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Quantification of HER family dimers by proximity ligation assay and its clinical evaluation in non–small cell lung cancer patients treated with osimertinib

Lung Cancer May 30, 2021

Liu R, Ota K, Iwama E, et al. - Given that signal transduction by HER (human epidermal growth factor receptor) family proteins relies on their homo- or heterodimerization, however, there is little information on the association between the relative proportions of such dimers of Her1 and sensitivity to EGFR (epidermal growth factor receptor)-TKIs (tyrosine kinase inhibitors), thus, researchers examined the feasibility of evaluating this association with the in situ proximity ligation assay (PLA) technique, which can identify the interaction of two proteins of interest when they are in close proximity. They used non–small cell lung cancer (NSCLC) cell lines and tissue specimens positive for EGFR activating mutations. A reduction in the number of Her1 dimers was brought about by treatment of NSCLC cell lines with EGFR-TKIs, with the impact on homodimers being greater compared with that on heterodimers. In NSCLC patients who received treatment with osimertinib, a poor progression-free survival was observed in relation to a high ratio of Her1 heterodimers to homodimers. According to findings, detection of HER family dimers in NSCLC tissue was enabled by in situ PLA, and quantitative evaluation of Her1 homo- and heterodimers may offer information for prediction of the response to EGFR-TKI treatment in NSCLC cases.

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