Relevance of detection the mechanisms of resistance to ALK TKIs in ALK positive NSCLC

Helden, Guusje van (2021) Relevance of detection the mechanisms of resistance to ALK TKIs in ALK positive NSCLC. Bachelor's Thesis, Biology.

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Abstract

ALK positive NSCLC patients are treated with tyrosine kinase inhibitors (TKIs), however most patients become resistant and develop a relapse. On-target and off-target mechanisms contribute to resistance in ALK positive NSCLC. For on-target mechanisms, L1196M is thought to be the main driver of crizotinib resistance, while G1202R is thought to be the main driver of alectinib resistance. It remains unclear whether ALK resistance mutations, specifically L1196M, can be detected in treatment naive tumors. However, monitoring concentration of both L1196M and G1202R, by taking liquid biopsies predicts a patients’ clinical course and may improve treatment options. ddPCR seems to be the most effective tool to detect ALK TKI resistance mutations in liquid biopsies, but when a larger gene panel must be investigated, NGS seems to be a better tool. When no on-target resistance mechanisms can be found, it should be considered to analyse any off-target resistance mechanisms. Activation of the by-pass signaling pathway EGFR in ALK positive patients, contributes to resistance and may even be detected before start of treatment. Better treatment can be given when the mechanism of resistance in an ALK positive NSCLC patient is well understood, which therefore improves a patients’ clinical outcome.

Item Type:	Thesis (Bachelor's Thesis)
Supervisor name:	Berg, J.H.M. van den
Degree programme:	Biology
Thesis type:	Bachelor's Thesis
Language:	English
Date Deposited:	21 Jun 2021 16:04
Last Modified:	22 Jun 2021 14:35
URI:	https://fse.studenttheses.ub.rug.nl/id/eprint/24642

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