Department of Biology, Georgia State University, Atlanta, GA, USA.
Department of Mathematics and Statistics, Georgia State University, Atlanta, GA, USA; Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
Semin Cancer Biol. 2022 Jun;81:220-231. doi: 10.1016/j.semcancer.2021.03.017. Epub 2021 Mar 22.
Although polyploid cells were first described nearly two centuries ago, their ability to proliferate has only recently been demonstrated. It also becomes increasingly evident that a subset of tumor cells, polyploid giant cancer cells (PGCCs), play a critical role in the pathophysiology of breast cancer (BC), among other cancer types. In BC, PGCCs can arise in response to therapy-induced stress. Their progeny possess cancer stem cell (CSC) properties and can repopulate the tumor. By modulating the tumor microenvironment (TME), PGCCs promote BC progression, chemoresistance, metastasis, and relapse and ultimately impact the survival of BC patients. Given their pro- tumorigenic roles, PGCCs have been proposed to possess the ability to predict treatment response and patient prognosis in BC. Traditionally, DNA cytometry has been used to detect PGCCs.. The field will further derive benefit from the development of approaches to accurately detect PGCCs and their progeny using robust PGCC biomarkers. In this review, we present the current state of knowledge about the clinical relevance of PGCCs in BC. We also propose to use an artificial intelligence-assisted image analysis pipeline to identify PGCC and map their interactions with other TME components, thereby facilitating the clinical implementation of PGCCs as biomarkers to predict treatment response and survival outcomes in BC patients. Finally, we summarize efforts to therapeutically target PGCCs to prevent chemoresistance and improve clinical outcomes in patients with BC.
尽管多倍体细胞在近两个世纪前就被首次描述，但它们的增殖能力直到最近才被证实。越来越明显的是，肿瘤细胞的一个亚群，多倍体巨大癌细胞（PGCC），在乳腺癌（BC）和其他癌症类型的病理生理学中起着关键作用。在 BC 中，PGCC 可以作为治疗诱导应激的反应而出现。它们的后代具有癌症干细胞（CSC）特性，可以重新填充肿瘤。通过调节肿瘤微环境（TME），PGCC 促进 BC 的进展、化疗耐药性、转移和复发，并最终影响 BC 患者的生存。鉴于它们的促肿瘤作用，PGCC 被提出具有预测 BC 治疗反应和患者预后的能力。传统上，DNA 细胞术已被用于检测 PGCCs。该领域将进一步受益于开发使用强大的 PGCC 生物标志物准确检测 PGCC 及其后代的方法。在这篇综述中，我们介绍了 PGCC 在 BC 中的临床相关性的现有知识状态。我们还建议使用人工智能辅助的图像分析管道来识别 PGCC 并绘制它们与其他 TME 成分的相互作用，从而促进将 PGCC 作为生物标志物用于预测 BC 患者的治疗反应和生存结果的临床实施。最后，我们总结了靶向 PGCC 以预防化疗耐药性和改善 BC 患者临床结果的治疗努力。
