Targeting Therapy Resistance: When Glutamine Catabolism Becomes Essential
Michael J Lukey1, William P Katt1, Richard A Cerione2
1Department of Molecular Medicine, Cornell University, Ithaca, NY 14853, USA.
Cancer Cell
|May 16, 2018
Summary
Cancer cells adapt to nutrient changes by increasing glutamine breakdown after glycolysis is blocked. This makes lung tumors vulnerable to drugs targeting glutaminase.
Area of Science:
- Oncology
- Cancer Metabolism
- Molecular Biology
Background:
- Targeted metabolic therapies are crucial for cancer treatment.
- Understanding nutrient dependencies in cancer is key.
Purpose of the Study:
- To investigate adaptive metabolic changes in lung squamous cell carcinoma following mTOR inhibition.
- To identify vulnerabilities for targeted therapy.
Main Methods:
- Utilized a mouse model of lung squamous cell carcinoma.
- Analyzed metabolic pathways including glycolysis and glutaminolysis.
- Assessed tumor response to mTOR and glutaminase inhibitors.
Main Results:
- mTOR inhibition suppressed glycolysis but induced adaptive glutamine catabolism.
- Lung squamous cell carcinoma cells showed increased reliance on glutamine.
- Combined inhibition of mTOR and glutaminase demonstrated therapeutic potential.
Conclusions:
- Adaptive glutamine metabolism is a resistance mechanism to mTOR inhibition in lung cancer.
- Targeting glutaminase in combination with mTOR inhibitors may overcome treatment resistance.
Related Concept Videos
02:57Targeted Cancer Therapies
9.0K
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...
There are several types of targeted therapies against...
9.0K
01:25Lipid Catabolism
1.1K
Triglycerides serve as crucial long-term energy storage molecules in microorganisms, providing a dense source of metabolic energy. Their breakdown is mediated by lipases, which hydrolyze triglycerides into glycerol and free fatty acids. Each of these components follows distinct metabolic pathways, ultimately contributing to ATP synthesis and cellular energy homeostasis.Glycerol MetabolismGlycerol, released from triglyceride hydrolysis, is phosphorylated by glycerol kinase to form...
1.1K
01:30Carbohydrate Catabolism
1.2K
Carbohydrate catabolism is a fundamental process in cellular metabolism that enables energy extraction from glucose through two primary pathways: cellular respiration and fermentation. Both pathways begin with glycolysis, which operates independently of oxygen availability.Glycolysis: A Shared Starting PointGlycolysis is an oxygen-independent process that breaks down glucose into two molecules of pyruvic acid. During this process, a net gain of two ATP molecules and two NADH molecules is...
1.2K
01:18Amino Acid Catabolism
1.2K
Microorganisms rely on proteins as an essential carbon and energy source, particularly in environments with limited polysaccharides or lipids. However, proteins are too large to cross the plasma membrane unaided, necessitating enzymatic degradation. Microbes secrete extracellular proteases and peptidases that hydrolyze proteins into peptides, which can then be transported across the membrane. Once inside the cell, intracellular proteases degrade these peptides into free amino acids, which...
1.2K
01:25Compounds Essential to Human Function
10.5K
The human body is composed of cells that are fundamentally made up of several different molecules. These molecules are essential to carry out all physiological processes in the body and are broadly classified into organic and inorganic based on their chemical structures.
Inorganic Compounds Essential to Human Functioning
Inorganic compounds essential to human functioning include water, salts, acids, and bases. These compounds are inorganic, i.e., they do not have a carbon-hydrogen bond. Water...
Inorganic Compounds Essential to Human Functioning
Inorganic compounds essential to human functioning include water, salts, acids, and bases. These compounds are inorganic, i.e., they do not have a carbon-hydrogen bond. Water...
10.5K
01:19Types of Chemical Reactions: Anabolic and Catabolic
20.8K
The first law of thermodynamics holds that energy can neither be created nor destroyed—it can only change form. An organism's essential function is to consume (ingest) energy and molecules in the foods we eat, convert some of it into fuel for movement, sustain our body functions, and build and maintain our body structures. There are two types of reactions that accomplish this: anabolism and catabolism.
Anabolism is the process of combining smaller, simpler molecules into larger, more...
Anabolism is the process of combining smaller, simpler molecules into larger, more...
20.8K