HER2 targeted therapy is a specialized approach in cancer treatment, focusing on specific molecular characteristics of cancer cells. It aims to precisely interrupt pathways that drive cancer growth. Unlike traditional, broad-acting therapies, this strategy offers a focused attack on certain cancers, improving treatment effectiveness for those who qualify.
The Role of HER2 in Cancer
The HER2 gene provides instructions for making the HER2 protein, a receptor located on the surface of various cells. This protein plays a role in cell growth, division, and repair by receiving signals from outside the cell. In some cancers, cells produce an abnormally high number of these HER2 receptors, a condition known as “HER2-positive.” This overexpression leads to uncontrolled cell growth and division, making the cancer more aggressive.
Cancers most commonly associated with HER2 positivity include certain types of breast cancer and gastric (stomach) cancer. Identifying HER2 status is a routine diagnostic step, determining if a patient is a candidate for targeted therapy. Tests such as Immunohistochemistry (IHC) measure the amount of HER2 protein on the cell surface. Fluorescence In Situ Hybridization (FISH) can also be used to count the number of HER2 gene copies within the cancer cells.
Mechanism of HER2 Targeted Therapy
HER2 targeted therapy operates on a principle of selective engagement, differing from conventional chemotherapy that affects both healthy and cancerous cells. These specialized drugs identify and attach to the HER2 protein found in abundance on HER2-positive cancer cells. Once bound, the drugs interfere with the signaling pathways that promote cell growth and division, aiming to halt or slow cancer progression.
This precision minimizes damage to healthy cells, leading to different side effect profiles compared to traditional systemic chemotherapy.
Classes of HER2 Targeted Drugs
Monoclonal Antibodies
Monoclonal antibodies are laboratory-produced proteins designed to mimic the body’s immune system. These therapies work by attaching to the HER2 receptors located on the exterior surface of cancer cells. This binding action directly blocks the growth signals that the HER2 receptor would otherwise transmit into the cell. Some monoclonal antibodies can also mark the cancer cells, making them more visible targets for destruction by the body’s own immune system. Examples of these drugs include trastuzumab and pertuzumab, which are commonly used in HER2-positive breast and gastric cancers.
Antibody-Drug Conjugates (ADCs)
Antibody-drug conjugates (ADCs) are a class of HER2-targeted therapy, often described as a “Trojan horse” approach. An ADC combines a monoclonal antibody, which targets the HER2 protein, with a potent chemotherapy drug. The antibody delivers the chemotherapy agent directly to HER2-positive cancer cells. This precise delivery minimizes systemic exposure of healthy tissues to chemotherapy, reducing widespread side effects. Examples include ado-trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan.
Kinase Inhibitors
Kinase inhibitors are small-molecule drugs, often administered as oral pills, that function differently from antibodies. These drugs are designed to penetrate the cell membrane and act from within the cancer cell. They specifically block the activity of tyrosine kinases, enzymes that are part of the HER2 signaling pathway inside the cell. By inhibiting these internal signals, kinase inhibitors disrupt the cascade of events that drive cancer cell growth and survival. Examples of these oral medications include lapatinib, neratinib, and tucatinib, offering an alternative mechanism to block HER2-driven proliferation.
Treatment Regimens and Side Effects
The administration of HER2 targeted therapies varies by drug class. Monoclonal antibodies and antibody-drug conjugates are administered intravenously (IV) in a clinic or hospital. Kinase inhibitors are taken as oral medications, offering a convenient administration route. These therapies are used in combination with each other or alongside traditional chemotherapy to enhance effectiveness.
Patients undergoing HER2 targeted therapy may experience side effects that differ from conventional chemotherapy. Common side effects include diarrhea, fatigue, and skin rash, which are managed with supportive care and medication.
Cardiotoxicity, affecting heart function, is a side effect requiring close monitoring. HER2 receptors are present on heart cells, and some HER2-targeted drugs can impact the heart’s ability to pump blood. To mitigate this risk, heart health is assessed before and throughout treatment, often involving echocardiograms to monitor cardiac function.
Monitoring Efficacy and Addressing Resistance
Monitoring the effectiveness of HER2 targeted therapy is a regular part of cancer management. Doctors use various methods to assess cancer response. Imaging scans, such as CT (computed tomography) or PET (positron emission tomography) scans, visualize changes in tumor size or activity. Blood tests for specific tumor markers can also provide insights into treatment response.
Despite initial success, some cancers develop acquired resistance to a particular HER2-targeted drug. This means cancer cells adapt and find new ways to grow, making the initial therapy less effective. The development of resistance is a recognized challenge. The availability of multiple classes and generations of HER2 drugs offers subsequent treatment options if resistance occurs.