Combining tissue and circulating tumor DNA increases the detection rate of a CTNNB1 mutation in hepatocellular carcinoma.

Background And Aims: Studies suggest that mutations in the CTNNB1 gene are predictive of response to immunotherapy, an emerging therapy for advanced hepatocellular carcinoma (HCC). Analysis of circulating tumor DNA (ctDNA) offers the possibility of serial non-invasive mutational profiling of tumors. Combining tumor tissue and ctDNA analysis may increase the detection rate of mutations.

Epithelial-to-mesenchymal transition is a resistance mechanism to sequential MET-TKI treatment of -amplified EGFR-TKI resistant non-small cell lung cancer cells.

Background: Tyrosine kinase inhibitor (TKI) resistance is a major obstacle in treatment of non-small cell lung cancer (NSCLC). amplification drives resistance to EGFR-TKIs in 5-20% of initially sensitive.

Egfr: mutated NSCLC patients, and combined treatment with EGFR-TKIs and MET-TKIs can overcome this resistance.

Circulating miR-30b and miR-30c predict erlotinib response in EGFR-mutated non-small cell lung cancer patients.

Objectives: MiR-30b, miR-30c, miR-221 and miR-222 are known to induce gefitinib resistance in lung cancer cell lines with activation of mutations in the epidermal growth factor receptor (EGFR). However, the role of these four microRNAs in tyrosine kinase inhibitor (TKI)-resistance in non-small cell lung cancer (NSCLC) patients is unknown. Thus, the aim of this study was to investigate the predictive value of miR-30b, miR-30c, miR-221 and miR-222 in plasma from EGFR-mutated lung cancer patients receiving erlotinib.

Up-Regulated FGFR1 Expression as a Mediator of Intrinsic TKI Resistance in EGFR-Mutated NSCLC.

Non-small cell lung carcinoma patients with epidermal growth factor receptor (EGFR) mutations are offered EGFR tyrosine kinase inhibitors (TKI) as first line treatment, but 20-40% of these patients do not respond. High expression of alternative receptor tyrosine kinases, such as Fibroblast growth factor receptor 1 (FGFR1), potentially mediates intrinsic EGFR TKI resistance. To study this in molecular detail, we used CRISPR-dCas9 Synergistic Activation Mediator (SAM) for up-regulation of FGFR1 in physiological relevant levels in the EGFR mutated NSCLC cell lines HCC827 and PC9 thereby generating HCC827 and PC9.