Trastuzumab: Transforming the Landscape of Breast Cancer Treatment

Biointron 2024-12-13 Read time: 3 mins

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.

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.

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.

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

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