chemotherapy sensitivity. As an extension of these baseline studies, there have been at least 8 published studies evaluating chemotherapy-induced tumor genomic changes over time in human breast cancers.
Studies on chemotherapy-induced gene expression changes were reviewed in detail. Drug-induced biological changes within the tumor shed light on mechanisms of drug resistance and provided valuable insights regarding genes and pathways that were regulated by different drugs, including therapeutic targets that could be exploited to overcome resistance. One study also suggested post-chemotherapy gene signatures to be more predictive of response and survival than the unchallenged baseline signatures.
Studies on chemotherapy-induced changes, although informative, are logistically demanding to execute, often with significant attrition of collected samples resulting in small datasets. They are further limited by heterogeneity of study population, chemotherapy regimens used, timing of the post-therapy sample and definition of response endpoint, making cross-comparisons of studies and data interpretation difficult. Future studies should address these limitations, and should involve larger sample sets and prospective studies for validation.
人们对生成基因特征以预测乳腺癌治疗反应产生了浓厚的兴趣。
至少有 15 项已发表的研究描述了预测化疗敏感性的基线肿瘤基因特征。作为这些基线研究的延伸，至少有 8 项已发表的研究评估了人类乳腺癌中随时间推移的化疗诱导肿瘤基因组变化。
详细回顾了化疗诱导的基因表达变化研究。肿瘤内药物诱导的生物学变化揭示了耐药机制，并为不同药物调节的基因和途径提供了有价值的见解，包括可用于克服耐药性的治疗靶点。一项研究还表明，化疗后基因特征比未经挑战的基线特征更能预测反应和生存。
尽管化疗诱导变化的研究具有启发性，但在执行方面具有挑战性，通常会导致收集的样本大量减少，从而导致数据集较小。它们还受到研究人群异质性、使用的化疗方案、治疗后样本的时间以及反应终点定义的限制，使得研究之间的比较和数据解释变得困难。未来的研究应该解决这些限制，并应涉及更大的样本集和前瞻性研究进行验证。
