Study pinpoints malignant mesothelioma patients likely to benefit from drug pemetrexed

August 29, 2012

Previous studies have hypothesized that low levels of the enzyme thymidylate synthase (TS) likely mark patients who will benefit from the drug pemetrexed – but results have been inconclusive at best and at times contradictory. A University of Colorado Cancer Center study recently published in the Journal of Thoracic Oncology provides an explanation why: only in combination with high levels of a second enzyme, FPGS, does low TS predict response to pemetrexed in patients with malignant pleural mesothelioma.

"The hope is that oncologists could test a patient for TS and FPGS levels and so discover if the patient should be treated with or if another therapy might be more appropriate," says the paper's first author, Daniel C. Christoph, MD, PhD, medical oncologist at the West German Cancer Center, working as an international in the lab of CU Cancer Center investigator, Fred Hirsch, MD, PhD.

Pemetrexed works by inhibiting the enzyme TS, which cancer cells need in order to replicate their DNA. So it stands to reason that tumors already low in TS would be most affected by the drug – blocking the remaining TS would effectively stop the ability of to synthesize new DNA. However, Christoph and colleagues tested 84 samples of mesothelioma in which patients had been treated with pemetrexed and found that low levels of TS only in combination with concurrently high levels of FPGS predicted patients' response to the drug.

The study also explained the mechanism by which FPGS increases the clinical effectiveness of pemetrexed:

"High levels of FPGS allow pemetrexed to stay longer inside cells, giving the drug longer to work against TS," Christoph says. Of the samples tested, patients with low TS and high FPGS had more response to pemetrexed and longer durations of survival.

According to Christoph, the current study provides the preclinical work needed to justify exploring the predictive power of TS and FPGS in mesothelioma patients. A prospective observational study of these biomarkers could lead to their wide use in predicting patients' response to pemetrexed.

Explore further: Lung cancer ALK rearrangement may predict pemetrexed efficacy, study shows

Related Stories

Lung cancer ALK rearrangement may predict pemetrexed efficacy, study shows

September 1, 2011
Patients with ALK-rearranged non-small cell lung cancer (NSCLC) responded significantly better to pemetrexed (brand name: Alimta) than patients whose cancer did not show ALK translocation, according to research published ...

Recommended for you

Shooting the achilles heel of nervous system cancers

July 20, 2017
Virtually all cancer treatments used today also damage normal cells, causing the toxic side effects associated with cancer treatment. A cooperative research team led by researchers at Dartmouth's Norris Cotton Cancer Center ...

Molecular changes with age in normal breast tissue are linked to cancer-related changes

July 20, 2017
Several known factors are associated with a higher risk of breast cancer including increasing age, being overweight after menopause, alcohol intake, and family history. However, the underlying biologic mechanisms through ...

Immune-cell numbers predict response to combination immunotherapy in melanoma

July 20, 2017
Whether a melanoma patient will better respond to a single immunotherapy drug or two in combination depends on the abundance of certain white blood cells within their tumors, according to a new study conducted by UC San Francisco ...

Discovery could lead to better results for patients undergoing radiation

July 19, 2017
More than half of cancer patients undergo radiotherapy, in which high doses of radiation are aimed at diseased tissue to kill cancer cells. But due to a phenomenon known as radiation-induced bystander effect (RIBE), in which ...

Definitive genomic study reveals alterations driving most medulloblastoma brain tumors

July 19, 2017
The most comprehensive analysis yet of medulloblastoma has identified genomic changes responsible for more than 75 percent of the brain tumors, including two new suspected cancer genes that were found exclusively in the least ...

Novel CRISPR-Cas9 screening enables discovery of new targets to aid cancer immunotherapy

July 19, 2017
A novel screening method developed by a team at Dana-Farber/Boston Children's Cancer and Blood Disorders Center—using CRISPR-Cas9 genome editing technology to test the function of thousands of tumor genes in mice—has ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.