Targeting the HER2 oncogene represents one of the greatest advances in the treatment of breast cancer. HER2 is one member of the ERBB-receptor family, which includes EGFR (HER1), HER3 and HER4. In the presence or absence of underling genomic aberrations such as mutations or amplification events, intricate interactions between these proteins on the cell membrane lead to downstream signaling that encourages cancer growth and proliferation. In this Review, we contextualize efforts to pharmacologically target the ErbB receptor family beyond HER2, with a focus on EGFR and HER3. Preclinical and clinical efforts are synthesized. We discuss successes and failures of this approach to date, summarize lessons learned, and propose a way forward that invokes new therapeutic modalities such as antibody drug conjugates (ADCs), combination strategies, and patient selection through rational biomarkers.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10478787 | PMC |
| http://dx.doi.org/10.1016/j.ctrv.2022.102436 | DOI Listing |
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Article Synopsis
- The study examines the effects of a combination therapy (apatinib and trastuzumab-based chemotherapy) on patients with primary trastuzumab resistance (PTR) in HER2-positive breast cancer.
- A total of 20 PTR patients were treated, showing a clinical benefit rate of 55%, though no complete responses were observed, and median progression-free survival was 5.7 months.
- While the treatment had manageable side effects, further research is recommended to better identify which PTR patients could potentially benefit from this therapy.
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