Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Biomedical Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD, USA.
Adv Exp Med Biol. 2021;1311:249-263. doi: 10.1007/978-3-030-65768-0_18.
According to data from the World Health Organization, cardiovascular diseases and cancer are the two leading causes of mortality in the world [1]. Despite the immense effort to study these diseases and the constant innovation in treatment modalities, the number of deaths associated with cardiovascular diseases and cancer is predicted to increase in the coming decades [1]. From 2008 to 2030, due to population growth and population aging in many parts of the world, the number of deaths caused by cancer globally is projected to increase by 45%, corresponding to an annual increase of around four million people [1]. For cardiovascular diseases, this number is six million people [1]. In the United States, treatments for these two diseases are among the most costly and result in a disproportionate impact on low- and middleincome people. As the fight against these fatal diseases continues, it is crucial that we continue our investigation and broaden our understanding of cancer and cardiovascular diseases to innovate our prognostic and treatment approaches. Even though cardiovascular diseases and cancer are usually studied independently [2-12], there are some striking overlaps between their metabolic behaviors and therapeutic targets, suggesting the potential application of cardiovascular disease treatments for cancer therapy. More specifically, both cancer and many cardiovascular diseases have an upregulated glutaminolysis pathway, resulting in low glutamine and high glutamate circulating levels. Similar treatment modalities, such as glutaminase (GLS) inhibition and glutamine supplementation, have been identified to target glutamine metabolism in both cancer and some cardiovascular diseases. Studies have also found similarities in lipid metabolism, specifically fatty acid oxidation (FAO) and synthesis. Pharmacological inhibition of FAO and fatty acid synthesis have proven effective against many cancer types as well as specific cardiovascular conditions. Many of these treatments have been tested in clinical trials, and some have been medically prescribed to patients to treat certain diseases, such as angina pectoris [13, 14]. Other metabolic pathways, such as tryptophan catabolism and pyruvate metabolism, were also dysregulated in both diseases, making them promising treatment targets. Understanding the overlapping traits exhibited by both cancer metabolism and cardiovascular disease metabolism can give us a more holistic view of how important metabolic dysregulation is in the progression of diseases. Using established links between these illnesses, researchers can take advantage of the discoveries from one field and potentially apply them to the other. In this chapter, we highlight some promising therapeutic discoveries that can support our fight against cancer, based on common metabolic traits displayed in both cancer and cardiovascular diseases.
根据世界卫生组织的数据，心血管疾病和癌症是全球两大主要死亡原因[1]。尽管人们为研究这些疾病付出了巨大努力，治疗方式也不断创新，但预计在未来几十年中，与心血管疾病和癌症相关的死亡人数将会增加[1]。从 2008 年到 2030 年，由于世界许多地区的人口增长和人口老龄化，预计全球癌症死亡人数将增加 45%，相当于每年增加约 400 万人[1]。对于心血管疾病，这一数字为 600 万人[1]。在美国，这两种疾病的治疗费用都非常昂贵，而且对中低收入人群的影响不成比例。随着对这些致命疾病的持续抗争，我们必须继续深入研究并拓宽对癌症和心血管疾病的认识，以创新我们的预后和治疗方法。尽管心血管疾病和癌症通常是分开研究的[2-12]，但它们的代谢行为和治疗靶点之间存在一些显著的重叠，这表明心血管疾病的治疗方法可能适用于癌症治疗。更具体地说，癌症和许多心血管疾病都存在上调的谷氨酰胺分解代谢途径，导致循环中谷氨酰胺水平降低，谷氨酸水平升高。已发现类似的治疗方式，如谷氨酰胺酶（GLS）抑制和谷氨酰胺补充，可靶向癌症和一些心血管疾病中的谷氨酰胺代谢。研究还发现脂质代谢存在相似之处，特别是脂肪酸氧化（FAO）和合成。药理学抑制 FAO 和脂肪酸合成已被证明对许多癌症类型以及特定的心血管疾病有效。许多这些治疗方法已经在临床试验中进行了测试，并且一些已经被医学上开给患者用于治疗某些疾病，如心绞痛[13,14]。其他代谢途径，如色氨酸分解代谢和丙酮酸代谢，在这两种疾病中也失调，使其成为有前途的治疗靶点。了解癌症代谢和心血管疾病代谢之间的重叠特征，可以让我们更全面地了解代谢失调在疾病进展中的重要性。利用这些疾病之间的既定联系，研究人员可以利用一个领域的发现，并有可能将其应用于另一个领域。在本章中，我们将基于癌症和心血管疾病中显示的共同代谢特征，强调一些有希望的治疗发现，这些发现可以支持我们对抗癌症的斗争。
