Human cells have a protein called human epidermal growth factor receptor 2 (HER2) that helps them grow and divide. In certain cancers, the gene producing this protein is amplified, leading to an overproduction of HER2. This excess protein on the cell surface causes cancer cells to multiply and spread aggressively, and these cancers are identified as HER2-positive.
To combat this, anti-HER2 therapy has been developed. This form of targeted therapy is engineered to seek out and act on HER2-positive cancer cells, distinguishing it from broader treatments like traditional chemotherapy.
How Anti-HER2 Therapy Works
Anti-HER2 therapies function with high specificity, targeting the excess HER2 proteins on the surface of cancer cells. These drugs are designed to recognize and bind directly to the HER2 receptors. This process is often compared to a key fitting into a lock, ensuring the treatment primarily affects cancer cells.
Once attached, the therapy works in two main ways. First, it blocks the HER2 protein from receiving chemical signals that instruct the cell to grow and divide. By interrupting this communication, the treatment slows or stops the proliferation of cancer cells.
The second function is to flag the cancer cell for the body’s defense mechanisms. When the anti-HER2 drug binds to the cell, it acts as a beacon, signaling the immune system to identify and destroy the marked cancer cell. This dual-action approach makes it an effective strategy against HER2-driven cancers.
Types of Anti-HER2 Drugs
Anti-HER2 treatments are categorized into several classes. One primary class is monoclonal antibodies, which are lab-engineered proteins that function like natural antibodies. Drugs such as trastuzumab and pertuzumab fall into this category. Trastuzumab attaches to the HER2 receptor to block growth signals, while pertuzumab binds to a different area of the same receptor, creating a more comprehensive blockade when used in combination.
Another class of these drugs is antibody-drug conjugates (ADCs). These therapies combine a monoclonal antibody with a chemotherapy drug, a design described as a “Trojan horse.” The antibody component attaches to HER2-positive cancer cells and, once absorbed, releases its chemotherapy payload directly inside. This targeted delivery method allows for a powerful attack on the cancer cell while minimizing exposure to healthy tissues. Examples include ado-trastuzumab emtansine (T-DM1) and fam-trastuzumab deruxtecan-nxki.
A third group consists of kinase inhibitors, which are small-molecule drugs administered orally as pills. Unlike antibodies that work on the cell surface, kinase inhibitors function inside the cell. They interfere with the chemical signaling pathways that HER2 activates to promote cell growth, halting the cancer cell’s ability to proliferate. Lapatinib, neratinib, and tucatinib are examples of these inhibitors.
Patient Eligibility and Testing
Anti-HER2 therapy is exclusively for individuals with HER2-positive tumors. This therapy is most frequently associated with breast cancer, where about 15-20% of tumors are HER2-positive. It is also used for certain types of gastric, gastroesophageal junction, salivary gland, and colorectal cancers that overexpress the HER2 protein.
A patient’s HER2 status is determined from a tumor tissue sample using two main laboratory tests. The first is Immunohistochemistry (IHC), a process that uses stains to measure the quantity of HER2 protein receptors on the surface of the cancer cells.
The second test is Fluorescence In Situ Hybridization (FISH), which counts the number of HER2 genes within the cancer cells. An excessive number of genes corresponds to the overproduction of the protein. The outcomes of the IHC and FISH tests are used together to determine if a cancer is HER2-positive and guide the clinical decision to begin anti-HER2 therapy.
Potential Side Effects of Treatment
While anti-HER2 therapies target cancer cells specifically, they can still cause side effects. A significant concern with some of these drugs, particularly monoclonal antibodies like trastuzumab, is their potential impact on the heart. This can manifest as a weakening of the heart muscle, which may decrease its ability to pump blood effectively and, in some cases, lead to congestive heart failure. For this reason, a patient’s cardiac function is carefully evaluated with tests like an echocardiogram before treatment begins and is monitored regularly throughout the course of therapy.
Other more common side effects are generally less severe and can often be managed with supportive care. Patients may experience diarrhea, particularly with kinase inhibitors. General fatigue, mild nausea, and skin rashes are also frequently reported across the different classes of anti-HER2 drugs.
It is important for patients to maintain open communication with their healthcare team about any symptoms they experience. Promptly reporting side effects allows medical professionals to provide interventions that can alleviate discomfort and manage potential complications. This collaborative approach helps ensure the treatment can continue safely and effectively.