EGFR-mutant lung cancers can acquire RET fusion-mediated bypass resistance to osimertinib. Rotow and colleagues present the largest series of patients with these cancers who were prospectively treated in a multicenter cohort with the combination of EGFR and RET kinase inhibitor therapy (osimertinib and selpercatinib). The majority of patients benefitted from treatment with a response rate of 50%, a disease control rate of 83%, and a median treatment of duration 7.9 months, highlighting the potential use of the combination in clinic. On-target (second site EGFR or RET kinase domain mutations), off-target (ALK fusion, KRAS/BRAF mutation), and polyclonal resistance were observed. The authors propose that further treatment relapse can be mediated by competing clones harboring steric hindrance to EGFR/RET kinase engagement or non-EGFR/RET-mediated MAPK pathway reactivation.

Low overall survival (OS) rates in post-treatment glioblastoma (GBM) patients highlight a need for new treatment options. Enrichment of immunosuppressive, extracellular-facing phosphatidylserine (PS) in GBM makes...

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