What is PIK3CA/mTOR pathway?

Cells throughout the body carry a gene called PIK3CA. This gene is responsible for creating a part of the enzyme called PI3K that oversees cell growth, cell survival, and metabolism. This gene is part of the mTOR pathway.

PIK3CA works like a stoplight for cells on a certain “road” within the cell. When the PIK3CA gene mutates, the enzyme gets overactive and the stoplight stops working. Cells can begin to grow and divide without a signal telling them to stop, leading to a host of problems and chaos. This environment can lead to cancer, and the cancer may be more resistant to treatment. 

A PIK3CA mutation is more commonly found in colon and gastric cancers. 

There are targeted therapies being studied, drugs called “inhibitors,” that block the signals causing cancer cells to grow. 

Also found in the mTOR pathway are tumor surpressor proteins TSC2 and PTEN. These work as brakes and may be dysregulated in neuroendocrine cancers.

How to know if you have a PIK3CA mutation 

Biomarker testing can be run on tumor or blood samples to determine if there’s a mutation in the PIK3CA gene or dysregulation in the mTOR pathway.

Impact on treatment

Gastric/GEJ cancer patients (HER2-positive)

• Some studies show patients have less benefit from trastuzumab (Herceptin) if they have a PIK3CA mutation

Colon and rectal cancer patients

• Research published in the September 2025 New England Journal of Medicine provided strong evidence for colorectal cancer patients with an alteration in the PI3K-pathway gene (including a PIK3CA mutation) taking a daily low dose (160 mg) of aspirin for three years after surgery, showing that it reduced the risk of cancer recurrence by approximately 51-58% in these patients. 

Several trials are looking at therapies for dysregulation and mutations in the mTOR pathway.

Ask your doctor how your biomarker test results are informing your treatment plan and if you qualify for any clinical trials.