Bhatnagar Kartik, Raju Sharon, Patki Ninad, Motiani Rajender K, Chaudhary Sarika
Department of Biotechnology, School of Engineering and Applied Sciences, Bennett University, Plot Nos. 8-11, Tech Zone 2, Greater Noida, Uttar Pradesh 201310, India.
Laboratory of Calciomics and Systemic Pathophysiology, Regional Centre for Biotechnology (RCB), Faridabad-Gurugram Expressway, Faridabad, Haryana 121001, India.
Semin Cancer Biol. 2025 Jul;112:1-19. doi: 10.1016/j.semcancer.2025.02.011. Epub 2025 Feb 28.
Cancer remains the second leading cause of death worldwide, emphasizing the critical need for effective treatment and control strategies. Essential minerals such as copper, iron, zinc, selenium, phosphorous, calcium, and magnesium are integral to various biological processes and significantly influence cancer progression through altered metabolic pathways. For example, dysregulated copper levels promote tumor growth, while cancer cells exhibit an increased dependency on iron for signaling and redox reactions. Zinc influences tumor development through pathways such as Akt-p21. Selenium, primarily through its role in selenoproteins, exhibits anticancer potential but may also contribute to tumor progression. Similarly, dietary phosphate exacerbates tumorigenesis, metastasis, and angiogenesis through signaling pathway activation. Calcium, the most abundant mineral in the body, is tightly regulated within cells, and its dysregulation is a hallmark of various cancers. Magnesium deficiency, on the other hand, promotes cancer progression by fostering inflammation and free radical-induced DNA mutations. Interestingly, magnesium also plays a dual role, with low levels enhancing epithelial-mesenchymal transition (EMT), a critical process in cancer metastasis. This complex interplay of essential minerals underscores their potential as therapeutic targets. Dysregulation of these minerals and their pathways could be exploited to selectively target cancer cells, offering novel therapeutic strategies. This review summarizes current research on the abnormal accumulation or depletion of these microelements in tumor biology, drawing evidence from animal models, cell lines, and clinical samples. We also highlight the potential of these minerals as biomarkers for cancer diagnosis and prognosis, as well as therapeutic approaches involving metal chelators, pharmacological agents, and nanotechnology. By highlighting the intricate roles of these minerals in cancer biology, we aim to inspire further research in this critical yet underexplored area of oncology.
癌症仍然是全球第二大死因，这凸显了对有效治疗和控制策略的迫切需求。铜、铁、锌、硒、磷、钙和镁等必需矿物质是各种生物过程不可或缺的一部分，并通过改变代谢途径显著影响癌症进展。例如，铜水平失调会促进肿瘤生长，而癌细胞对铁在信号传导和氧化还原反应中的依赖性增加。锌通过Akt-p21等途径影响肿瘤发展。硒主要通过其在硒蛋白中的作用展现出抗癌潜力，但也可能促进肿瘤进展。同样，膳食磷通过信号通路激活加剧肿瘤发生、转移和血管生成。钙是人体中含量最丰富的矿物质，在细胞内受到严格调控，其失调是各种癌症的一个标志。另一方面，镁缺乏通过促进炎症和自由基诱导的DNA突变来促进癌症进展。有趣的是，镁也具有双重作用，低水平会增强上皮-间质转化（EMT），这是癌症转移中的一个关键过程。必需矿物质的这种复杂相互作用突出了它们作为治疗靶点的潜力。这些矿物质及其途径的失调可被利用来选择性地靶向癌细胞，提供新的治疗策略。本综述总结了当前关于这些微量元素在肿瘤生物学中异常积累或消耗的研究，从动物模型、细胞系和临床样本中获取证据。我们还强调了这些矿物质作为癌症诊断和预后生物标志物的潜力，以及涉及金属螯合剂、药物制剂和纳米技术的治疗方法。通过强调这些矿物质在癌症生物学中的复杂作用，我们旨在激发在这个关键但未充分探索的肿瘤学领域的进一步研究。
