BRAF mutation + MET amplification

ICIs could be considered to treat patients whose NSCLCs harbor a METex14 mutation. More biological marker data are needed to identify which patients are most likely to benefit from ICIs.

described a small series of pediatric oligodendroglioma-like tumors with BRAF V600E mutations (3). Interestingly, they exhibited molecular changes usually associated with adult high grade gliomas: chromosome instability, chromosome 7 gains and chromosome 10 loss, but had an indolent natural history.

P2 | "Background: In the ongoing, single-arm, Phase II VISION study (NCT02864992), tepotinib (a highly selective MET inhibitor) showed durable clinical activity in NSCLC patients with MET exon 14 skipping... MET exon 14 skipping can be successfully detected through non-invasive liquid biopsy analysis using next-generation sequencing. The rate of MET exon 14 skipping and the genomic profile and demographics of patients were similar to previously reported data. This abstract and presentation was previously presented at AACR 2020."

NGS offered a less expensive and more reliable model of diagnosis respect to sequential one for patients affected by NSCLC-A.

The study revealed heterogeneous mechanisms of resistance to osimertinib in advanced NSCLC patients and their association with clinical outcomes. Patients who maintained T790M mutation or with EGFR-dependent resistance mechanism had longer clinical outcome benefits.

In the study, cytological specimens and biopsy samples have a very high coincidence rate of gene detection. EGFR, ALK and ROS1 mutations were the main driver mutations in patients with advanced lung adenocarcinoma.We speculate that EGFR and ALK are more prone to concomitant mutations respectively and the treatment of advanced lung adenocarcinoma patients with concomitant mutations deserves further study. The rate of KRAS, NRAS, BRAF, PIK3CA, RET and MET exon14 skipping mutation were low but may had a significant impact on the targeted therapy of patients with advanced lung adenocarcinoma.

Funding: This study was supported by CB16/12/00350 and P118/00226 from ISCIII and Asociación de Mujeres de Apoyo al Cáncer de Mama (AMACMA). AM is recipient of PhD scholarship from Asociación Española Contra el Cáncer (AECC) Valencia Scientific Foundation.

Cetuximab and panitumumab, as the highly effective antibodies targeting epidermal growth factor receptor (EGFR), have clinical activity in the patients with metastatic colorectal cancer (mCRC)...Although the emergence of drug resistance has genetic or epigenetic heterogeneity, most of these molecular changes relating to it are focused on the key signaling pathways, such as the RAS/RAF/mitogen-activated protein kinase or phosphatidylinositol 3-kinase/Akt/mammalian target of the rapamycin pathway. Accordingly, numerous efforts to target these signaling pathways and develop the novel therapeutic regimens have been carried out. Herein, we have reviewed the underlying mechanisms of the resistance to anti-EGFR therapy and the possible implications in clinical practice.

The treatment of lung cancer is increasingly biomarker-driven, as patients are selected for targeted agents based on the identification of genetic alterations amenable to inhibition. Our ability to further improve patient outcomes with this precision medicine approach will require continued efforts to identify, characterize, and target lesions driving lung cancer tumorigenesis and progression.

Routine testing for extended RAS, BRAF, dmmr or high msi, and NTRK fusions is necessary to determine the best sequencing of chemotherapy and biologic agents for patients with mcrc. Although next-generation sequencing and ctdna are increasingly being adopted, other techniques such as immunohistochemistry retain their relevance in detection of her2 amplification, NTRK fusions, and dmmr.

Bypass signaling pathway through c-MET and BRAF are independent mechanisms of resistance to alectinib. Individualized intervention against these resistance pathways could be viable therapeutic options in alectinib-refractory lung adenocarcinoma.

In patients with NSCLC, the cytological material obtained by ultrasound-guided needle aspiration is sufficient for individual and partial molecular analysis in the vast majority of cases. Membrane slides such as cell blocks are valid samples for molecular analysis.