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Abstract：
Energy metabolism is a hub of governing all processes at cellular and organismal levels such as, on one hand, reparable vs. irreparable cell damage, cell fate (proliferation, survival, apoptosis, malignant transformation etc.), and, on the other hand, carcinogenesis, tumor development, progression and metastazing versus anti-cancer protection and cure. The orchestrator is the mitochondria who produce, store and invest energy, conduct intracellular and systemically relevant signals decisive for internal and environmental stress adaptation, and coordinate corresponding processes at cellular and organismal levels. Consequently, the quality of mitochondrial health and homeostasis is a reliable target for health risk assessment at the stage of reversible damage to the health followed by cost-effective personalized protection against health-to-disease transition as well as for targeted protection against the disease progression (secondary care of cancer patients against growing primary tumors and metastatic disease). The energy reprogramming of non-small cell lung cancer (NSCLC) attracts particular attention as clinically relevant and instrumental for the paradigm change from reactive medical services to predictive, preventive and personalized medicine (3PM). This article provides a detailed overview towards mechanisms and biological pathways involving metabolic reprogramming (MR) with respect to inhibiting the synthesis of biomolecules and blocking common NSCLC metabolic pathways as anti-NSCLC therapeutic strategies. For instance, mitophagy recycles macromolecules to yield mitochondrial substrates for energy homeostasis and nucleotide synthesis. Histone modification and DNA methylation can predict the onset of diseases, and plasma C7 analysis is an efficient medical service potentially resulting in an optimized healthcare economy in corresponding areas. The MEMP scoring provides the guidance for immunotherapy, prognostic assessment, and anti-cancer drug development. Metabolite sensing mechanisms of nutrients and their derivatives are potential MR-related therapy in NSCLC. Moreover, miR-495-3p reprogramming of sphingolipid rheostat by targeting Sphk1, 22/FOXM1 axis regulation, and A2 receptor antagonist are highly promising therapy strategies. TFEB as a biomarker in predicting immune checkpoint blockade and redox-related lncRNA prognostic signature (redox-LPS) are considered reliable predictive approaches. Finally, exemplified in this article metabolic phenotyping is instrumental for innovative population screening, health risk assessment, predictive multi-level diagnostics, targeted prevention, and treatment algorithms tailored to personalized patient profiles-all are essential pillars in the paradigm change from reactive medical services to 3PM approach in overall management of lung cancers. This article highlights the 3PM relevant innovation focused on energy metabolism as the hub to advance NSCLC management benefiting vulnerable subpopulations, affected patients, and healthcare at large.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s13167-024-00357-5.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s13167-024-00357-5.
摘要：
能量代谢是控制细胞和生物体水平的所有过程的枢纽，例如，一方面,可修复的vs.无法修复的细胞损伤，细胞命运（增殖，生存,凋亡，恶性转化等。),and,另一方面,致癌作用，肿瘤发展，进展和转移与抗癌保护和治愈。编排者是产生线粒体的人，储存和投资能源，传导细胞内和系统相关的信号，对内部和环境应激适应起决定性作用，并在细胞和有机体层面协调相应的过程。因此,线粒体健康和体内平衡的质量是健康风险评估的可靠目标,可在可逆损害健康阶段进行健康风险评估,然后进行具有成本效益的个性化保护,防止健康-疾病转变,并有针对性地防止疾病进展(癌症患者的二级保健,防止增长的原发性肿瘤和转移性疾病).非小细胞肺癌（NSCLC）的能量重编程引起了特别的关注，因为它具有临床相关性，并且有助于从反应性医疗服务到预测性医疗服务的范式转变。预防和个性化医疗（3PM）。本文提供了有关抑制生物分子合成和阻断常见NSCLC代谢途径作为抗NSCLC治疗策略的涉及代谢重编程（MR）的机制和生物途径的详细概述。例如,线粒体自噬回收大分子以产生用于能量稳态和核苷酸合成的线粒体底物。组蛋白修饰和DNA甲基化可以预测疾病的发生，血浆C7分析是一种有效的医疗服务，可能导致相应地区的优化医疗经济。MEMP评分为免疫治疗提供指导，预后评估，和抗癌药物的开发。营养素及其衍生物的代谢物感知机制是NSCLC中潜在的MR相关治疗。此外，miR-495-3p通过靶向Sphk1,22/FOXM1轴调控对鞘脂变阻器的重编程,和A2受体拮抗剂是非常有前途的治疗策略。TFEB作为预测免疫检查点阻断和氧化还原相关lncRNA预后特征（氧化还原-LPS）的生物标志物被认为是可靠的预测方法。最后,本文中举例说明的代谢表型有助于创新的人群筛查，健康风险评估,预测性多级诊断，有针对性的预防,和针对个性化患者资料量身定制的治疗算法-所有这些都是肺癌整体管理中从被动医疗服务到3PM方法的范式转变的重要支柱。本文重点介绍了以能量代谢为中心的3PM相关创新，以促进NSCLC管理，使脆弱的亚群受益。受影响的患者，和整个医疗保健。
■在线版本包含补充材料，可在10.1007/s13167-024-00357-5获得。
■在线版本包含补充材料，可在10.1007/s13167-024-00357-5获得。
