STK11 deletion

CONCLUSION STK11 and KEAP1 deletion may be linked to generally worse outcomes to ICI in KRASMUT NSCLC. Future analyses will explore this question in an independent cohort and assess the impact of these deletions on protein expression by immunohistochemistry.

This study revealed the mechanism of STK11 mutation regulating NK cytotoxicity and promoting tumor development, providing scientific basis for the exploration of STK11-related LUAD therapeutic targets and theoretical reference for developing new NK cell-based immunotherapy.

STK11 deletion is associated with low response rate and short progression-free survival among KRAS mutant NSCLCs. Future analyses will incorporate additional cases to increase sample size and immunopathologic findings to assess impact of mono and bi-allelic deletion on protein expression.

We successfully generated a CT26-STK11KO cell line which was valuable for evaluation of PD-1 blocker and MEK inhibitor in STK11/LTB1 deficient tumor, in which Trametinib could rescue the efficacy of PD-1 treatment in CT26-STK11KO tumor via inhibiting G-MDSC. Taken together, our data suggest that altered immune cell infiltration, particularly increased G-MDSCs, in tumor microenvironment might be the reason for poor PD-1 blocker efficacy in CT26-STK11KO tumor.

Additional biomarkers beyond PD-L1 that have been shown to have predictive capacity include tumor mutational burden, microsatellite instability, lung immune prognostic index, gut microbiome, and certain alterations in genes (eg, STK11 deletion, LKB1 kinase mutation, MDM2/4 amplification) that confer immunoresistance. The biomarkers reviewed in this article could help us better select the appropriate immunotherapy treatment for patients with NSCLC.

This study highlights the genomic heterogeneity in CTCs seen in MBC and the potential of monitoring gene specific changes to identify actionable targets in order to inform treatment decisions. The work requires further evaluation and validation but it may offer a new approach to managing treatment decisions in MBC for those patients with detectable CTCs.

Palbociclib could reverse afatinib, docetaxel, & radiation resistance...CDK7/8/9/12/13 are involved in RNA polymerase II function with RNA elongation pause/release, transcription & onco-histones control, and SWI/SNF superfamily with epigenetic modifications. HNSCC cell lines(SCC4, SCC9, SCC15, SCC25, FaDu, KB, Cal27, SAS, and TW2.6, betel-nuts related) were tested in (1)in vitro sensitivity to CDK inhibitors; (2)synergistic effect of AZD4573(CDK9 inhibitor) with other therapies by MTT assay, colony formation, flow cytometry, & western blotting; (3) NGS studies to elucidate molecular mechanisms. Palbociclib response correlated to CCND1 gain & CDKN2A deletion; but FaDu had poor response with both and TW2.6 had good response without both... CCND1 gain & CDKN2A deletion could not fully predict CDK4/6 inhibitor response. TW2.6 is responsive to CDK4/6 inhibitors(palbociclib>ribociclib>abemaciclib). FAT1 loss, CCND3 amplification, PI3K/AKT/mTOR derangements, & FGFR amplification might imply CDK4/6 inhibitor resistance.

LKB1 loss was associated with increased mitochondrial ROS and stabilization of HIF1a, and downregulation of LKB1 and increased levels of HIF1a were observed in human blast phase MPN specimens. Of note, we observed strong concordance of pathways that were enriched in murine MPN cells with LKB1 loss with those enriched in blast phase MPN patient specimens, supporting the conclusion that STK11 is a tumor suppressor in the MPNs.