Tumor pH controls the <i>in vivo</i> efficacy of weak acid and base chemotherapeutics

Gerweck, Leo E.; Vijayappa, Shashirekha; Kozin, Sergey V.

doi:10.1158/1535-7163.mct-06-0024

Cited by 320 publications

(247 citation statements)

References 26 publications

Supporting

Mentioning

233

Contrasting

Unclassified

Order By: Relevance

“…Cellular drug uptake and intracellular targeting are key factors for a successful anticancer treatment and both mechanisms are influenced by pH e . Extracellular acidity reduces the intracellular concentration of chemotherapeutic agents, mainly weak base drugs, through a mechanism termed "ion trapping", and based on ion protonation of drugs [99][100][101][102]. Thus, the reversion of this pH gradient may strongly facilitate the successful treatment.…”

Section: Acidity Promotes Resistance To Drug and Radio-treatmentmentioning

confidence: 99%

“…Thus, the reversion of this pH gradient may strongly facilitate the successful treatment. Indeed, several in vitro and in vivo studies show that low pH reduces uptake and efficacy of weak base chemotherapeutics, such as anthracyclines (e.g., doxorubicin), anthraquinones (e.g., mitoxantrone), and vinca alkaloids (e.g., vincristine and vinblastine) [101,103]. On the contrary, alkalization of extracellular environment enhances intracellular accumulation and cytotoxicity of some of these weak base drugs [104].…”

Section: Acidity Promotes Resistance To Drug and Radio-treatmentmentioning

confidence: 99%

See 1 more Smart Citation

The acidic microenvironment as a possible niche of dormant tumor cells

Peppicelli

Andreucci

Ruzzolini

et al. 2017

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

Section: Acidity Promotes Resistance To Drug and Radio-treatmentmentioning

confidence: 99%

Section: Acidity Promotes Resistance To Drug and Radio-treatmentmentioning

confidence: 99%

The acidic microenvironment as a possible niche of dormant tumor cells

Peppicelli

Andreucci

Ruzzolini

et al. 2017

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

“…Alternative strategies that target the particularities of the tumour phenotype may provide tumour-specific agents that hold the advantage of sparing normal tissue [59][60][61], which is not the case with classical chemotherapy. Such strategies may prove beneficial alone or in combination with presently employed cytotoxic agents [62].…”

Section: Harnessing Phenotype In Combating Tumour Growthmentioning

confidence: 99%

Hypoxia and cancer

2007

View full text Add to dashboard Cite

A major feature of solid tumours is hypoxia, decreased availability of oxygen, which increases patient treatment resistance and favours tumour progression. How hypoxic conditions are generated in tumour tissues and how cells respond to hypoxia are essential questions in understanding tumour progression and metastasis. Massive tumour-cell proliferation distances cells from the vasculature, leading to a deficiency in the local environment of blood carrying oxygen and nutrients. Such hypoxic conditions induce a molecular response, in both normal and neoplastic cells, that drives the activation of a key transcription factor; the hypoxia-inducible factor. This transcription factor regulates a large panel of genes that are exploited by tumour cells for survival, resistance to treatment and escape from a nutrient-deprived environment. Although now recognized as a major contributor to cancer progression and to treatment failure, the precise role of hypoxia signalling in cancer and in prognosis still needs to be further defined. It is hoped that a better understanding of the mechanisms implicated will lead to alternative and more efficient therapeutic approaches.

show abstract

“…Finally, the acidic tumour pH e , while contributing to cancer development, provides a therapeutic opportunity: the design of drugs that take advantage of this to modulate bioavailability [137][138][139]. A related approach is based on the targeting of hypoxia.…”

Section: Exploiting the Ph/tumour Microenvironment/ Metabolism Inter-mentioning

confidence: 99%

Interactions of ion transporters and channels with cancer cell metabolism and the tumour microenvironment

Andersen

Moreira

Pedersen

2014

Phil. Trans. R. Soc. B

View full text Add to dashboard Cite

Major changes in intra-and extracellular pH homoeostasis are shared features of most solid tumours. These changes stem in large part from the metabolic shift of most cancer cells towards glycolytic metabolism and other processes associated with net acid production. In combination with oncogenic signalling and impact from factors in the tumour microenvironment, this upregulates acid-extruding plasma membrane transport proteins which maintain intracellular pH normal or even more alkaline compared with that of normal cells, while in turn acidifying the external microenvironment. Mounting evidence strongly indicates that this contributes significantly to cancer development by favouring e.g. cancer cell migration, invasion and chemotherapy resistance. Finally, while still under-explored, it seems likely that non-cancer cells in the tumour microenvironment also exhibit altered pH regulation and that this may contribute to their malignant properties. Thus, the physical tumour microenvironment and the cancer and stromal cells within it undergo important reciprocal interactions which modulate the tumour pH profile, in turn severely impacting on the course of cancer progression. Here, we summarize recent knowledge of tumour metabolism and the tumour microenvironment, placing it in the context of tumour pH regulation, and discuss how interfering with these properties may be exploited clinically.

show abstract

Tumor pH controls the in vivo efficacy of weak acid and base chemotherapeutics

Abstract: The extracellular pH of tumor

Cited by 320 publications

References 26 publications

The acidic microenvironment as a possible niche of dormant tumor cells

The acidic microenvironment as a possible niche of dormant tumor cells

Hypoxia and cancer

Interactions of ion transporters and channels with cancer cell metabolism and the tumour microenvironment

Contact Info

Product

Resources

About