In the fight against ovarian cancer, folate receptor alpha (FRα or FR-alpha), a biomarker found on the surface of some ovarian cancer cells, is helping open the door to a new generation of targeted therapies.
“At City of Hope, we're at the forefront of new ways to target FRα-positive ovarian cancer," says Joshua G. Cohen, M.D., the medical director of the gynecologic cancer program at City of Hope Orange County. “One group that may particularly benefit from FRα-targeted therapies is patients with platinum-resistant ovarian cancer — ovarian cancer that has returned or is no longer responding to traditional platinum-based chemotherapy.”
Dr. Cohen answers some of the most common questions patients have about FRα-positive ovarian cancer and emerging treatment options.
What does it mean if ovarian cancer is FRα-positive?
When ovarian cancer is FRα-positive, it means the cancer cells have elevated levels of a protein called folate receptor alpha on their surface. That protein can serve as a target for certain antibody-based therapies known as antibody-drug conjugates (ADCs).
Why is FRα testing important?
FRα testing gives us valuable information that can help guide treatment decisions. There are specific expression levels for FRα which we use to determine if certain therapies will benefit patients. For example, an expression level of 75% means that within the tumor, 75% of the cancer cells express the FRα receptor.
Testing is performed on tumor tissue using an FDA-approved diagnostic that measures FRα expression levels. Researchers are also studying whether these therapies may benefit patients earlier in their treatment journey, including those whose cancers remain sensitive to platinum-based treatments.
There is data that use of ADCs in the platinum-sensitive setting (meaning the tumor may still respond to platinum treatments) may also benefit patients. Ongoing clinical trials will assess whether using these type of therapies earlier in the treatment course for ovarian cancer patients will improve outcomes.
What are antibody-drug conjugates (ADCs)?
Think of an ADC as a precision delivery system. The antibody portion recognizes and binds to cancer cells carrying a specific target, such as FRα, and then releases its chemotherapy payload inside the cell. Traditional chemotherapy, by contrast, circulates throughout the body.
Because ADCs are designed to deliver treatment more precisely, patients often experience less systemic side effects than they would with conventional chemotherapy agents.
What side effects can occur with FRα-targeted therapies?
As with any cancer treatment, ADCs can cause side effects. The most common include eye-related symptoms such as blurry vision, neuropathy (nerve damage), nausea and diarrhea.
In clinical practice, these side effects are typically manageable with standard-of-care therapies, allowing many patients to continue treatment safely.
Vision-related side effects are typically temporary and almost always resolve within two weeks after treatment is stopped. Patients should let their care team know promptly about any new symptoms or side effects so they can be addressed.
What questions should patients ask their care team about FRα testing and treatment options?
We encourage patients to have open conversations with their care team about biomarker testing and treatment options. Some questions to consider include:
- Has my tumor been tested for FRα?
- What were the results of that testing?
- Am I a candidate for an FRα-targeted therapy?
- Are there clinical trials that might be appropriate for me?
- What side effects should I expect, and how can they be managed?
These discussions can help patients better understand whether newer targeted therapies may play a role in their treatment plan and make the decisions that are right for them.
What emerging treatments are in clinical trials?
New approaches being studied at City of Hope and other leading academic cancer centers include next-generation ADCs, CAR T cell therapies, and vaccines that help the immune system recognize cancer. These strategies reflect a broader effort to improve precision and expand options for patients, particularly in cases where standard treatments are no longer effective.
Can combination therapies be utilized to treat FRα-positive ovarian cancer?
We have seen clinically meaningful benefits in combining FRα-targeted therapy with other target specific agents, drugs like bevacizumab that block the growth of new blood vessels that tumors depend on to grow and spread, and PARP inhibitors, which are drugs that prevent cancer cells from repairing their DNA.
These combinations work by pairing targeted therapy with treatments that damage cancer cells, block their blood supply or activate the immune system. Side effects vary depending on the treatment combination but may include fatigue, low blood counts, eye symptoms or immune-related effects, all of which are carefully monitored and managed by the care team.
We are still actively studying novel combinations with ADCs that target FRα. This category of drugs represents an exciting new paradigm in the treatment of ovarian cancer.
Also read:
Talking Hope: What every woman should know about gynecologic cancers
City of Hope Orange County physician-scientists advance clinical research in gynecologic oncology
Grateful ovarian cancer patient is back on the road to tomorrow
Ovarian cancer no match for swift action by City of Hope Orange County team