JAN 21, 2020 2:57 PM PST

Repurposing Existing Drugs to Treat Cancer

WRITTEN BY: Carmen Leitch

Even after the complicated task of drug development, pharmaceuticals have to be rigorously tested before they can be offered to patients, so it can be much easier to find more than one application for an existing medication. Scientists have now tested a wide variety of drugs that are used to treat many different conditions to see if they had any anti-cancer effect. They were surprised to find that nearly fifty of the ones they assessed, including drugs for alcoholism, diabetes, inflammation, and pet medication for arthritis, exhibited anti-cancer activity that was previously unknown. The work has been reported in Nature Cancer.

"We thought we'd be lucky if we found even a single compound with anti-cancer properties, but we were surprised to find so many," said Professor Todd Golub, chief scientific officer and director of the Cancer Program at the Broad Institute of MIT and Harvard, and Charles A. Dana Investigator in Human Cancer Genetics at Dana-Farber.

This work utilized a collection of around 6,000 drugs that have either been proven to be safe in clinical trials or are approved by the Food and Drug Administration; it's called the Drug Repurposing Hub. The researchers tagged 578 human cancer cell lines with DNA barcodes so the vast number of cells could be pooled and exposed to the many medications. The survival rate of the various cancer cells was measured so the investigators could determine which of the drugs kill cancer.

"We created the repurposing hub to enable researchers to make these kinds of serendipitous discoveries in a more deliberate way," said the first author of the study Steven Corsello, an oncologist at Dana-Farber and founder of the Drug Repurposing Hub.

The researchers discovered the anti-cancer activity of fifty drugs, some of which killed selectively, while others destroyed cancer cells in surprising ways.

"Most existing cancer drugs work by blocking proteins, but we're finding that compounds can act through other mechanisms," said Corsello. Some of these drugs don't work by interfering with a protein; they stabilize a chemical interaction or activate a protein, for example. This cell-survival-based approach made identifying these mechanisms easier, said Corsello.

Image credit: Pixabay

In another case, cancer cells were killed by drugs that interacting with something unknown. For example, tepoxalin is used to treat osteoarthritis in dogs, and this anti-inflammatory medication kills cancer after acting on an unknown target in cells that express high levels of a protein called MDR1.

Genetic characteristics like methylation levels and mutations in the cancer cell lines enabled the researchers to predict which drugs would kill them. For example, cells that carried mutations that reduced their metallothionein protein levels were killed by a drug for alcohol dependence, called Antabuse. If cells expressed a certain sulfate transporter called SLC26A2, they were susceptible to drugs that contain vanadium.

"The genomic features gave us some initial hypotheses about how the drugs could be acting, which we can then take back to study in the lab," said Corsello. "Our understanding of how these drugs kill cancer cells gives us a starting point for developing new therapies. This is a great initial dataset, but certainly, there will be a great benefit to expanding this approach in the future."

Sources: AAAS/Eurekalert! via Broad Institute of MIT and Harvard, Nature Cancer

About the Author
  • Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
OCT 25, 2021
Space & Astronomy
Spaceflight Seems to Raise Levels of Circulating Cell-Free Mitochondrial DNA
OCT 25, 2021
Spaceflight Seems to Raise Levels of Circulating Cell-Free Mitochondrial DNA
Spaceflight is being marketed as a tourist opportunity for extremely wealthy people, and lengthy space missions that cou ...
NOV 01, 2021
Cell & Molecular Biology
Is This Closed Barrier Why Psychiatric & Bowel Disorders are Linked?
NOV 01, 2021
Is This Closed Barrier Why Psychiatric & Bowel Disorders are Linked?
Inflammatory bowel disease (IBD) is a term that describes chronic gut inflammation and includes ulcerative colitis and C ...
NOV 02, 2021
Cell & Molecular Biology
Amino Acid Supplements May Prevent Neuronal Death & Dementia
NOV 02, 2021
Amino Acid Supplements May Prevent Neuronal Death & Dementia
Dementia is an umbrella term for several age-related disorders that can cause cognitive problems such as dysfunction in ...
NOV 05, 2021
Genetics & Genomics
Solution to a Pigeon Genetic Mystery Provides Insight Into Development
NOV 05, 2021
Solution to a Pigeon Genetic Mystery Provides Insight Into Development
This photo by Sydney Stringham shows the domestic pigeons that were bred by the researchers for this research.
NOV 12, 2021
Health & Medicine
T-Cell Signature Distinguishes COVID-19 Immunity from Other Respiratory Infections
NOV 12, 2021
T-Cell Signature Distinguishes COVID-19 Immunity from Other Respiratory Infections
COVID-19 is a highly studied disease. It’s caused the most significant influx of research papers in a single year& ...
NOV 23, 2021
Clinical & Molecular DX
Stopping COVID False-Positives From Slipping Through the Cracks
NOV 23, 2021
Stopping COVID False-Positives From Slipping Through the Cracks
False-positive COVID tests results—where the patient isn’t infected but receives a positive result—tri ...
Loading Comments...