Matossian Margarite D, Giardina Alexandra A, Wright Maryl K, Elliott Steven, Loch Michelle M, Nguyen Khoa, Zea Arnold H, Lau Frank H, Moroz Krzysztof, Riker Adam I, Jones Steven D, Martin Elizabeth C, Bunnell Bruce A, Miele Lucio, Collins-Burow Bridgette M, Burow Matthew E
Section of Hematology and Oncology, Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA.
Biospecimen Core Laboratory, Louisiana Cancer Research Center, New Orleans, Louisiana, USA.
Womens Health Rep (New Rochelle). 2020 Sep 24;1(1):383-392. doi: 10.1089/whr.2020.0037. eCollection 2020.
Despite a decline in overall incidence rates for cancer in the past decade, due in part to impressive advancements in both diagnosis and treatment, breast cancer (BC) remains the leading cause of cancer-related deaths in women. BC alone accounts for ∼30% of all new cancer diagnoses in women worldwide. Triple-negative BC (TNBC), defined as having no expression of the estrogen or progesterone receptors and no amplification of the HER2 receptor, is a subtype of BC that does not benefit from the use of estrogen receptor-targeting or HER2-targeting therapies. Differences in socioeconomic factors and cell intrinsic and extrinsic characteristics have been demonstrated in Black and White TNBC patient tumors. The emergence of patient-derived xenograft (PDX) models as a surrogate, translational, and functional representation of the patient with TNBC has led to the advances in drug discovery and testing of novel targeted approaches and combination therapies. However, current established TNBC PDX models fail to represent the diverse patient population and, most importantly, the specific ethnic patient populations that have higher rates of incidence and mortality. The primary aim of this review is to emphasize the importance of using clinically relevant translatable tumor models that reflect TNBC human tumor biology and heterogeneity in high-risk patient populations. The focus is to highlight the complexity of BC as it specifically relates to the management of TNBC in Black women. We discuss the importance of utilizing PDX models to study the extracellular matrix (ECM), and the distinct differences in ECM composition and biophysical properties in Black and White women. Finally, we demonstrate the crucial importance of PDX models toward novel drug discovery in this patient population.
尽管在过去十年中癌症的总体发病率有所下降，这在一定程度上得益于诊断和治疗方面的显著进展，但乳腺癌（BC）仍然是女性癌症相关死亡的主要原因。仅BC就占全球女性所有新癌症诊断病例的约30%。三阴性乳腺癌（TNBC）被定义为不表达雌激素或孕激素受体且HER2受体无扩增，是一种BC亚型，无法从使用雌激素受体靶向治疗或HER2靶向治疗中获益。在黑人和白人TNBC患者的肿瘤中，已证实社会经济因素以及细胞内在和外在特征存在差异。患者来源的异种移植（PDX）模型作为TNBC患者的替代、转化和功能代表的出现，推动了新型靶向方法和联合疗法的药物发现和测试进展。然而，目前已建立的TNBC PDX模型未能代表多样化的患者群体，最重要的是，未能代表发病率和死亡率较高的特定种族患者群体。本综述的主要目的是强调使用反映TNBC人类肿瘤生物学和高危患者群体异质性的临床相关可转化肿瘤模型的重要性。重点是突出BC的复杂性，特别是与黑人女性TNBC管理相关的复杂性。我们讨论了利用PDX模型研究细胞外基质（ECM）的重要性，以及黑人和白人女性ECM组成和生物物理特性的明显差异。最后，我们证明了PDX模型在该患者群体新型药物发现方面的至关重要性。
