Hephaestus Laboratory, School of Chemistry, Faculty of Science, Democritus University of Thrace, Kavala University Campus, 65404 Kavala, Greece.
Laboratory of Inorganic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, 15771 Athens, Greece.
Front Biosci (Landmark Ed). 2024 Sep 26;29(10):345. doi: 10.31083/j.fbl2910345.
Since 2000s, we have outlined the multifaceted role of inflammation in several aspects of cancer, via specific inflammatory mediators, including the platelet activating factor (PAF) and PAF-receptor (PAFR) related signaling, which affect important inflammatory junctions and cellular interactions that are associated with tumor-related inflammatory manifestations. It is now well established that disease-related unresolved chronic inflammatory responses can promote carcinogenesis. At the same time, tumors themselves are able to promote their progression and metastasis, by triggering an inflammation-related vicious cycle, in which PAF and its signaling play crucial role(s), which usually conclude in tumor growth and angiogenesis. In parallel, new evidence suggests that PAF and its signaling also interact with several inflammation-related cancer treatments by inducing an antitumor immune response or, conversely, promoting tumor recurrence. Within this review article, the current knowledge and future perspectives of the implication of PAF and its signaling in all these important aspects of cancer are thoroughly re-assessed. The potential beneficial role of PAF-inhibitors and natural or synthetic modulators of PAF-metabolism against tumors, tumor progression and metastasis are evaluated. Emphasis is given to natural and synthetic molecules with dual anti-PAF and anti-cancer activities (Bio-DAPAC-tives), with proven evidence of their antitumor potency through clinical trials, as well as on metal-based anti-inflammatory mediators that constitute a new class of potent inhibitors. The way these compounds may promote anti-tumor effects and modulate the inflammatory cellular actions and immune responses is also discussed. Limitations and future perspectives on targeting of PAF, its metabolism and receptor, including PAF-related inflammatory signaling, as part(s) of anti-tumor strategies that involve inflammation and immune response(s) for an improved outcome, are also evaluated.
自 21 世纪初以来，我们通过特定的炎症介质，包括血小板激活因子（PAF）及其受体（PAFR）相关信号通路，概述了炎症在癌症多个方面的多效性作用，这些介质影响与肿瘤相关炎症表现相关的重要炎症连接和细胞相互作用。现在已经明确，与疾病相关的未解决的慢性炎症反应可以促进致癌作用。同时，肿瘤本身也能够通过触发与炎症相关的恶性循环来促进其进展和转移，在这个恶性循环中，PAF 及其信号通路发挥着关键作用，通常导致肿瘤生长和血管生成。与此同时，新的证据表明，PAF 及其信号通路也通过诱导抗肿瘤免疫反应或相反地促进肿瘤复发，与几种与炎症相关的癌症治疗相互作用。在这篇综述文章中，我们彻底重新评估了 PAF 及其信号在癌症所有这些重要方面的作用的当前知识和未来展望。评估了 PAF 抑制剂及其代谢物天然或合成调节剂对肿瘤、肿瘤进展和转移的潜在有益作用。重点关注具有双重抗 PAF 和抗癌活性的天然和合成分子（Bio-DAPAC-tives），这些分子通过临床试验证明了其抗肿瘤效力，以及基于金属的抗炎介质，它们构成了一类新的有效抑制剂。还讨论了这些化合物如何促进抗肿瘤作用，以及调节炎症细胞作用和免疫反应的方式。还评估了靶向 PAF、其代谢物和受体，包括与炎症和免疫反应相关的 PAF 相关炎症信号通路，作为涉及炎症和免疫反应以改善结果的抗肿瘤策略的一部分的局限性和未来展望。
