The metabolism of cancer cells is mostly depending on glycolysis. In such cases, it is known that the intracellular pH (pHi) of cancer cells increases to alkaline (7.2 to 7.7), whereas the pHi of normal cells is maintained at neutral (6.9 to 7.0). In addition, since cancer cells are undergoing intense glycolysis, there is a mechanism in which pyruvate acid becomes excessive in cancer cells and is converted to lactic acid and released from the cells to maintain alkalinity. Due to this mechanism, the tumor microenvironment (TME) is acidic. In recent years, it has been found that various cancer therapies are not very effective when this acidic state exists. In an experimental study using lung cancer cells, it was reported that a 0.4 increase in pHi resulted in a 2000-fold increase in doxorubicin resistance. The favorable effect of alkalization of the acidic TME with cancer therapies has been reported in several clinical studies.
Although interfering pH of TME is a potential treatment option for cancer cells, there are several issues to address. First, in clinical settings, urinary pH increases after providing guidance on dietary improvement and administration of various alkalizing agents, such as bicarbonate or citrate, and may be associated with favorable effects of cancer therapies. However, it remains unclear whether the urinary pH increase reflects the alkalization of TME. Second, the association between pH balance of TME and genetic factors that may influence cancer pH metabolisms also remains unclear. Moreover, we need to investigate the association between the alkalization of TME and the immunologic state of cancer patients. Therefore, our goal is to investigate whether the addition of TME alkalization to conventional treatment will improve the outcomes or not, and how the genetic factors or immunological state influence, or be influenced by pH balance of TME.
With this Research Topic, we aim to improve our understanding of the impact of alkalizing tumor microenvironment on cancer treatment. We welcome both preclinical and clinical research articles; Original Research Articles, Review Articles, Systematic Reviews, Mini-Reviews, and Case Study, addressing the following (but not limited to the following) research topics:
- Molecular biological backgrounds of pH regulation of tumor microenvironment
- Assessment of pH regulation of tumor microenvironment
- Association between pH regulation of tumor microenvironment and genomic factors
- Association between pH regulation of tumor microenvironment and immunological state
- Mechanisms of drug resistance via acidic tumor microenvironment
- Dietary change and pH regulation of tumor microenvironment
- Enhancing cancer treatment response via alkalization of the tumor microenvironment
- The use of alkalizing agents with cancer treatment
Please note: manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) will not be accepted in any of the sections of Frontiers in Oncology.
The metabolism of cancer cells is mostly depending on glycolysis. In such cases, it is known that the intracellular pH (pHi) of cancer cells increases to alkaline (7.2 to 7.7), whereas the pHi of normal cells is maintained at neutral (6.9 to 7.0). In addition, since cancer cells are undergoing intense glycolysis, there is a mechanism in which pyruvate acid becomes excessive in cancer cells and is converted to lactic acid and released from the cells to maintain alkalinity. Due to this mechanism, the tumor microenvironment (TME) is acidic. In recent years, it has been found that various cancer therapies are not very effective when this acidic state exists. In an experimental study using lung cancer cells, it was reported that a 0.4 increase in pHi resulted in a 2000-fold increase in doxorubicin resistance. The favorable effect of alkalization of the acidic TME with cancer therapies has been reported in several clinical studies.
Although interfering pH of TME is a potential treatment option for cancer cells, there are several issues to address. First, in clinical settings, urinary pH increases after providing guidance on dietary improvement and administration of various alkalizing agents, such as bicarbonate or citrate, and may be associated with favorable effects of cancer therapies. However, it remains unclear whether the urinary pH increase reflects the alkalization of TME. Second, the association between pH balance of TME and genetic factors that may influence cancer pH metabolisms also remains unclear. Moreover, we need to investigate the association between the alkalization of TME and the immunologic state of cancer patients. Therefore, our goal is to investigate whether the addition of TME alkalization to conventional treatment will improve the outcomes or not, and how the genetic factors or immunological state influence, or be influenced by pH balance of TME.
With this Research Topic, we aim to improve our understanding of the impact of alkalizing tumor microenvironment on cancer treatment. We welcome both preclinical and clinical research articles; Original Research Articles, Review Articles, Systematic Reviews, Mini-Reviews, and Case Study, addressing the following (but not limited to the following) research topics:
- Molecular biological backgrounds of pH regulation of tumor microenvironment
- Assessment of pH regulation of tumor microenvironment
- Association between pH regulation of tumor microenvironment and genomic factors
- Association between pH regulation of tumor microenvironment and immunological state
- Mechanisms of drug resistance via acidic tumor microenvironment
- Dietary change and pH regulation of tumor microenvironment
- Enhancing cancer treatment response via alkalization of the tumor microenvironment
- The use of alkalizing agents with cancer treatment
Please note: manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) will not be accepted in any of the sections of Frontiers in Oncology.
