Belizario Jose E, Loggulo Angela F
Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Avenida Lineu Prestes, 1524, São Paulo, CEP 05508-900, Brazil.
Department of Pathology, Paulista School of Medicine, Federal University of São Paulo, Rua Sena Madureira, 1500, São Paulo, CEP 04021-001, Brazil.
Cancer Drug Resist. 2019 Sep 19;2(3):527-538. doi: 10.20517/cdr.2018.009. eCollection 2019.
Breast cancer is the most common cancer in the world. Despite advances in early detection and understanding of the molecular bases of breast cancer biology, approximately 30% of all patients with early-stage breast cancer have metastatic disease. Breast cancers are comprised of molecularly distinct subtypes that respond differently to pathway-targeted therapies and neoadjuvant systemic therapy. However, no tumor response is observed in some cases and development of resistance is most commonly seen in patients with heterogeneous breast cancer subtype. To offer better treatment with increased efficacy and low toxicity of selecting therapies, new technologies that incorporate clinical and molecular characteristics of intratumoral heterogeneity have been investigated. This short review provides some examples of integrative omics approaches (genome, epigenome, transcriptome, immune profiling) and mathematical/computational analyses that provide mechanistic and clinically relevant insights into underlying differences in breast cancer subtypes and patients'responses to specific therapies.
乳腺癌是全球最常见的癌症。尽管在早期检测以及对乳腺癌生物学分子基础的认识方面取得了进展，但所有早期乳腺癌患者中仍约有30%发生了转移性疾病。乳腺癌由分子特征不同的亚型组成，这些亚型对通路靶向治疗和新辅助全身治疗的反应不同。然而，在某些情况下未观察到肿瘤反应，并且耐药性的出现最常见于异质性乳腺癌亚型的患者中。为了通过提高所选治疗方法的疗效和降低毒性来提供更好的治疗，人们对纳入肿瘤内异质性临床和分子特征的新技术进行了研究。这篇简短的综述提供了一些整合组学方法（基因组、表观基因组、转录组、免疫谱分析）以及数学/计算分析的实例，这些方法为乳腺癌亚型的潜在差异以及患者对特定治疗的反应提供了机制和临床相关的见解。
