Related Experiment Video

Updated: May 18, 2026

Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures
07:48

Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures

Published on: December 26, 2016

Targeting the metabolic microenvironment of tumors

Kate M Bailey1, Jonathan W Wojtkowiak, Arig Ibrahim Hashim

  • 1Department of Imaging and Metabolism, H. Lee Moffitt Cancer Center, Tampa, FL, USA.

Advances in Pharmacology (San Diego, Calif.)
|September 11, 2012
PubMed

Insights

Tumor cells exhibit aerobic glycolysis, a phenomenon exacerbated by hypoxia. Targeting these metabolic alterations and their associated pathways shows promise for enhancing cancer therapy and reducing metastasis.

Area of Science:

  • Oncology
  • Cancer Metabolism
  • Tumor Microenvironment

Background:

  • Otto Warburg's 1924 observation of aerobic glycolysis in tumors and PET-CT imaging highlighted altered tumor metabolism.
  • Tumor growth leads to hypoxia, activating pathways like HIF1α, mTOR, and UPR, which are dysregulated in cancer.
  • Tumor hypoxia and acidosis promote metastasis and reduce drug efficacy via mechanisms like ion trapping.

Purpose of the Study:

  • To review preclinical and clinical drugs targeting aerobic glycolysis, acidosis, and hypoxia response pathways in cancer.
  • To summarize therapeutic strategies for manipulating tumor hypoxia and acidosis.

Main Methods:

  • Comprehensive literature review of preclinical and clinical studies.
  • Analysis of drugs targeting aerobic glycolysis, proton transporters, and hypoxia-inducible factors.

Main Results:

  • Dysregulated hypoxia response pathways (HIF1α, mTOR, UPR) in tumors exacerbate hypoxia and acidosis.
  • Tumor acidosis enhances metastatic potential and confers drug resistance.
  • Several drugs targeting these pathways are under clinical and preclinical development.

Conclusions:

  • Targeting tumor aerobic glycolysis, acidosis, and hypoxia offers a promising therapeutic strategy.
  • Manipulating these common tumor phenotypes can provide significant clinical benefit for cancer patients.

Related Concept Videos

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...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
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,...
Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.