Hamel Katie M, Frazier Trivia P, Williams Christopher, Duplessis Tamika, Rowan Brian G, Gimble Jeffrey M, Sanchez Cecilia G
Obatala Sciences, Inc., New Orleans, LA 70148, USA.
Division of Basic Pharmaceutical Sciences, Xavier University of Louisiana, New Orleans, LA 70125, USA.
Int J Mol Sci. 2024 Feb 27;25(5):2728. doi: 10.3390/ijms25052728.
Female breast cancer accounts for 15.2% of all new cancer cases in the United States, with a continuing increase in incidence despite efforts to discover new targeted therapies. With an approximate failure rate of 85% for therapies in the early phases of clinical trials, there is a need for more translatable, new preclinical in vitro models that include cellular heterogeneity, extracellular matrix, and human-derived biomaterials. Specifically, adipose tissue and its resident cell populations have been identified as necessary attributes for current preclinical models. Adipose-derived stromal/stem cells (ASCs) and mature adipocytes are a normal part of the breast tissue composition and not only contribute to normal breast physiology but also play a significant role in breast cancer pathophysiology. Given the recognized pro-tumorigenic role of adipocytes in tumor progression, there remains a need to enhance the complexity of current models and account for the contribution of the components that exist within the adipose stromal environment to breast tumorigenesis. This review article captures the current landscape of preclinical breast cancer models with a focus on breast cancer microphysiological system (MPS) models and their counterpart patient-derived xenograft (PDX) models to capture patient diversity as they relate to adipose tissue.
女性乳腺癌占美国所有新发癌症病例的15.2%,尽管人们努力研发新的靶向治疗方法,但其发病率仍在持续上升。由于临床试验早期阶段的治疗方法失败率约为85%,因此需要更多可转化的新型临床前体外模型,这些模型应包括细胞异质性、细胞外基质和人源生物材料。具体而言,脂肪组织及其驻留细胞群已被确定为当前临床前模型的必要属性。脂肪来源的基质/干细胞(ASC)和成熟脂肪细胞是乳腺组织组成的正常部分,不仅有助于正常的乳腺生理功能,而且在乳腺癌病理生理学中也发挥着重要作用。鉴于脂肪细胞在肿瘤进展中公认的促肿瘤作用,仍有必要提高当前模型的复杂性,并考虑脂肪基质环境中存在的成分对乳腺肿瘤发生的贡献。这篇综述文章介绍了临床前乳腺癌模型的现状,重点关注乳腺癌微生理系统(MPS)模型及其对应的患者来源异种移植(PDX)模型,以体现与脂肪组织相关的患者多样性。