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Development Of Drugs With High Potency And Inhibitory Activity

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Summary of research plan
Development of drugs with high potency and inhibitory activity against specific activating mutation, while showing significantly less activity against wild type mutations, made testing specific sensitizing mutation necessary. (1) (EGFR) T790M mutation a successful example of a biomarker for non-small cell lung cancer (NSCLC) treatment with Osimertinib that gained a wide acceptance in clinical practice in Europe and US (), One question that needs to be asked, however, is whether testing for similar mutations in different cancer will be of clinical value. an unknown subpopulation of patients with CRC will have an activating EGFR mutation, such as L858R, which is thought to activate the receptor constitutively, regardless of ligand status promoting cellular proliferation and growth. in patients with colorectal cancer, Targeting activated EGFR, hypothetically, will lead to growth inhibition of cancer cell dependent on the oncogenic drive of sensitising EGFR mutation. This project aims to investigate the role of EGFR (L858R/+/+) as a biomarker for AZD 9291 (Osimertinib) treatment, using SW48 cell line with a wild type mutation of EGFR and Heterozygous knockin of EGFR activating mutation (L858R/+/+), to investigate the mechanism of resistances if cells developed resistance and to test the overlap between Osimertinib and AZD5363, palbocidib and selumetinib.
This work should improve treatment outcome for patients with CRC with EGFR sensitising mutation

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