HER2 tyrosine kinase inhibitors
Oral small molecules that block the HER2 kinase from inside the cell; used in HER2-positive breast cancer, often after or with trastuzumab.
What they are
Lapatinib (HER2 and EGFR), neratinib (irreversible HER2 and EGFR) and tucatinib (HER2-selective) inhibit the intracellular kinase domain of HER2, while antibodies such as trastuzumab bind its outside. They are combined with capecitabine, trastuzumab or endocrine therapy in HER2-positive breast cancer.
Mechanism of action
HER2 (ERBB2) is a member of the EGFR family; when it is overexpressed it pairs with other family members and its kinase drives proliferation. These drugs occupy the ATP site of the HER2 kinase and switch the signal off. Blocking the receptor from inside complements antibodies that block it from outside.
Target: HER2 (ERBB2) tyrosine kinase, with EGFR for lapatinib and neratinib
Drugs in this class
- LapatinibAn oral dual HER2 and EGFR kinase inhibitor for HER2-positive breast cancer, with capecitabine or letrozole. Boxed…HER2 (ERBB2) and EGFR tyrosine kinases
- TucatinibA HER2-selective oral kinase inhibitor, with trastuzumab and capecitabine, for HER2-positive breast cancer, including…HER2 (ERBB2) tyrosine kinase
Others in the class
- neratinib
Test yourself
Think of the answer, then tap the question to see it.
How do HER2 kinase inhibitors differ from trastuzumab in where they act?
They block the kinase inside the cell; trastuzumab binds the outside of the receptor.
Which HER2 inhibitor also inhibits EGFR reversibly?
Lapatinib.
Why does tucatinib cause less rash than lapatinib?
It is HER2-selective and barely inhibits EGFR, whose blockade causes the skin toxicity.
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026); Tucatinib - NCI (National Cancer Institute, 2024).
Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake
Representative model, for educational purposes only.