T790M
T790M, also known as Thr790Met, is a gatekeeper mutation of the epidermal growth factor receptor (EGFR). The mutation substitutes a threonine (T) with a methionine (M) at position 790 of exon 20,[1] affecting the ATP binding pocket of the EGFR kinase domain. Threonine is a small polar amino acid; methionine is a larger nonpolar amino acid.
Clinical
Over 50% of acquired resistance to EGFR tyrosine kinase inhibitors (TKI) is caused by a mutation in the ATP binding pocket of the EGFR kinase domain involving substitution of a small polar threonine residue with a large nonpolar methionine residue, T790M.[2][3]
In November 2015, the US FDA granted accelerated approval to osimertinib (Tagrisso) for the treatment of patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC), as detected by an FDA-approved test, which progressed on or after EGFR TKI therapy.[4][5]
References
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- ↑ U.S. Food and Drug Administration. Hematology/Oncology (Cancer) Approvals & Safety Notifications. [1]
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