The way in which a patient metabolizes folic acid affects the overall prognosis and response to chemotherapy for malignant pleural mesothelioma.
Malignant pleural mesothelioma (MPM) is a rare, aggressive tumor affecting the membranes lining the lungs. Often caused by asbestos exposure, symptoms include shortness of breath, cough, and chest pain due to a build-up of fluid around the lungs. MPM prognosis is grim, with few treatment options and a remission rate of only about 40%. Doctors are investigating ways to improve treatment outcomes.
Folic acid metabolism plays a role in mesothelioma treatment. A study by Fabian Mairinger and colleagues published in Oncotargetexamined genetic markers of folic acid metabolism as a potential predictive biomarker of chemotherapy success. Standard MPM treatment includes chemotherapy using two drugs, pemetrexed and cisplatin. Pemetrexed is an antifolate drug, meaning it blocks the production of folic acid. Folic acid deficiency slows the rapid division and growth of tumor cells. Investigators quantified the expression of three genes involved in the uptake, activation, and metabolism of folic acid using commercially-available gene expression assays and tissue samples taken from 56 patients with MPM. Statistical analysis of the gene expression measurements allowed investigators to categorize patients into low-, intermediate-, and high-risk groups, according to their probability of response to antifolate drug chemotherapy.Observed gene expression levels were significantly associated with disease progression (p=0.0279) and remission (p= 0.0262). Additionally, certain patterns of gene expression were found only in tumors without progression, while others were only seen in progressive cancer cases.
Therefore, incorporating folic acid gene markers into future studies may help improve and individualize MPM treatment. This could potentially save patients who do not respond to antifolate drug treatment from suffering the side effects of ineffective chemotherapy.
Written By: Cindi A. Hoover, PhD
Source: Mairinger FD, Vollbrect C, Flom E, Christoph DC, Schmid K-W, Kollmeier J, Popper HH, Mairinger T, Walter RFH. Folic acid phenotype (FAP) is a superior biomarker predicting response to pemetrexed-based chemotherapy in malignant pleural mesothelioma. 2017. Oncotarget. http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path=16398