Anti-HER2 antibody therapies are a form of targeted treatment designed to act on specific types of cancer cells. These treatments are engineered to identify and interfere with a protein that is produced in excessive amounts in certain cancers, driving tumor growth. Unlike traditional chemotherapy that affects all rapidly dividing cells, these antibody therapies are more selective. This focused approach to cancer treatment stems from understanding the molecular signals that cause some cancers to spread.
The Role of HER2 in Cancer
Human Epidermal growth factor Receptor 2 (HER2) is a protein on the surface of cells involved in normal cell growth. The HER2 gene provides instructions for making this protein, which acts as a receptor for signals that tell the cell to divide. In a healthy cell, these signals are tightly regulated to ensure cells grow only when needed.
In some cancers, a genetic mutation causes gene amplification, where the HER2 gene creates too many copies of itself. This leads to an overproduction, or overexpression, of the HER2 protein on the cancer cell’s surface. With an abnormally high number of these receptors, cancer cells receive constant signals to grow and divide uncontrollably, leading to tumor formation. Cancers with this characteristic are known as HER2-positive and are often more aggressive.
To determine if a cancer is HER2-positive, pathologists analyze a tumor tissue sample using two primary tests: Immunohistochemistry (IHC) and Fluorescence In Situ Hybridization (FISH). The IHC test measures the amount of HER2 protein, assigning a score from 0 to 3+. A score of 3+ is HER2-positive, 0 or 1+ is negative, and a borderline score of 2+ requires a follow-up FISH test. The FISH test examines the cancer cells’ genes to count the number of HER2 gene copies, confirming if gene amplification is present.
Mechanism of Anti-HER2 Antibodies
Anti-HER2 antibodies are laboratory-produced molecules known as monoclonal antibodies. They are engineered to specifically recognize and bind to the HER2 protein on the exterior of cancer cells. This binding action is highly specific, much like a key fitting into a particular lock, allowing the treatment to single out cancer cells that overexpress the HER2 protein while largely sparing healthy cells.
Once attached to the HER2 protein, the antibody works in two primary ways. The first is to physically block the receptor from receiving chemical signals that instruct the cell to grow. By interrupting this signaling pathway, the therapy slows or stops the division of cancer cells. This mechanism effectively turns off the “on” switch that the excess HER2 proteins have created.
The second function is to mark the cancer cell for destruction by the body’s immune system. When the antibody binds to the HER2 protein, it signals immune cells, like natural killer (NK) cells, to attack the cancer cell. This process, known as antibody-dependent cell-mediated cytotoxicity (ADCC), leads to the cell’s elimination.
Types of Anti-HER2 Therapies
Anti-HER2 therapies can be categorized into different classes based on their structure and function. The most established class is the monoclonal antibody, with trastuzumab being a primary example. These are “naked” antibodies, composed solely of the antibody molecule that binds to the HER2 receptor. Pertuzumab is another monoclonal antibody that works similarly but binds to a different part of the HER2 protein, preventing it from pairing with other receptors.
A more recent development is the Antibody-Drug Conjugate (ADC), often described as a “smart bomb” approach. An ADC consists of an anti-HER2 monoclonal antibody linked to a potent chemotherapy drug. The antibody component acts as a homing device, delivering the chemotherapy payload directly to HER2-positive cancer cells.
This targeted delivery allows for the use of powerful cytotoxic drugs that would be too toxic to administer systemically. Ado-trastuzumab emtansine (T-DM1) is a well-known ADC where trastuzumab is connected to the chemotherapy drug emtansine. Once T-DM1 binds to a HER2 receptor, it is taken inside the cancer cell, where the chemotherapy agent is released to destroy the cell from within. This approach maximizes the impact on cancer cells while minimizing damage to healthy tissues.
Another category of treatment includes kinase inhibitors, which are small molecule drugs taken orally. Unlike antibodies, these drugs work inside the cell to block the chemical signals that the HER2 protein generates, disrupting the pathways that lead to cell growth. These different types of anti-HER2 therapies provide multiple strategies for targeting HER2-positive cancers, often used in combination or sequence.
Treatment Administration and Side Effects
Anti-HER2 antibody therapies are most commonly administered through an intravenous (IV) infusion in a clinical setting. The frequency of infusions varies depending on the drug and treatment plan but is often scheduled every one to three weeks. Some formulations are available for subcutaneous (under the skin) injection, which can be administered more quickly. The treatment course is determined by the cancer stage and the patient’s overall health.
Patients may experience infusion-related reactions, particularly during the first treatment, including fever, chills, nausea, and headache. These reactions are managed with medications given before the infusion. Other side effects can include diarrhea and a lowered white blood cell count, which increases the risk of infection. Medical teams monitor patients for these effects throughout the treatment period.
A concern with anti-HER2 therapies is the potential for cardiotoxicity, or damage to the heart muscle. The HER2 protein plays a role in the normal function of heart cells, and blocking it can weaken the heart muscle, reducing its ability to pump blood effectively. This may manifest as a decline in the left ventricular ejection fraction (LVEF), a measurement of the heart’s pumping efficiency. In some cases, this can lead to symptoms of congestive heart failure.
Due to this risk, a patient’s heart function is evaluated before starting treatment using an echocardiogram or a multigated acquisition (MUGA) scan. This monitoring continues at regular intervals throughout therapy to detect any changes early. If a decline in heart function is detected, treatment may be paused or stopped to allow the heart to recover. The risk is higher in patients with pre-existing heart conditions or those who have received other cancer treatments known to affect the heart.