Repositioning of proton pump inhibitors in cancer therapy

Repositioning of proton pump inhibitors in cancer therapy — download the full PPI from Cancer Chemother Pharmacol by Zhen-Ning Lui, Bing Tian, and Xiu-Li Guo.

 

Many of you may be aware that I have concentrated my cancer research on the glycolytic nature of many cancers. Cancers that are glycolytic, such as GBM and triple negative breast cancer, primarily rely on glycolysis for the generation of ATP, rather than mitochondrial ox-phos. The end product of glycolysis is pyruvate, which then will be converted into lactic acid. These glycolytic cancer cells must upregulate their mechanism(s) for effluxing lactic acid, or else they will succumb to necrosis or apoptosis, secondary to acidosis.

Any one or combination of 6 mechanisms may be upregulated, but commonly, the proton pump is one of the mechanisms upregulated.

A study was performed in 2012, in which adult females with metastatic breast cancer were randomly assigned to 3 arms: Arm A; Docetaxol 75 mg/m2 and cisplatin 75 mg/m2 on day 4, repeat q 21 days; Arm B; The same chemotherapy plus oral esomeprazole 80 mg bid on days 1-3, Arm C; The same as Arm B except esomeprazole 100 mg bid. Median progression free survival: Arm A (N = 33) 7.5 months; Arm B (N = 30) 10.9 months; Arm C (N= 31) 9.5 months. Among 17 patients with triple negative breast cancer this difference was bigger with median PFS of 9.5 and 3.3 months respectively.

The reason that the great difference was seen in the triple negative group, was that triple negative breast cancer is typically the most glycolytic of the breast cancers. Although the data indicates that long term use of proton pump inhibitors in the healthy population may lead to nutritional deficiencies, as well as altering the bacterial flora, the data suggests using PPIs may be a helpful adjunct in patients with advanced-stage glycolytic cancers.

healthyliving August 27th, 2019

Posted In: cancer care, Cancer Prevention

Tags: cancer, cancer care, glycolysis, glycolytic cancer, metastatic breast cancer, proton pump inhibitors