New York, NY July 07: Researchers at the Mount Sinai Tisch Cancer Center have identified a previously underrecognized folate deficiency that may cause severe anemia in some patients receiving PARP inhibitors, a widely used class of targeted cancer therapies.
Their findings, published in the latest issue of the journal Blood Red Cells & Iron (Blood RCI) (doi.org/10.1016/j.brci.2026.100052), suggest that routine screening and treatment with folic acid could help many patients avoid blood transfusions, hospitalizations, and interruptions to their cancer treatment.
PARP inhibitors are used to treat multiple cancers, including ovarian, breast, prostate, and pancreatic cancers associated with BRCA gene mutations. While these drugs have transformed treatment options for many patients, they commonly cause anemia, a condition in which the body does not have enough healthy red blood cells to carry oxygen throughout the body. Severe anemia can cause extreme fatigue, shortness of breath, and dizziness, and may force physicians to reduce treatment doses or interrupt therapy.
Until now, many oncologists assumed anemia caused by PARP inhibitors was mainly due to a drug class effect that causes bone marrow suppression. This study suggests that a significant portion of patients instead may develop severe folate deficiency in association with PARP inhibitors, which can be diagnosed with a simple blood test and treated with an inexpensive oral vitamin (folic acid). Folic acid helps the body form healthy red blood cells. Folate is essential for producing healthy red blood cells and supporting normal cell growth throughout the body.
“Our study challenges the long-held belief that anemia from PARP inhibitors is simply an unavoidable side effect of treatment,” said corresponding author Noa Rippel, MD, Chief Fellow in Hematology and Medical Oncology at the Icahn School of Medicine at Mount Sinai and incoming faculty member at the Mount Sinai Tisch Cancer Center. “We found that a significant number of patients receiving PARP inhibitor treatment developed a new and severe folate deficiency, which led to clinically significant anemia. This condition is easy to diagnose and inexpensive to treat. Identifying this deficiency early could help patients stay on their cancer therapy while avoiding unnecessary complications.”
This is the first study to systematically evaluate folate deficiency in patients receiving PARP inhibitors. Previous reports had been limited to individual case studies.
The researchers reviewed the records of 512 patients with BRCA-mutated cancers treated with PARP inhibitors. They found that 3.1 percent developed folate deficiency anemia, more than six times the estimated rate seen in the general population. Nearly 30 percent of patients also developed unexplained macrocytic anemia, a condition marked by unusually large red blood cells which is commonly associated with folate deficiency, suggesting that many additional cases may have remained undiagnosed.
More than 60 percent of patients with folate deficiency anemia required blood transfusions, many were hospitalized, and twelve of sixteen (75 percent) experienced interruptions in their cancer treatment.
The encouraging finding was that folate deficiency in association with PARP inhibition was readily treated. Patients who received oral folic acid supplements recovered their folate levels and anemia, allowing them to safely resume their PARP inhibitor therapy. The researchers also found evidence suggesting that starting folic acid supplements when PARP inhibitor treatment begins may help prevent this complication.
“These findings have the potential to change how oncologists evaluate anemia in patients taking PARP inhibitors,” Dr. Rippel said. “A simple blood test and an inexpensive vitamin supplement may help improve patients’ quality of life, reduce health care costs, and help patients remain on treatments that can extend survival.”
As PARP inhibitors continue to be approved for more types of cancer, the researchers believe greater awareness of folate deficiency could benefit many thousands of patients annually. The investigators hope the findings will inform future clinical guidelines and encourage routine monitoring of folate levels during treatment.
Statistical support for the study was provided by the Mount Sinai Tisch Cancer Center.