While there’s no cure for PIK3CA-related overgrowth spectrum, treatment ranging from medications to surgery can help manage symptoms.
PIK3CA-related overgrowth spectrum (PROS) represents a collection of diverse disorders caused by changes in the PIK3CA gene. This gene is responsible for regulation of cell growth and division, and the genetic changes that occur in PROS result in enlargement of various tissues throughout the body.
There are several types of PROS, defined based on the tissues that are affected. Affected tissues may include fat, muscle, or bone, as well as blood vessels and the brain.
There’s no cure for PROS, and treatment is based mainly on the management of symptoms. Symptoms vary from person to person based on PROS type and the affected tissues, so an individualized approach to care is needed.
Depending on how PROS affects the body, treatment plans for PROS may
- laser ablation
- assistive devices, such as wheelchairs, walkers, braces, or shoe lifts
- physical, occupational, or speech therapy
Learn more about the various treatment options for PROS, including when these options may be considered.
Most medications used in the treatment of PROS are intended to manage the symptoms or complications of disease. Since symptoms vary based on PROS type and presentation, not all people with PROS will receive the same medications.
Some types of medications commonly used to treat symptoms and complications of PROS
- anticoagulant therapy, such as blood thinners, to prevent blood clots
- antiseizure medications
- growth hormone therapy
- antibiotics, in people with lymphoid complications
Specialists are often involved in the management of PROS symptoms and complications and may prescribe additional medications. These may include medications to
- kidney problems
- heart problems
- movement problems or decreased muscle tone
- behavioral or psychiatric disorders
For people with severe symptoms of PROS, targeted therapy may be recommended. Targeted therapy involves the use of medications to treat the underlying causes of disease. In PROS, that involves blockage of signaling pathways that are made overactive by alterations in the PIK3CA gene.
The only targeted therapy currently approved for use in PROS is alpelisib (Vijoice), which inhibits the activity of the PI3K protein that is altered. In clinical studies of alpelisib, treatment was found to
- congestive heart failure
- body enlargement
Alpelisib is currently available for adults and children at least 2 years of age with severe complications from PROS. It may also be used to help manage symptoms in other people with PROS through an expanded, compassionate use program.
Surgery may be used to manage a variety of complications from PROS. Surgeries include:
- Debulking surgery: This may be performed to reduce overgrowth of various body parts if mobility or functionality is limited or if the overgrowth is painful. Debulking surgery may also be performed to remove fatty masses that are affecting the function of organs or nerves.
- Brain surgery: This may be needed to manage neurological complications like seizures or correct abnormalities in brain structure.
- Orthopedic surgery: This may be done to correct skeletal abnormalities that are painful or make it difficult to function. These include removal of extra digits (fingers or toes), closing of growth plates, or correction of structural problems in bones.
Laser ablation surgery may also be considered to correct blood vessel abnormalities in the skin. This involves the use of a high-energy laser to remove abnormal cells and may represent a less invasive treatment option for these types of symptoms. If blood vessel problems occur deeper in the body, more traditional surgical approaches may be needed instead.
Before alpelisib was approved for use in PROS, it was used as an
A formal clinical trial is now underway to study the effects of alpelisib treatment in adults and children at least 2 years of age, including those without severe disease. This study may help to increase the number of people who are eligible for alpelisib treatment and improve access to the drug.
Another drug, miransertib, is also being studied for the treatment of PROS.
Miransertib is not currently approved for any other conditions and is only available through a clinical trial program.
The outlook with PROS varies depending on the types of tissues that are affected and the severity of symptoms. In general, people who have brain enlargement — often leading to severe seizures, cognitive or developmental problems, or nerve problems — tend to have worse outcomes than those without brain involvement.
The progression of symptoms also varies based on PROS type. Some symptoms may be progressive and get worse with age, whereas others may stabilize as children get older.
In some cases, if overgrowth of various tissues gets worse, it may lead to other complications such as mobility problems, seizures, or difficulty completing day-to-day activities. In such cases, new treatments may be added to the care plan to help manage these new symptoms.
PROS is a collection of conditions characterized by overgrowth of diverse tissue types, which can lead to a wide range of symptoms. Treatment of PROS is currently based on management of these symptoms, which means that an individualized approach is needed.
PROS care plans may involve a variety of treatment options — including medications and surgeries — to manage symptoms, and a team of specialists to coordinate these treatments.
Targeted therapy with alpelisib is now available for some people with PROS to help target the underlying drivers of overgrowth that cause symptoms.
Additional clinical trials are currently underway that may expand the use of this medication and others like it to increase treatment options for people with various types of PROS.