Related Experiment Video

Updated: Nov 8, 2025

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
08:19

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo

Published on: July 20, 2019

6.1K

In cancer, all roads lead to NADPH

Gulam Mohmad Rather1, Alvinsyah Adhityo Pramono2, Zoltan Szekely3

  • 1Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.

Pharmacology & Therapeutics
|April 24, 2021
PubMed

Insights

Cancer cells need more NADPH for growth and survival. Targeting its production offers a new strategy for cancer therapy by disrupting this essential metabolic pathway.

Area of Science:

  • Biochemistry
  • Cancer Biology
  • Metabolic Pathways

Background:

  • Cancer cells exhibit elevated requirements for nicotinamide adenine dinucleotide phosphate (NADPH).
  • NADPH is crucial for nucleotide synthesis and cellular defense against reactive oxygen species (ROS).
  • Several mechanisms contribute to increased NADPH generation in cancer cells.

Purpose of the Study:

  • To elucidate the diverse pathways responsible for elevated NADPH levels in cancer.
  • To identify potential therapeutic targets within NADPH synthesis pathways for cancer treatment.

Main Methods:

  • Review of recent studies on NADPH generation mechanisms in cancer.
  • Analysis of the roles of specific enzymes and signaling pathways (e.g., AKT, NADK, G6PD, malic enzymes, calmodulin).
  • Investigation of NADPH's role in IDH1/2 mutant cancers and oncometabolite production.

Main Results:

  • Activated AKT phosphorylates NAD kinase (NADK), enhancing its activity.
  • Glucose-6-phosphate dehydrogenase and malic enzymes convert NADP to NADPH, often overexpressed in mutant p53 tumors.
  • Calmodulin overexpression also boosts NADK activity.
  • In IDH1/2 mutant cancers, NADPH is essential for generating the oncometabolite D-2-hydroxyglutarate.

Conclusions:

  • The heightened demand for NADPH in cancer cells presents a vulnerability.
  • Targeting the synthesis of NADPH is a promising therapeutic strategy for various cancers.
Keywords:
CalmodulinNADNAD kinaseNADPHROS

More Related Videos

Production and Detection of Reactive Oxygen Species ROS in Cancers07:17

Production and Detection of Reactive Oxygen Species ROS in Cancers

Published on: November 21, 2011

70.5K
Bioorthogonal Chemical Imaging of Cell Metabolism Regulated by Aromatic Amino Acids10:42

Bioorthogonal Chemical Imaging of Cell Metabolism Regulated by Aromatic Amino Acids

Published on: May 12, 2023

1.3K

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,...
6.1K
Role of Reduced Coenzymes NADH and FADH₂01:29

Role of Reduced Coenzymes NADH and FADH₂

The energy released from the breakdown of the chemical bonds within nutrients can be stored either through the reduction of electron carriers or in the bonds of adenosine triphosphate (ATP). In living systems, a small class of compounds functions as mobile electron carriers, molecules that bind to and shuttle high-energy electrons between compounds in pathways. The principal electron carriers that will be considered originate from the B vitamin group and are derivatives of nucleotides; they are...
15.0K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.2K
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
16.5K
Positive Regulator Molecules02:39

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
6.0K
Positive Regulator Molecules01:45

Positive Regulator Molecules

To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
117.0K