Trastuzumab, widely known by the brand name Herceptin, is a treatment that transformed the prognosis for certain aggressive cancers. This medication is a recognized and effective therapy for cancers that overexpress a specific protein, primarily breast and gastric cancers. As new cancer treatments like immunotherapy gain prominence, patients often question where established medications like Trastuzumab fit within the evolving landscape of cancer care. The classification of this drug relative to modern immunotherapy requires a nuanced understanding of its mechanism of action.
What is Trastuzumab and What Does it Target?
Trastuzumab is a biologic drug known as a monoclonal antibody (MAb), a laboratory-produced protein designed to mimic the antibodies naturally made by the immune system. It is specifically engineered to target the Human Epidermal growth factor Receptor 2 (HER2) protein. This protein is a transmembrane receptor on the cell surface that plays a role in cell growth, division, and survival.
Cancers classified as “HER2-positive” overexpress this receptor, having many more copies of the protein than normal cells. This high concentration of HER2 drives the uncontrolled growth characterizing these aggressive tumors. Trastuzumab selectively binds to the extracellular domain of the HER2 receptor, essentially marking the malignant cell. The drug is a standard treatment for HER2-positive breast cancer (15% to 20% of all breast cancers) and metastatic gastric or gastroesophageal junction cancers.
Defining Immunotherapy and Targeted Therapy
The medical community divides cancer drug treatments into categories based on their primary method of attack. Targeted therapy involves drugs designed to interfere with specific molecular targets, such as proteins or genes, responsible for the growth and spread of cancer cells. These treatments are highly selective, aiming to block the signals that fuel the tumor while minimizing harm to healthy cells lacking the specific target.
Immunotherapy, in contrast, refers to treatments that harness or enhance the patient’s own immune system to fight the cancer. Instead of directly attacking the cancer cell, these drugs stimulate immune cells, like T-cells or Natural Killer (NK) cells, to recognize and destroy malignant cells. Immunotherapies include checkpoint inhibitors, cancer vaccines, and adoptive cell therapies. The core distinction is whether the drug directly inhibits a cancer-driving pathway or primarily acts by activating the body’s internal defense system.
Trastuzumab’s Dual Mechanism and Classification
Trastuzumab is formally classified as a Targeted Therapy because its primary action is blocking the HER2 receptor. Once the monoclonal antibody binds to the HER2 receptor on the cancer cell surface, it physically prevents the receptor from sending growth signals into the cell’s interior. This action inhibits downstream signaling pathways, such as the MAPK and PI3K/Akt pathways, critical for cell proliferation and survival. By blocking these pathways, Trastuzumab induces cell cycle arrest and leads to the death of the cancer cell.
However, the drug’s mechanism includes a secondary action that incorporates immune system activation, which is why the question of its classification often arises. The antibody structure acts as a flag on the surface of the HER2-positive cancer cell. This flag recruits immune cells, such as Natural Killer (NK) cells, through a process known as Antibody-Dependent Cell-mediated Cytotoxicity (ADCC).
In ADCC, the NK cells recognize the antibody bound to the cancer cell and are triggered to release cytotoxic granules, which destroy the targeted cell. While Trastuzumab’s primary role is receptor blockade, its ability to recruit NK cells makes it a mediator of an immune response against the tumor. Therefore, Trastuzumab is best described as a Targeted Therapy with a significant immune-mediated component, bridging the two classifications without being considered a classic immunotherapy.
Administering Trastuzumab and Common Side Effects
Trastuzumab is typically administered as an intravenous (IV) infusion, where the drug is slowly delivered into a vein, often every two or three weeks. The initial infusion usually takes about 90 minutes, with subsequent doses requiring less time, approximately 30 minutes. For convenience, a subcutaneous (under the skin) injection formulation is also available, which can be given in a fixed dose that takes only a few minutes.
The duration of treatment can range from several months to a full year in the adjuvant setting (after initial surgery or chemotherapy). Trastuzumab is frequently given alongside chemotherapy drugs to enhance its effectiveness against the tumor. While generally well-tolerated, common side effects can include fever, chills, headache, and fatigue, particularly following the first infusion.
The most significant potential adverse effect associated with Trastuzumab is cardiotoxicity, or damage to the heart muscle. This risk exists because the HER2 protein is present on the surface of normal heart muscle cells (cardiomyocytes), and Trastuzumab’s binding can interfere with the signaling pathways necessary for heart function. This side effect often presents as a decline in the heart’s pumping ability, measured by the Left Ventricular Ejection Fraction (LVEF).
Due to this risk, patients require careful cardiac monitoring, including a baseline echocardiogram before starting treatment and regular checks every few months throughout the course of therapy. Fortunately, Trastuzumab-induced cardiotoxicity is often reversible if the drug is temporarily stopped and appropriate cardiac medications are started.