MET (MET proto-oncogene, receptor tyrosine kinase)

Crizotinib demonstrated clinical activity across tumors with METamp and METex14.Subprotocol C1, but not C2, met its primary endpoint. In METex14 disease, a read count cutoff >50,000 may help distinguish true pathogenic variants from low-level splice transcripts and enable more accurate classification.

AFP (Alpha-fetoprotein) and GFAP (Glial Fibrillary Acidic Protein) emerged as potential biomarkers from the primary lesion for BM onset, while network analysis identified MET (MET Proto-Oncogene, Receptor Tyrosine Kinase), GDF15 (Growth Differentiation Factor 15), and S100A9 (S100 Calcium Binding Protein A9) as candidate mediators of tumour-brain crosstalk. These results offer new insights into EOC brain tropism, highlighting potential targets for therapeutic intervention and personalized patient management in the precision oncology era.

Moreover, they demonstrated high accuracy in identifying cases lacking alterations. Our results highlight the potential of deep-learning tools for the detection of NSCLC biomarkers and specifically the identification of tumors without EGFR or ALK driver alterations, supporting more informed clinical decision-making.

The clinical course of this patient was interesting clinical information in terms of providing insight into the morphology, imaging findings, and origin of MET exon 14 skipping gene-positive adenocarcinoma.

The targets evaluated have potential drugs currently under trial phase. This may help to define the subgroup for use of targeted therapy in NSCLC-SCC and in designing new treatment protocols.

Importantly, we demonstrated dual-targeting by oAds encoding the two bispecific TCEs or the Db-TriTE with the latter featuring superior genomic stability and the overall highest efficacy. Taken together, we report novel bi- and trispecific TCEs and proof of principle for their application as dual-targeted viro-antibody therapy.

After resolution with corticosteroids, treatment was switched to afatinib. This study highlights the heterogeneous approaches to OILI and the potential feasibility of rechallenge in selected patients. Given the expanding osimertinib use for early and advanced stage NSCLC, further research is warranted to refine treatment decisions and optimize patient safety.

The savolitinib-osimertinib combination improved PFS versus chemotherapy in patients with EGFR mutation-positive, MET-amplified NSCLC that had progressed on EGFR TKI therapy, while maintaining a favourable tolerability profile. This regimen offers a potential oral treatment option for this biomarker-selected population.

Multigene testing is underutilized in this population. While many targeted therapies carry a high risk of pneumonitis, sotorasib appeared relatively safe. Despite the risks, identifying and treating actionable oncogenic drivers may improve survival.

Prevalence of secondary RET mutations after SRIs was low, underscoring greater role for off-target resistance. Recurrent acquired alterations involving tumor suppressor genes or upstream regulators of MAPK and PI3K pathways were identified, most commonly MET amplification. Continued efforts to characterize SRI resistance biology are critical to guide development of novel therapeutic strategies.

Our studies have demonstrated that TPD354 exhibits metabolic stability in liver microsomes and is characterized by high plasma protein binding, with a half-life of approximately 16 h in rats. These findings suggest that TPD354 is a promising PROTAC drug candidate, with strong potential for the treatment of c-Met targeted cancer.

Treatment-related adverse events of grade 3 or higher occurred in 2 patients (8.7%) in cohort 1 and 12 patients (57.1%) in cohort 2. Osimertinib plus savolitinib showed promising antitumor activity and manageable safety.