Słotwiński Robert, Słotwińska Sylwia Małgorzata
Department of Immunology, Biochemistry and Nutrition, Medical University of Warsaw, Warsaw, Poland.
Department of Oral Hygiene, Medical University of Warsaw, Warsaw, Poland.
Cent Eur J Immunol. 2021;46(3):388-394. doi: 10.5114/ceji.2021.109693. Epub 2021 Oct 6.
Despite tremendous progress in the treatment of many cancer types, leading to a significant increase in survival, pancreatic ductal adenocarcinoma (PDAC) is still burdened with high mortality rates (5-year survival rate < 9%) due to late diagnosis, aggressiveness, and a lack of more effective treatment methods. Early diagnosis and new therapeutic approaches based on the adaptive metabolism of the tumor in a nutrient-deficient environment are expected to improve the future treatment of PDAC patients. It was found that blocking selected metabolic pathways related to the local adaptive metabolic activity of pancreatic cancer cells, improving nutrient acquisition and metabolic crosstalk within the microenvironment to sustain proliferation, may inhibit cancer development, increase cancer cell death, and increase sensitivity to other forms of treatment (e.g., chemotherapy). The present review highlights selected metabolic signaling pathways and their regulators aimed at inhibiting the neoplastic process. Particular attention is paid to the adaptive metabolism of pancreatic cancer, including fatty acids, autophagy, macropinocytosis, and deregulated cell-surface glycoproteins, which promotes cancer cell development in an oxygen-deficient and nutrient-poor environment.
尽管在许多癌症类型的治疗方面取得了巨大进展，使生存率显著提高，但胰腺导管腺癌（PDAC）由于诊断较晚、侵袭性强以及缺乏更有效的治疗方法，死亡率仍然很高（5年生存率<9%）。基于肿瘤在营养缺乏环境中的适应性代谢的早期诊断和新治疗方法有望改善未来PDAC患者的治疗。研究发现，阻断与胰腺癌细胞局部适应性代谢活性相关的特定代谢途径，改善微环境内的营养获取和代谢串扰以维持增殖，可能会抑制癌症发展、增加癌细胞死亡，并提高对其他治疗形式（如化疗）的敏感性。本综述重点介绍了旨在抑制肿瘤形成过程的特定代谢信号通路及其调节因子。特别关注胰腺癌的适应性代谢，包括脂肪酸、自噬、巨胞饮作用以及失调的细胞表面糖蛋白，这些在缺氧和营养匮乏的环境中促进癌细胞发展。
