Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kuwait University, PO Box 24923, Safat 13110, Kuwait.
Expert Rev Anticancer Ther. 2013 Oct;13(10):1229-42. doi: 10.1586/14737140.2013.843455. Epub 2013 Oct 7.
Rapid malignant proliferation, prior to effective tumor neoangiogenesis, creates a microenvironment around solid cancers, which is predominantly hypoxic and characterized by a high interstitial fluid pressure. Presumably as an adaptive response, tumor cells favor metabolic activity with apparently inefficient energy output, and production of intermediates that promote cellular replication, preferentially through anaerobic glycolysis, a phenomenon that persists even in re-established normoxic conditions (anomalously referred to as 'aerobic glycolysis'). Extrusion of the consequently excessive accumulation of lactate and protons decreases extracellular pH, leading to a microenvironment considered conducive to promotion of tumor motility, invasion and metastasis, and one that will invariably influence response to drug treatment. This review will critically assess the evidence forming the basis of current understanding of the precise pH conditions in the extracellular tumor matrix, its regulation by cancer cells and relationship with hypoxia, its relevance to malignant progression and its exploitation for therapeutic advantage.
快速恶性增殖，在有效的肿瘤新生血管形成之前，在实体瘤周围创造了一个微环境，该微环境主要呈缺氧状态，并具有高细胞间液压力的特点。推测作为一种适应性反应，肿瘤细胞偏向于代谢活性，其能量输出明显效率低下，并产生促进细胞复制的中间产物，主要通过无氧糖酵解，即使在重新建立的正常氧条件下（异常地称为“有氧糖酵解”）也是如此。乳酸和质子的过度积累导致细胞外 pH 值降低，从而形成有利于促进肿瘤运动性、侵袭和转移的微环境，这将不可避免地影响对药物治疗的反应。本综述将批判性地评估形成目前对细胞外肿瘤基质中精确 pH 值条件的理解基础的证据，评估癌细胞对其的调节作用及其与缺氧的关系，评估其与恶性进展的相关性及其在治疗优势方面的应用。
