HER2 tyrosine kinase inhibitors
Small pills that block HER2 from inside the cell, complementing antibody drugs; tucatinib is notable for working against brain metastases.
Overview
Lapatinib (2007), neratinib (2017) and tucatinib (2020) are oral kinase inhibitors of HER2, with lapatinib and neratinib also hitting EGFR. Tucatinib, more selective and so less prone to diarrhoea and rash, improved survival with trastuzumab and capecitabine in the HER2CLIMB trial including patients with brain metastases, and gained a colorectal cancer indication in 2023. Neratinib is used as extended adjuvant therapy after trastuzumab.
How it works
ATP-competitive inhibitors bind the intracellular kinase domain of HER2, blocking downstream signalling even when antibodies cannot reach the tumour, such as behind the blood-brain barrier.
- Oral
- Activity against brain metastases
- Combine with antibodies and chemotherapy
- Diarrhoea, especially with neratinib and lapatinib
- Resistance through HER2 mutations and pathway bypass
Latest papers
topQuery for this technology: (TITLE:"HER2 tyrosine kinase inhibitors" OR ABSTRACT:"HER2 tyrosine kinase inhibitors") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about HER2 tyrosine kinase inhibitors, not a curated reading list.
Similar pages
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