HER2, or Human Epidermal Growth Factor Receptor 2, is a protein located on the surface of human cells. This protein acts like an antenna, receiving signals from outside the cell that instruct it to grow, divide, and repair itself. These functions are fundamental for the normal development and maintenance of all tissues in the body. Understanding HER2’s normal behavior is the first step in recognizing its broader significance in health.
Normal Function of HER2
HER2 is a type of protein known as a receptor tyrosine kinase, which binds signals outside the cell and activates other proteins inside. In its usual state, HER2 forms pairs with other HER family receptors, such as HER1, HER3, or HER4, on the cell surface. This pairing allows the receptor complex to become active and transmit signals inward.
Once activated, these paired receptors initiate a cascade of biochemical reactions within the cell, forming a complex signaling pathway. These internal signals travel to the cell’s nucleus, where they influence gene expression. This normal signaling precisely regulates cell growth, division, and repair, ensuring tissue health and proper organ function.
HER2’s Role in Disease
While HER2 plays a beneficial role in healthy cells, problems arise when its signaling becomes dysregulated, often due to an increased number of HER2 proteins on the cell surface, a condition known as HER2 overexpression or gene amplification. This means a cell produces too many copies of the HER2 gene, leading to an abundance of the HER2 protein. An excess of these receptors results in constant, amplified growth signals, even without external cues.
This continuous signaling pushes the cell into uncontrolled growth and division, leading to rapid tumor formation. This uncontrolled proliferation contributes to the aggressive nature of cancers driven by HER2 alterations.
HER2 overexpression is notably implicated in several types of cancer, with breast cancer being the most recognized example. Approximately 15% to 20% of breast cancers are classified as HER2-positive. Beyond breast cancer, HER2 alterations are also found in other malignancies, including about 10% to 30% of gastric and gastroesophageal junction cancers, and to a lesser extent in some lung, ovarian, and colorectal cancers.
Identifying HER2 Status
Determining a patient’s HER2 status is a necessary step in diagnosing certain cancers, as it guides treatment decisions. Two laboratory tests are used to assess HER2 levels or gene copies.
Immunohistochemistry (IHC) measures the amount of HER2 protein present on the surface of cancer cells in a tissue sample. IHC staining provides a score from 0 to 3+, with scores of 3+ indicating a high level of HER2 protein overexpression. A score of 0 or 1+ suggests low or no HER2 protein, while a 2+ score is considered equivocal and usually requires further testing.
For equivocal cases, or to directly assess gene amplification, Fluorescence In Situ Hybridization (FISH) is often employed. FISH directly counts the number of HER2 gene copies within the cell’s nucleus. This test uses fluorescent probes that bind specifically to the HER2 gene, allowing researchers to visualize and count the gene copies under a microscope. An increased number of HER2 gene copies confirms HER2 gene amplification.
Targeting HER2 in Treatment
When HER2 signaling becomes overactive in cancer, medical treatments are designed to counteract this abnormal activity. These targeted therapies interfere with the HER2 protein or its signaling pathway, aiming to halt uncontrolled cell growth.
One major class of these treatments involves monoclonal antibodies, such as trastuzumab. Trastuzumab works by binding directly to the HER2 receptor on the cancer cell surface, physically blocking it from receiving growth signals. This binding also flags the cancer cell for destruction by the body’s immune system, adding another layer of therapeutic action.
Another approach uses tyrosine kinase inhibitors (TKIs), which are small molecules that enter the cell and block the internal signaling portion of the HER2 receptor. Lapatinib, for instance, inhibits the enzymatic activity of the HER2 receptor from within the cell, preventing it from activating downstream growth pathways. These therapies disrupt the abnormal signaling cascade, leading to a reduction in cancer cell proliferation and improved outcomes for patients with HER2-positive diseases.