Lapatinib, a Dual-Targeted Small Molecule Inhibitor of EGFR and HER2, in HER2-Amplified Breast Cancer: From Bench to Bedside
Bibliographic record
Abstract
The HER-2/neu gene product is a 185 kDa Type I receptor tyrosine kinase which consists of an extracellular domain, transmembrane domain, kinase domain, and cytoplasmic tail. The initial discovery that amplification and subsequent overexpression of the HER-2/neu oncogene plays a pivotal role in the pathogenesis of 20%–25% of breast cancers has since led to significant clinical advances in the management of this subtype of breast cancer. The first approved HER2-targeted therapy, trastuzumab, is a humanized monoclonal antibody against the extracellular domain of HER2 and has demonstrated survival benefits in both the metastatic and adjuvant settings. Lapatinib, a small molecule tyrosine kinase inhibitor of both the epidermal growth factor receptor (EGFR) and HER2 is now also approved for advanced HER2-amplified breast cancer and is currently being evaluated in the adjuvant setting. Importantly, lapatinib has been shown to have activity in women with HER2-amplified breast cancer that is refractory to trastuzumab. In addition, it has been shown to extend survival in the front-line setting in combination with letrozole for estrogen receptor (ER) positive, HER2-positive breast cancer. Here we will review the biologic rationale and pre-clinical data that drove its initial clinical development as well as current clinical data and ongoing studies.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".