The complex relationship between multiple drug resistance and the tumor pH gradient:a review

作     者：Tomas Koltai 

作者机构：Former Medical Director of the Hospital del Centro Gallego de Buenos AiresBuenos Aires 1006Argentina. 

出 版 物：《Cancer Drug Resistance》 (癌症耐药（英文）)

年 卷 期：2022年第5卷第2期

页      面：277-303页

学科分类：1007[医学-药学(可授医学、理学学位)] 1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

主　　题：Multidrug resistance pH gradient inversion reversion of the pH gradient P-gp pH centered treatment 

摘      要：Multiple drug resistance(MDR)is the tumor’s way of escaping the cytotoxic effects of various unrelated chemotherapeutic *** can be either innate or *** represents the end of the therapeutic pathway,and it practically leaves no treatment *** MDR is an unfulfilled goal,despite the important recent advances in cancer ***,the main cause of death in cancer patients,is a multi-factorial development,and most of its known causes have been thoroughly discussed in the ***,there is one aspect that has not received adequate consideration-intracellular alkalosis-which is part of wider pH deregulation where the pH gradient is inverted,meaning that extracellular pH is decreased and intracellular pH *** situation interacts with MDR and with the proteins involved,such as P-gp,breast cancer resistance protein,and multidrug associated resistance protein ***,there are also situations in which these proteins play no role at all,and where pH takes the *** is the case in ion *** the pH gradient to normal can be an important contribution to managing *** drugs to manipulate pH exist,and most of them are FDA approved and in clinical use for other ***,they have low or no toxicity and are inexpensive compared with any chemotherapeutic *** these drugs and combining them in a reasonable fashion is one of the points proposed in this paper,which discusses the relationship between cancer’s peculiar pH and MDR.