What is Human Epidermal Growth Factor Receptor 2 (HER2)?
Human Epidermal Growth Factor Receptor 2, commonly known as
HER2, is a protein that resides on the surface of cells. It is involved in normal cell growth and differentiation. However, when HER2 is overexpressed or amplified, it can lead to uncontrolled cell growth and the development of cancer. This condition is particularly noted in
breast cancer but can also be found in other cancers such as gastric, ovarian, and lung cancers.
How Does HER2 Contribute to Cancer?
HER2 is part of the
ErbB family of receptors. These receptors are tyrosine kinases that play a crucial role in the regulation of cell growth and survival. When HER2 is overexpressed, it leads to the persistent activation of these signaling pathways, causing excessive cell proliferation and survival, which eventually contributes to
tumorigenesis. HER2-positive cancers are often more aggressive and have a higher likelihood of recurrence compared to HER2-negative cancers.
How is HER2 Status Determined?
Determining the HER2 status of a tumor is crucial for diagnosis and treatment planning. Two primary tests are used to measure HER2 status:
Based on these tests, tumors can be classified as HER2-positive, HER2-negative, or equivocal. Additional testing may be required for equivocal results.
Trastuzumab (Herceptin): A monoclonal antibody that binds to the HER2 protein and inhibits its function.
Pertuzumab (Perjeta): Another monoclonal antibody that works synergistically with trastuzumab to block HER2 signaling pathways.
Ado-trastuzumab emtansine (Kadcyla): A conjugate of trastuzumab and a cytotoxic agent, designed to deliver chemotherapy directly to HER2-positive cells.
Lapatinib (Tykerb): A small molecule tyrosine kinase inhibitor that targets both HER2 and EGFR pathways.
These treatments have significantly improved the prognosis for patients with HER2-positive cancers, providing better survival rates and quality of life.
Drug Resistance: Over time, cancer cells can develop resistance to HER2-targeted therapies, necessitating the need for alternative treatments.
Toxicity: Some patients may experience severe side effects from these treatments, which can limit their use.
Heterogeneity: Tumors can be heterogeneous, meaning that not all cells within the tumor express HER2 uniformly, complicating treatment strategies.
Ongoing research is focused on overcoming these challenges through the development of new drugs, combination therapies, and personalized medicine approaches.
Bispecific Antibodies: These antibodies are designed to target two different antigens simultaneously, potentially increasing efficacy.
Antibody-Drug Conjugates (ADCs): Newer ADCs are being developed to deliver more potent cytotoxic agents to HER2-positive cells.
Immune Checkpoint Inhibitors: Combining HER2-targeted therapies with immune checkpoint inhibitors may enhance the immune response against cancer cells.
Furthermore,
liquid biopsies and other advanced diagnostic tools are being explored to better monitor treatment response and detect resistance early.
