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Gefitinib has been shown to be an effective tyrosine kinase inhibitor in a fraction (~$10$%) of non-small cell lung cancer patients.

These patients are characterized as having a mutation (usually a deletion or missense) in the EGFR gene affecting the ATP-binding site.

I have two questions:

-- How does gefitinib impede the proliferation and apoptosis pathway? Does it in effect "ace out" the binding of EGF? If this is correct, how does it accomplish that? If not, I would appreciate a brief explanation as to what the successful mechanism is.

-- It seems that (similar to imatinib, another tyrosine kinase used to treat CML) successfully treated patients tend to relapse after a period of time. Why is this?

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    $\begingroup$ I suspect this question would fit better on the Biology or Medical Sciences SE pages. $\endgroup$ – Tyberius Mar 2 at 18:15
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How does gefitinib impede the proliferation and apoptosis pathway? Does it in effect "ace out" the binding of EGF? If this is correct, how does it accomplish that? If not, I would appreciate a brief explanation as to what the successful mechanism is.

enter image description here No, EGF binds on the extracellular side (to the ectodomain), and gefitinib binds on the intracellular side (to the tyrosine kinase, purple in the figure). The inhibitor interferes with ATP binding (see below, middle panel - the part boxed in green has structural similarities to adenine in ATP). The ATP would otherwise phosphorylate the tyrosines of other signalling proteins. So even if EGF binds to the ectodomain, there is no downstream effect because the tyrosin kinase domain is inhibited.

enter image description here

Source of images: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523254/

I recommend section 3.2 to learn about how various inhibitors work.

It seems that (similar to imatinib, another tyrosine kinase used to treat CML) successfully treated patients tend to relapse after a period of time. Why is this?

Additional mutations might directly prevent the drug from binding, or change signalling pathways in a different fashion to render the drug inefficient.

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