Approved in 1998, trastuzumab (commonly known as Herceptin) marked a transformative milestone in oncology. Designed to target the human epidermal growth factor receptor 2 (HER2), trastuzumab provided a breakthrough for patients with HER2-positive breast cancer, a subset characterized by aggressive tumor growth and poor prognosis.
Targeting the HER2 Receptor
HER2, a transmembrane tyrosine kinase receptor, is overexpressed in approximately 15-20% of breast cancers. Overexpression of HER2 is associated with increased tumor aggressiveness, higher rates of metastasis, and shorter survival. Trastuzumab, a monoclonal antibody, binds specifically to the extracellular domain of the HER2 receptor, inhibiting its downstream signaling pathways.
This mechanism leads to several therapeutic effects:
Suppression of tumor proliferation by blocking HER2-mediated growth signals.
Antibody-dependent cellular cytotoxicity (ADCC), which recruits immune cells to destroy HER2-expressing cancer cells.
Related: Therapeutic Antibodies in Medicine: An Overview
Impact on Breast Cancer Outcomes
Before trastuzumab, HER2-positive breast cancer had limited effective treatment options. Trastuzumab resulted in:
Improved Survival Rates: Clinical trials demonstrated that adding trastuzumab to chemotherapy significantly increased both overall survival (OS) and progression-free survival (PFS) in early-stage and metastatic HER2-positive breast cancer. In some studies, the survival rates nearly doubled when trastuzumab was included.
Reduced Recurrence Rates: Trastuzumab's efficacy in adjuvant (post-surgery) settings reduced the risk of recurrence, giving patients longer disease-free intervals and improving quality of life.
Expanded Applications: The success of trastuzumab in breast cancer led to its use in other HER2-positive cancers, including gastric cancer, further expanding its therapeutic impact.
Continuing Innovations
Despite its success, trastuzumab has limitations. Resistance can develop in some patients, and cardiotoxicity remains a concern, particularly in combination with certain chemotherapeutic agents. To address these challenges, ongoing research focuses on:
Combination Therapies: Pairing trastuzumab with other agents, such as pertuzumab or checkpoint inhibitors, to overcome resistance.
Biosimilars: Developing cost-effective trastuzumab biosimilars to increase accessibility in resource-limited settings.
Next-Generation Antibodies: Innovating antibody-drug conjugates (ADCs) that deliver cytotoxic payloads directly to HER2-positive cells.
Related: The Evolution of Antibody-Drug Conjugates (ADCs) in Cancer Therapy
Trastuzumab’s Legacy
The approval and widespread adoption of trastuzumab heralded a new era in cancer treatment. By significantly improving outcomes for HER2-positive breast cancer patients, it underscored the critical importance of biomarker-driven therapies. The drug remains a cornerstone in oncology, with its principles influencing the development of numerous targeted therapies across various cancers.
Future clinical and experimental studies should investigate how trastuzumab inhibits AKT phosphorylation via HER2/HER3/PI3K/AKT and HER2/SRC/PTEN/AKT signaling pathways in both sensitive and resistant HER2-positive breast tumors. Understanding these mechanisms could uncover the basis of acquired resistance to trastuzumab and support the development of novel combination therapies to enhance its efficacy and overcome resistance. Additionally, research should aim to optimize the trastuzumab-activated ADCC process by modifying its Fc portion or enhancing the activity of immune effector cells involved in ADCC.
Related: How Antibodies are Used in Cancer Immunotherapy
Biointron’s catalog products for in vivo research can be found at Abinvivo, where we have a wide range of Benchmark Positive Antibodies, Isotype Negative Antibodies, Anti-Mouse Antibodies, Bispecific Antibodies, and Antibody-Drug Conjugates, including:
V6 Anti-Human HER2 (Trastuzumab)-B7432
V9 Anti-Human HER2 (Trastuzumab)-BP7432
Anti-Human Her2 (Trastuzumab Deruxtecan)-B23603201
Contact us to find out more at info@biointron.com or +86 400-828-8830 / +1(732)790-8340.
References:
Maadi, H., Soheilifar, M. H., Choi, W., Moshtaghian, A., & Wang, Z. (2021). Trastuzumab Mechanism of Action; 20 Years of Research to Unravel a Dilemma. Cancers, 13(14), 3540. https://doi.org/10.3390/cancers13143540
Antibody specificity refers to an antibody's ability to selectively bind to a unique epitope on a target antigen while avoiding interactions with unrelated antigens. This property arises from the highly specialized antigen-binding site located in the variable region of the antibody, which determines its unique binding characteristics.
Antibody affinity refers to the strength of the binding interaction between a single antigen epitope and the paratope (binding site) of an antibody. This interaction is a fundamental measure of how well an antibody recognizes its specific antigen target.
Recombinant antibodies are produced using genetic engineering techniques, unlike traditional antibody production, where the immune system generates antibodies without direct control over their sequence. By introducing genes encoding antibody fragments into host cells, such as bacteria or mammalian cells, recombinant antibodies can be expressed, purified, and deployed for applications including research, diagnostics, and therapeutics.
Recombinant antibody expression is a biotechnological process that involves engineering and producing antibodies outside their natural context using recombinant DNA technology.
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