Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Treatment Resistant Cancers02:56

Treatment Resistant Cancers

3.3K
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...
3.3K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

7.7K
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...
7.7K
Drugs that Destabilize Microtubules01:10

Drugs that Destabilize Microtubules

2.0K
Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
2.0K
Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

2.1K
Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.1K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

7.5K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
7.5K
Cancer Prevention02:59

Cancer Prevention

6.2K
Several factors can increase the risk of cancer in an individual. About 50% of cancer cases can be prevented by adopting a healthy lifestyle, regular exercise, eating healthy, and following a modest cancer prevention diet. Epidemiological studies have consistently shown that populations with vegetable and fruit-rich diets have reduced the incidence of cancer. On the other hand, populations who have a diet rich in animal fat, red meat, junk food, or high calories are predisposed to cancer.
Some...
6.2K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Anti-Tumor Effects of a Penetratin Peptide Targeting Transcription of E2F-1, 2 and 3a Is Enhanced When Used in Combination with Pemetrexed or Cisplatin.

Cancers·2021
Same author

NAD- and NADPH-Contributing Enzymes as Therapeutic Targets in Cancer: An Overview.

Biomolecules·2020
Same author

Rapid Assessment of Surface Markers on Cancer Cells Using Immuno-Magnetic Separation and Multi-frequency Impedance Cytometry for Targeted Therapy.

Scientific reports·2020
Same author

Toward point-of-care assessment of patient response: a portable tool for rapidly assessing cancer drug efficacy using multifrequency impedance cytometry and supervised machine learning.

Microsystems & nanoengineering·2019

Related Experiment Video

Updated: Jul 18, 2025

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer
06:21

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer

Published on: May 10, 2024

760

Folate trapping is lethal to cancer cells.

Gulam Mohmad Rather1

  • 1Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA.

Chemical Biology & Drug Design
|August 24, 2023
PubMed
Summary

A novel cancer therapy exploits "folate trapping" by inhibiting mitochondrial MTHFD2 (methylene tetrahydrofolate dehydrogenase 2), leading to cancer cell death. This approach targets MTHFD2-overexpressing cancers like breast and colorectal.

Keywords:
MTHFD2folate trappingformatemetabolomics

More Related Videos

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
06:00

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics

Published on: May 14, 2016

11.1K
Dual CRISPR-Interference Strategy for Targeting Synthetic Lethal Interactions Between Non-Coding RNAs in Cancer Cells
07:23

Dual CRISPR-Interference Strategy for Targeting Synthetic Lethal Interactions Between Non-Coding RNAs in Cancer Cells

Published on: May 30, 2025

450

Related Experiment Videos

Last Updated: Jul 18, 2025

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer
06:21

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer

Published on: May 10, 2024

760
Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
06:00

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics

Published on: May 14, 2016

11.1K
Dual CRISPR-Interference Strategy for Targeting Synthetic Lethal Interactions Between Non-Coding RNAs in Cancer Cells
07:23

Dual CRISPR-Interference Strategy for Targeting Synthetic Lethal Interactions Between Non-Coding RNAs in Cancer Cells

Published on: May 30, 2025

450

Area of Science:

  • Biochemistry
  • Metabolic pathways in cancer
  • Enzyme inhibition

Background:

  • Mitochondrial MTHFD2 (methylene tetrahydrofolate dehydrogenase 2) role in cancer cell formate metabolism is unclear.
  • Previous studies explored inhibitors of cytosolic and nuclear MTHFD1/MTHFD2, with limited success.
  • Mitochondrial MTHFD2's specific function in folate metabolism requires further investigation.

Purpose of the Study:

  • To investigate the role of mitochondrial MTHFD2 in cancer cell survival and its potential as a therapeutic target.
  • To elucidate the mechanism of "folate trapping" toxicity induced by MTHFD2 inhibition.
  • To evaluate the efficacy of targeting MTHFD2 in various cancer types.

Main Methods:

  • Utilized a potent inhibitor (TH9619) targeting dehydrogenase and cyclohydrolase activities.
  • Investigated the impact of the inhibitor on formate flux and folate metabolism.
  • Assessed cancer cell kill in cell lines expressing mitochondrial MTHFD2.

Main Results:

  • Inhibition of mitochondrial MTHFD2 (mTHFD2) by TH9619 leads to "folate trapping" toxicity.
  • mTHFD2 is essential for formate flow to the cytosol, crucial for this toxicity.
  • Cancer cells expressing mTHFD2 are susceptible to TH9619-induced cell death.

Conclusions:

  • Targeting mitochondrial MTHFD2 represents a promising therapeutic strategy for cancers overexpressing this enzyme.
  • The "folate trapping" mechanism offers a novel approach for cancer treatment.
  • Further evaluation in breast, prostate, colorectal, and AML is warranted.