Viklund Jenny, Avnet Sofia, De Milito Angelo
Sprint Bioscience, Stockholm. Sweden.
Orthopaedic Pathophysiology and Regenerative Medicine Unit, Istituto Ortopedico Rizzoli, Bologna. Italy.
Curr Med Chem. 2017;24(26):2827-2845. doi: 10.2174/0929867323666161228142849.
Drug resistance and therapeutic failure are important causes of disease relapse and progression and may be considered as major obstacles preventing cure of cancer patients. Tumors use a large number of molecular, biochemical and cellular mechanisms to evade chemotherapy and targeted therapy. Important determinants of drug efficacy are the intrinsic pharmacological characteristics of drugs which may be largely affected by the tumor physiology. One feature of solid tumors is the acidic extracellular pH, resulting from metabolic shift and increased metabolic rates combined with low tissue perfusion due to defective vasculature. Besides its role in tumor pathobiology promoting tumor growth and metastasis, the acidic tumor environment creates a chemical barrier for many anticancer drugs, thus limiting their activity. The content of this review will be focused on the pathobiology of tumor acidosis and on its role in therapeutic resistance.
耐药性和治疗失败是疾病复发和进展的重要原因，可被视为阻碍癌症患者治愈的主要障碍。肿瘤利用大量分子、生化和细胞机制来逃避化疗和靶向治疗。药物疗效的重要决定因素是药物的内在药理学特性，而这可能在很大程度上受到肿瘤生理学的影响。实体瘤的一个特征是细胞外pH呈酸性，这是由于代谢转变、代谢率增加以及由于血管系统缺陷导致的低组织灌注共同作用的结果。除了在促进肿瘤生长和转移的肿瘤病理生物学中发挥作用外，酸性肿瘤环境还为许多抗癌药物形成了化学屏障，从而限制了它们的活性。本综述的内容将聚焦于肿瘤酸中毒的病理生物学及其在治疗耐药性中的作用。
