A HER2 antibody is a type of targeted cancer therapy. These treatments use monoclonal antibodies, which are laboratory-produced molecules engineered to act as substitute antibodies. They are designed to identify and attach to the HER2 protein on the surface of cancer cells. By seeking out this specific marker, these treatments can attack cancer cells more directly than traditional chemotherapy. The development of HER2 antibodies has changed the treatment for patients whose tumors have high levels of the HER2 protein.
Understanding HER2 and Cancer
Human Epidermal Growth Factor Receptor 2 (HER2) is a protein on the surface of cells that helps regulate their growth and division. In healthy cells, HER2 receptors are part of normal signaling pathways that tell cells when to grow, divide, and repair themselves. This process is tightly controlled. However, a faulty HER2 gene can lead to an overproduction of these receptors.
A cancer is “HER2-positive” when its cells have an excessive number of HER2 protein receptors. This is caused by gene amplification, where there are too many copies of the HER2 gene in the cancer cells. The excess receptors constantly signal the cells to grow and divide uncontrollably, often leading to a more aggressive disease.
Diagnosing a HER2-positive cancer is done after a biopsy. Pathologists use specific tests to determine the tumor’s HER2 status. One common method is Immunohistochemistry (IHC), which measures the amount of HER2 protein on the cancer cells. Another test, Fluorescence In Situ Hybridization (FISH), counts the copies of the HER2 gene within the cells. These results guide oncologists in selecting the most effective treatment plan.
Mechanism of HER2 Antibody Therapies
HER2 antibody therapies combat cancer through several mechanisms. The most direct action is blocking growth signals. A monoclonal antibody like trastuzumab binds to the HER2 protein on the cancer cell’s surface. This binding obstructs the receptor, preventing it from receiving signals that tell the cell to grow, which slows or halts tumor growth.
These antibodies also harness the patient’s immune system. When an antibody attaches to HER2 receptors, it acts as a flag marking the cancer cell for destruction. This process, known as antibody-dependent cell-mediated cytotoxicity (ADCC), alerts immune cells like natural killer cells. The immune cells then bind to the antibody and release substances that kill the cancer cell.
An antibody-drug conjugate (ADC) combines a HER2 monoclonal antibody with a potent chemotherapy drug. The antibody acts as a delivery vehicle, attaching to HER2-positive cancer cells. Once the ADC binds to the receptor, it is taken inside the cell where the chemotherapy agent is released. This targeted delivery damages cancer cells while reducing exposure to healthy cells and minimizing side effects. Examples include ado-trastuzumab emtansine (T-DM1) and fam-trastuzumab deruxtecan (T-DXd).
Types of Cancers Treated
The primary application for HER2 antibody therapies is treating breast cancer, as 15-20% of cases are HER2-positive. Therapies like trastuzumab are used for both early-stage and advanced HER2-positive breast cancer. They can be given with chemotherapy before surgery (neoadjuvant) to shrink tumors or after surgery (adjuvant) to reduce the risk of recurrence.
HER2-targeted therapies are also approved for other cancers. Certain stomach (gastric) and esophageal cancers that overexpress the HER2 protein respond to these treatments. For example, trastuzumab combined with chemotherapy can improve survival rates in patients with HER2-positive metastatic gastric or gastroesophageal junction cancer.
Research is exploring HER2-targeted treatments in other cancers with HER2 overexpression. Clinical trials are investigating their use in tumors like certain types of ovarian and bladder cancers. As the understanding of cancer genetics expands, this targeted approach may benefit more patients.
Administration and Potential Side Effects
HER2 antibody therapies are most commonly administered intravenously (IV) in a clinical setting. The infusion into a vein can take 30 to 90 minutes. For some breast cancer treatments, a subcutaneous (under the skin) injection is a quicker alternative. Treatment schedules vary but are often once every few weeks.
Common side effects can occur during or shortly after the infusion, including fever, chills, nausea, and fatigue. These infusion-related reactions are typically most pronounced during the first treatment and can be managed with medication. Headaches and mild rashes are also reported by some patients.
A potential side effect is cardiotoxicity, or damage to the heart muscle. Since HER2 receptors are also on heart cells, blocking them can sometimes weaken the heart’s ability to pump blood effectively, which can lead to congestive heart failure in some cases. To mitigate this risk, a patient’s heart function is evaluated before treatment begins using an echocardiogram or MUGA scan. This monitoring continues regularly throughout therapy, and treatment may be paused or stopped if any decline in heart function is detected.