Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp, Antwerp, Belgium; CellCarta N V, Wilrijk, Belgium.
Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp, Antwerp, Belgium.
Int Rev Cell Mol Biol. 2024;384:77-112. doi: 10.1016/bs.ircmb.2023.10.006. Epub 2024 Feb 10.
Inflammatory breast cancer is an aggressive subtype of breast cancer with dismal patient prognosis and a unique clinical presentation. In the past two decades, molecular profiling technologies have been used in order to gain insight into the molecular biology of IBC and to search for possible targets for treatment. Although a gene signature that accurately discriminates between IBC and nIBC patient samples and preclinical models was identified, the overall genomic and transcriptomic differences are small and ambiguous, mainly due to the limited sample sizes of the evaluated patient series and the failure to correct for confounding effects of the molecular subtypes. Nevertheless, data collected over the past 20 years by independent research groups increasingly support the existence of several IBC-specific biological characteristics. In this review, these features are classified as established, emerging and conceptual hallmarks based on the level of evidence reported in the literature. In addition, a synoptic model is proposed that integrates all hallmarks and that can explain how cancer cell intrinsic mechanisms (i.e. NF-κB activation, genomic instability, MYC-addiction, TGF-β resistance, adaptive stress response, chromatin remodeling, epithelial-to-mesenchymal transition) can contribute to the establishment of the dynamic immune microenvironment associated with IBC. It stands to reason that future research projects are needed to further refine (parts of) this model and to investigate its clinical translatability.
炎性乳腺癌是一种侵袭性乳腺癌亚型，患者预后较差，具有独特的临床表现。在过去的二十年中，人们已经使用分子分析技术来深入了解 IBC 的分子生物学，并寻找可能的治疗靶点。虽然已经确定了一个能够准确区分 IBC 和非炎性乳腺癌患者样本和临床前模型的基因特征，但总体基因组和转录组差异较小且不明确，这主要是由于评估患者系列的样本量有限，以及未能纠正分子亚型的混杂效应。然而，过去 20 年来，独立研究小组收集的数据越来越多地支持几种 IBC 特异性生物学特征的存在。在这篇综述中，这些特征根据文献中报道的证据水平被分类为已确立、新兴和概念性特征。此外，还提出了一个综合所有特征的综合模型，该模型可以解释癌症细胞内在机制（即 NF-κB 激活、基因组不稳定性、MYC 成瘾、TGF-β 抵抗、适应性应激反应、染色质重塑、上皮-间充质转化）如何有助于建立与 IBC 相关的动态免疫微环境。有理由认为，未来需要开展更多的研究项目来进一步完善（部分）该模型，并研究其临床转化性。
