Low-grade serous ovarian cancer (LGSOC) is a rare, slow-growing type of cancer. While it's often a challenge to diagnose and treat, researchers have made progress in understanding and treating LGSOC over the past decade.
"As we gain more and more information about individual tumors and the best ways to target them, it gives us so many more options to personalize care and to give our patients more treatments to live longer," says Rachel N. Grisham, MD, a gynecologic medical oncologist at Memorial Sloan Kettering Cancer Center in West Harrison, New York.
Understanding LGSOC
Identifying the genetic makeup of an LGSOC tumor can provide a key to slowing or stopping its spread. For instance, Grisham says, studies have shown that alterations affecting a genetic pathway known as MAP kinase occur in more than 60% of low-grade serous ovarian cancers.
The MAP kinase (MAPK) pathway is a string of proteins that control crucial tasks like cell division and cell death. The most common mutation in LGSOC is in the KRAS gene. This gene is essential for telling your cells when to grow and when to stop. But if it doesn't work the way it should, cell growth gets stuck in the "on" position.
Learning about the genetic drivers behind LGSOC helps researchers identify promising new treatment targets and develop new treatments. It can also help doctors choose the best treatment for your particular LGSOC. That's why after you're diagnosed with LGSOC, it's recommended to get genetic testing. Genetic testing for LGSOC has two main types:
Genetic (germline) testing. It looks for genetic changes in the DNA you were born with, and that are present in each of your cells.
Somatic or tumor testing. A small piece of your tumor is removed and looked at under a microscope. This allows doctors to check for mutations present only in the tumor.
"All of our national guidelines recommend that we do routine germline and somatic tumor testing on all ovarian cancer patients," Grisham says.
Advances in LGSOC Treatments
Your LGSOC treatment will depend, in part, on the stage of your cancer at the time of diagnosis. Some cancers in early stages may be treated with surgery alone.
"Unfortunately, the majority of our patients have advanced stage disease when they're first diagnosed," Grisham says.
After surgery to remove as much of the cancer as possible, the standard of care is chemotherapy. But unlike other types of ovarian cancer, LGSOC usually doesn't respond well to chemotherapy. The reason is that LGSOC cells divide slowly, and chemotherapy is best at treating quickly dividing cancer cells.
Researchers keep searching for other ways to treat low-grade serous ovarian cancer. These include:
Targeted therapies
These medications target the proteins that cancer cells rely on to grow and spread.
In 2025, a targeted therapy became the first ever FDA-approved treatment specifically for LGSOC. It's a combination of two pills: avutometinib and defactinib (Avmapki Fakzynja Co-Pack). Here's how it works:
Avutometinib can block the MAPK pathway. That helps cancer cells stop growing.
Defactinib targets a second pathway, known as the focal adhesion kinase (FAK) pathway. That helps to prevent cancer cells from developing treatment resistance.
In a clinical trial of this treatment combination:
- 44% of people with LGSOC saw their tumor decrease in size or go away.
- The average response lasted more than 31 months.
- People had fewer side effects than from chemotherapy.
Avutometinib plus defactinib is only approved for use if you have:
- A KRAS mutation
- Already tried another cancer treatment
- Cancer recurrence (cancer that's come back)
The hope is that more targeted treatments for LGSOC will come. "We're trying to identify new targeted therapies that may be beneficial for patients with low-grade serous ovarian cancer," says Grisham.
Endocrine combination therapies
Most people with LGSOC are "estrogen receptor positive," which means that your cancer cells depend on estrogen to grow and spread. Because of that, hormone therapy may have a big role to play in treating it. Since 70% of all breast cancer cases are also estrogen receptor positive, "we can learn a lot from our breast cancer colleagues," says Grisham.
For instance, one study found that two FDA-approved breast cancer treatments were able to delay how fast LGSOC progressed.
Ribociclib is a drug known as a CDK4/6 inhibitor. It stops overactive CDK4/6 proteins, which cause cancer cells to grow out of control.
Letrozole is an aromatase inhibitor. It blocks an enzyme called aromatase that helps your body make estrogen. Less estrogen means less "fuel" for cancer cells.
Of the 48 people with recurrent low-grade serous ovarian cancer who were part of the study, 56% saw their tumor size stabilize during treatment. And the tumors of 23% of the people in the study shrank.
More endocrine combination therapies could be on the way.
Antibody-drug conjugates (ADCs)
Antibody-drug conjugates bind to a protein on the surface of cancer cells. Then, they deliver a payload – typically a chemotherapy drug – straight to the cells. The idea is that this targets cancer cells while sparing healthy cells.
"[ADCs] are a huge thing across every type of solid tumor right now," Grisham says.
In 2024, mirvetuximab soravtansine-gynx (Elahere) became the first ADC approved as a general ovarian cancer treatment. It may take years to figure out the best way to use it. In the meantime, more ADCs are in development, some of which may hold promise for treating LGSOC.
Advances in LGSOC Diagnosis
Low-grade serous ovarian cancer is a challenge to diagnose. That's partly because it's so rare, making up less than 10% of all ovarian cancers. LGSOC symptoms, like bloating, belly pain, and feeling full quickly, also overlap with the symptoms of many other conditions. For these reasons, the condition is often not found until it's in an advanced stage, which makes it much harder to treat.
"This is not usually something that runs in families … so it can be really difficult to identify patients," Grisham says.
Ongoing research is trying to find new ways to detect LGSOC sooner, including blood-based biomarkers, molecules in your blood that may signal the presence of LGSOC. If so, a simple blood test may one day provide a diagnosis.
"That would be a huge step forward if we could identify a good screening strategy to diagnose this at an earlier stage," Grisham says.
Hope on the Horizon
Grisham is optimistic about the future of LGSOC treatment.
"I do think in 10 years, we'll have a large number of individualized, personalized, molecularly targeted treatments where we'll be able to make informed decisions based not only on the mutations of a cancer cell, but also the proteins that are expressed by that cancer cell," she says.
Because the proteins in cancer cells can change in response to different treatments and also over time, retesting tumor samples during and after treatment may provide valuable insight. "We're learning more about the dynamic changes that happen in cancer cells over time," Grisham says, "and that is going to help us to better personalize and direct therapy."
As more effective LGSOC treatments are developed, doctors will face a new challenge: Figuring out the most helpful order in which to give them. "Sequencing was never really a problem when you had limited options available," Grisham says. "But … it's a great problem to have."
