Pertuzumab and trastuzumab are targeted therapies used in the treatment of certain cancers that exhibit an overexpression of a specific protein. These medications are designed to specifically interfere with the growth signals of cancer cells, rather than broadly affecting all rapidly dividing cells like traditional chemotherapy. By focusing on a particular molecular pathway, these therapies aim to provide a more precise approach to cancer treatment. They represent significant advancements in managing HER2-positive malignancies.
The Role of HER2 in Cancer
HER2, or Human Epidermal growth factor Receptor 2, is a protein on cell surfaces that regulates cell growth, division, and repair. It is a member of the human epidermal growth factor receptor (HER/EGFR/ERBB) family. Normally, HER2 controls how quickly cells grow and divide.
When HER2 genes make too many copies, it leads to an excess of HER2 proteins on the cell surface, known as overexpression or amplification. This disrupts normal cell growth regulation, causing cells to multiply too quickly and uncontrollably. HER2-positive cancers, accounting for about 15% to 20% of breast cancers, tend to be more aggressive, growing faster and having a higher likelihood of spreading and recurring. Despite their aggressive nature, these cancers are often more responsive to specific targeted treatments because HER2 provides a direct target for therapy.
Targeted Action of Pertuzumab and Trastuzumab
Pertuzumab and trastuzumab are humanized monoclonal antibodies, laboratory-made proteins designed to specifically target substances. These antibodies bind to the HER2 protein on cancer cells at different locations, leading to complementary mechanisms of action. Trastuzumab primarily binds to domain IV of the HER2 extracellular domain, inhibiting cell signaling pathways that promote cell growth and survival. It can block HER2 from sending growth signals and also signal the immune system to destroy cancer cells.
Pertuzumab targets a different region: subdomain II of the HER2 extracellular domain. This region is involved in HER2’s pairing with other HER family receptors, a process called dimerization. Pertuzumab prevents HER2 from forming these pairs, particularly with HER3, an activator of growth signals in cancer cells. By blocking this dimerization, pertuzumab inhibits signaling pathways that drive cell proliferation and survival.
When used together, pertuzumab and trastuzumab provide a more comprehensive blockade of the HER2 signaling pathway than either drug alone. Trastuzumab interferes with HER2 signaling and can induce an immune response, while pertuzumab prevents the formation of HER2 heterodimers important for cancer cell growth. This dual blockade offers enhanced anti-tumor activity by attacking the HER2 pathway from multiple angles, leading to improved outcomes for patients.
Undergoing Treatment with Pertuzumab and Trastuzumab
The combination therapy of pertuzumab and trastuzumab is used for HER2-positive breast cancer, including early-stage, locally advanced, inflammatory, and metastatic forms. It is also indicated for HER2-positive gastric cancer. These medications are typically administered intravenously. The treatment regimen often involves combining these targeted therapies with chemotherapy, particularly a taxane like docetaxel.
Patients usually receive pertuzumab and trastuzumab infusions every three weeks. The duration of treatment varies depending on the cancer stage and individual patient needs. Common side effects include diarrhea, hair loss, nausea, and fatigue. Diarrhea, in particular, can be more frequent with pertuzumab.
Monitoring for serious side effects is important. Cardiac dysfunction, specifically a decrease in left ventricular ejection fraction, is a known risk with HER2-targeted therapies, so heart function is regularly assessed before and during treatment. Infusion reactions, which can occur during or shortly after administration, are also monitored and managed by healthcare providers. Treatment plans are individualized, considering the patient’s cancer characteristics and overall health, to optimize effectiveness and manage side effects.