Related Experiment Video

Updated: May 28, 2026

Establishment of an Extracellular Acidic pH Culture System
09:41

Establishment of an Extracellular Acidic pH Culture System

Published on: November 19, 2017

Drug resistance and cellular adaptation to tumor acidic pH microenvironment

Jonathan W Wojtkowiak1, Daniel Verduzco, Karla J Schramm

  • 1Department of Radiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, United States.

Molecular Pharmaceutics
|October 11, 2011
PubMed

Insights

Tumor extracellular acidosis creates a drug resistance barrier, impacting chemotherapy efficacy. Strategies targeting this physiological resistance can improve cancer treatment outcomes.

Area of Science:

  • Oncology
  • Cancer Biology
  • Drug Resistance Mechanisms

Background:

  • Therapeutic resistance is a major cause of cancer mortality.
  • Tumor microenvironment, specifically extracellular acidosis, contributes significantly to drug resistance.
  • High glycolytic flux and poor perfusion lead to low extracellular pH (pHe) in tumors.

Purpose of the Study:

  • To review the impact of extracellular acidosis on chemotherapy drug efficacy.
  • To explore physiological changes in tumor cells induced by acidosis that promote resistance.
  • To discuss therapeutic strategies that overcome or exploit tumor acidosis.

Main Methods:

  • Literature review focusing on extracellular acidosis and drug resistance.
  • Analysis of the 'ion trapping' phenomenon and its effect on drug pharmacokinetics.
  • Examination of cellular adaptations to low pHe, including apoptosis, genetic changes, and p-glycoprotein (pGP) activity.

Main Results:

  • Extracellular acidosis creates a physiological drug barrier, hindering weak base chemotherapy.
  • Weakly acidic therapeutics may be more effective in acidic tumor microenvironments.
  • Acidosis induces cellular changes like reduced apoptosis and increased p-glycoprotein expression, enhancing drug resistance.

Conclusions:

  • Extracellular acidosis is a critical factor in cancer therapeutic resistance.
  • Understanding the pH gradient's impact is vital for designing effective cancer therapies.
  • Targeting tumor acidosis presents a promising strategy to overcome drug resistance.

More Related Videos

MAME Models for 4D Live-cell Imaging of Tumor: Microenvironment Interactions that Impact Malignant Progression08:26

MAME Models for 4D Live-cell Imaging of Tumor: Microenvironment Interactions that Impact Malignant Progression

Published on: February 17, 2012

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down08:59

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down

Published on: December 11, 2017

Related Concept Videos

Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
The Tumor Microenvironment02:17

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
The Tumor Microenvironment02:17

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...