Genes are instructions within our cells that dictate how our bodies develop and function. Changes in these genetic instructions, known as mutations, can affect gene function and lead to various health implications.
The PIK3CA Gene: Normal Function
The PIK3CA gene contains instructions for creating a protein subunit called p110α, a component of the enzyme phosphatidylinositol 3-kinase (PI3K). PI3K plays a central role in the PI3K/Akt/mTOR pathway. This pathway regulates cellular processes like growth, division, and survival. PI3K’s normal function ensures cells proliferate and survive only when appropriate signals are received.
Understanding PIK3CA Mutations
A PIK3CA mutation changes the gene’s instructions, leading to an altered p110α protein. These changes often result in a “gain-of-function,” making the protein overactive. Instead of acting as a regulated switch, the mutated PIK3CA protein is constantly “on,” continuously signaling for cell growth and division. Common mutations include E542K and E545K in exon 9, and H1047R in exon 20. These are somatic mutations, acquired during a person’s lifetime rather than inherited.
Role of PIK3CA Mutations in Cancer
The constant “on” signaling from a mutated PIK3CA protein significantly contributes to cancer development. This uncontrolled activity promotes unchecked cell proliferation and reduces normal cell death, leading to tumor formation and growth. PIK3CA mutations are among the most common genetic alterations identified across various human cancers. They are frequently observed in types like breast, colorectal, and endometrial cancer. The presence of these mutations can influence how a cancer behaves and progresses.
Targeting PIK3CA Mutations in Treatment
Because PIK3CA mutations drive cancer growth, they serve as targets for specific treatments. This approach, known as targeted therapy, uses medications designed to interfere with the mutated protein’s activity. These drugs, called PI3K inhibitors, block the overactive signaling pathway. Alpelisib, for example, is approved for certain breast cancers harboring PIK3CA mutations. Identifying the PIK3CA mutation in a patient’s tumor helps guide oncologists in selecting treatment strategies, allowing for a more personalized approach to cancer care.
Detecting PIK3CA Mutations
Detecting PIK3CA mutations involves specific testing procedures. This process, often called biomarker testing or molecular profiling, analyzes tumor samples obtained through a biopsy. Liquid biopsies, analyzing blood samples for circulating tumor DNA, offer a less invasive detection method. Techniques like next-generation sequencing (NGS) are commonly used to identify these mutations, providing valuable information about a patient’s tumor genetic makeup and aiding informed treatment decisions.