What is HER2 and EGF receptor antagonist?
a. Lapatinib is an orally active chemotherapeutic agent used for treatment of solid cancers. It is considered to be a dual inhibitor of tyrosine kinase enzyme domains. It blocks HER2 and EGFR.
b. Main advantage of the drug is its oral administration. The drug has recently been approved by FDA in combination with capecitabine for transtuzumab resistant patients of breast cancer over expressing HER2/neu receptors (CMDT’2010, pp-668). Bevacizumab was also approved in early 2008 for breast cancer and is VEGF antagonist.
c. The drug is particularly useful in HER2 positive cancers when other treatments have failed. Recall, trastuzumab is HER2 antagonist and is used in advanced or metastatic type of breast cancer.
d. Studies are underway to know if the drug could be used as first line therapy also in breast cancer. The drug is very well tolerated (BG Katzung’ 10th Edition, 2010).
e. Geftinib is an EGFR domain inhibitor of tyrosine kinase and is used to treat those patients of non-small cell lung cancer who have not responded to other drugs. the drug comes as an oral tablet and can be taken with or without food. The drug is well tolerated. Acne can occur.
f. Erlotinib is also an EGFR domain inhibitor of tyrosine kinase enzyme. it is used for non small cell cancer and cancer of pancreas with cisplatin. The drug has been shown to have survival benefit in clinical trials as opposed to geftinib. Rashes are major side effects.
g. EGFR is over expressed in the cells of certain types of human carcinomas - for example in lung and breast cancers. This leads to inappropriate activation of the anti-apoptotic RAS signalling cascade, eventually leading to uncontrolled cell proliferation.
h. Research on gefitinib-sensitive non-small cell lung cancers has shown that a mutation in the EGFR tyrosine kinase domain is responsible for activating anti-apoptotic pathways. These mutations tend to confer increased sensitivity to tyrosine kinase inhibitors such as gefitinib and erlotinib. Of the types of non-small cell lung cancer histologies, adenocarcinoma is the type that most often harbors these mutations.
i. Imatinib is the first of the clinically used tyrosine kinase inhibitors. The drug is well absorbed orally and undergoes extensive CYP dependent metabolism. It can also be an inhibitor of drug metabolism. Major route of elimination is bile. It is used for CML, GIST and several other tumors. Side effects are non specific.
(Mnemonics: Lapatinib is used in breast lump (breast cancer).We all have two breast so act on both the receptor)