PIK3CA


PIK3CA is a gene that provides instructions for making a protein called p110α. This protein is part of the PI3K family, which plays a central role in controlling how cells grow, divide, and survive. When PIK3CA is working normally, it helps maintain balance in these processes. When it is mutated, the pathway can become overactive and drive cancer growth.

What does the PIK3CA protein do?

The p110α protein, produced by PIK3CA, is part of the PI3K/AKT/mTOR pathway, which functions as a communication system within the cell. This pathway tells cells when to grow, survive, and repair themselves. In normal cells, this signal is tightly controlled. In cancer, mutations in PIK3CA can cause the pathway to become too active, leading to uncontrolled growth.

Where is PIK3CA active in the body?

PIK3CA is active in many types of normal cells throughout the body. Because it is part of a basic communication pathway, it is present in most tissues where cells need to grow and divide.

How is PIK3CA altered in cancer?

In cancer, the PIK3CA gene is often changed by mutations. These mutations make the protein too active. Most occur in two “hotspots” of the gene called exon 9 and exon 20. The most common changes are named E542K, E545K, and H1047R, and they account for more than half of all PIK3CA mutations across cancers. Rare inherited changes in PIK3CA can also cause PIK3CA-related overgrowth syndromes (PROS), where certain body parts grow much larger than normal.

How do pathologists test for PIK3CA?

Pathologists can test for PIK3CA mutations using tumor tissue. Methods include:

How are PIK3CA results reported and what do they mean?

When PIK3CA testing is performed, the results show whether a mutation was found and provide details if one is present.

  • No mutation detected: The tumor does not show changes in PIK3CA, meaning it is not being driven by this gene.

  • Mutation detected: The report will usually list the exact mutation, such as E545K or H1047R. These results mean the tumor is using the PI3K pathway to grow, which may influence treatment.

  • Variants of uncertain significance: Sometimes, changes are found that are not yet clearly linked to cancer behavior. These results may require further study.

The interpretation of these results depends on the cancer type and treatment options available, including targeted drugs like alpelisib.

What types of tumors show PIK3CA mutations?

PIK3CA is one of the most frequently mutated genes in cancer. It has been studied in many tumor types, and in some it is very common.

  • Endometrial cancer: Nearly half of endometrial carcinomas have PIK3CA mutations. These mutations help drive tumor growth by keeping the PI3K/AKT pathway turned on.

  • Breast cancer: About one-third of breast cancers have PIK3CA mutations, especially hormone receptor–positive and HER2–negative cancers. Patients with these mutations may benefit from targeted therapies such as alpelisib.

  • Cervical cancer: Around one-quarter of cervical cancers carry PIK3CA mutations. These are often seen in squamous cell carcinomas and can influence tumor behavior.

  • Colorectal cancer: Between 15% and 20% of colorectal cancers have PIK3CA mutations. These cancers may respond differently to some treatments, including aspirin, which has shown promise in improving survival.

  • Bladder cancer: Roughly 20% of bladder cancers show mutations in PIK3CA. These changes contribute to tumor growth but also open the door to pathway-targeted therapies being tested in clinical trials.

  • Ovarian cancer: About 10% of ovarian cancers have PIK3CA mutations, particularly in clear cell and endometrioid subtypes.

  • Lung cancer: Around 5–6% of non-small cell lung cancers show PIK3CA mutations, usually alongside other genetic changes.

Why is PIK3CA important in cancer?

Knowing whether a tumor has a PIK3CA mutation is important for diagnosis, prognosis, and treatment planning.

For example:

  • In breast cancer, patients with a PIK3CA mutation may be treated with alpelisib, a drug that blocks the PI3K pathway.

  • In colorectal cancer, PIK3CA mutations may affect which treatments are most effective and may help predict benefit from aspirin use.

  • In other cancers, the presence of a PIK3CA mutation may indicate the tumor is more aggressive or more likely to return after treatment.

Can aspirin help if PIK3CA is mutated?

Research suggests that patients with colorectal cancer whose tumors carry PIK3CA mutations may benefit from regular low-dose aspirin after diagnosis. Studies show aspirin use in these patients may lower the risk of cancer coming back and improve overall survival. The effect is strongest for mutations in the PI3K pathway, including PIK3CA. This is an active area of research and not yet standard for all patients. Anyone considering aspirin should first discuss the risks and benefits with their doctor.

Questions to ask your doctor

  • Was my tumor tested for PIK3CA?

  • Did the results show a mutation, and if so, which one?

  • How does this result affect my treatment plan?

  • Could aspirin therapy or targeted therapy apply to me?

  • Should my family be tested for inherited PIK3CA changes?

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