Isaac Powell, Cullen Hudson, Emily Teslow, Elisabeth Heath, Avraham Raz, Aliccia Bollig-Fischer
Wayne State University Medical School, Detroit, USA.
Karmanos Cancer Institute, Detroit, USA.
Cancer Metastasis Rev. 2025 Mar 19;44(2):41. doi: 10.1007/s10555-025-10259-1.
Since 1976, Surveillance Epidemiology End Results (SEER) began collecting ethnicity data for the National Cancer Institute. The incidence of prostate cancer (PCa) among African American men (AAM) has been 60-70% higher than any other ethnicity and mortality rate 2 to 3 times greater than European American men (EAM), and those data have not changed. We reported in 2010 that PCa grows faster among AAM compared to EAM. In 2013, we utilized bioinformatics and ingenuity gene network analysis and in silico analysis to identify driver genes responsible for "racial" disparity. Genes associated with lipid metabolism were more expressed among EAM and genes associated with inflammation were more expressed among AAM. In 2021, we unraveled the network of the Ingenuity gene analysis and reported that the inflammatory genes, specifically proinflammatory cytokines and chemokines initiated multiple pathways. A literature review of these pathways showed that they induce castrate-resistant PCa (CRPC), metastasis, oxidative stress, DNA damage, cancer stem cells, lineage plasticity, and tumor heterogeneity. These genes and processes will be discussed in detail as to how they are initiated by proinflammatory cytokines and chemokines and how they act in a domino effect. Most importantly, how lineage plasticity changes the chemistry of the cancer stem cells of the original PCa so that it is no longer recognized by current therapy, chemotherapy, and immunotherapy. This suggests a paradigm change of current therapy is necessary to significantly reduce mortality of advanced PCa.
自1976年以来，监测、流行病学与最终结果（SEER）项目开始为美国国立癌症研究所收集种族数据。非裔美国男性（AAM）的前列腺癌（PCa）发病率比其他任何种族高60%-70%，死亡率比欧裔美国男性（EAM）高2至3倍，而且这些数据一直没有变化。我们在2010年报告称，与EAM相比，PCa在AAM中生长得更快。2013年，我们利用生物信息学、 Ingenuity基因网络分析和计算机分析来确定导致“种族”差异的驱动基因。与脂质代谢相关的基因在EAM中表达更高，与炎症相关的基因在AAM中表达更高。2021年，我们解析了Ingenuity基因分析网络，并报告说炎症基因，特别是促炎细胞因子和趋化因子启动了多条途径。对这些途径的文献综述表明，它们会诱导去势抵抗性前列腺癌（CRPC）、转移、氧化应激、DNA损伤、癌症干细胞、谱系可塑性和肿瘤异质性。这些基因和过程将详细讨论它们是如何由促炎细胞因子和趋化因子启动的，以及它们如何以多米诺骨牌效应发挥作用。最重要的是，谱系可塑性如何改变原发性PCa癌症干细胞的化学性质，使其不再被当前的治疗、化疗和免疫疗法所识别。这表明有必要对当前的治疗模式进行改变，以显著降低晚期PCa的死亡率。
