Spatial profiling of METex14-altered NSCLC under tepotinib treatment: Shifting the immunosuppressive landscape.

MET inhibitors have demonstrated efficacy in treating patients with non-small cell lung cancer (NSCLC) harboring METex14 skipping alterations. Advancements in spatial profiling technologies have unveiled the complex dynamics of the tumor microenvironment (TME), a crucial factor in cancer progression and therapeutic response. This study uses spatial profiling to investigate the effects of the MET inhibitor tepotinib on the TME in a case of locally advanced NSCLC with a METex14 skipping alteration.

Overcoming MET-mediated resistance in oncogene-driven NSCLC.

This study evaluates the efficacy of combining targeted therapies with MET or SHP2 inhibitors to overcome MET-mediated resistance in different NSCLC subtypes. A prevalence study was conducted for MET amplification and overexpression in samples from patients with NSCLC who relapsed on ALK, ROS1, or RET tyrosine kinase inhibitors. MET-mediated resistance was detected in 37.

Improving Delineation of True Tumor Volume With Multimodal MRI in a Rat Model of Brain Metastasis.

Purpose: Brain metastases are almost universally lethal with short median survival times. Despite this, they are often potentially curable, with therapy failing only because of local relapse. One key reason relapse occurs is because treatment planning did not delineate metastasis margins sufficiently or accurately, allowing residual tumor to regrow.

Tumor pH and Protein Concentration Contribute to the Signal of Amide Proton Transfer Magnetic Resonance Imaging.

Abnormal pH is a common feature of malignant tumors and has been associated clinically with suboptimal outcomes. Amide proton transfer magnetic resonance imaging (APT MRI) holds promise as a means to noninvasively measure tumor pH, yet multiple factors collectively make quantification of tumor pH from APT MRI data challenging. The purpose of this study was to improve our understanding of the biophysical sources of altered APT MRI signals in tumors.

Sensitivity of Multiphase Pseudocontinuous Arterial Spin Labelling (MP pCASL) Magnetic Resonance Imaging for Measuring Brain and Tumour Blood Flow in Mice.

Brain and tumour blood flow can be measured noninvasively using arterial spin labelling (ASL) magnetic resonance imaging (MRI), but reliable quantification in mouse models remains difficult. Pseudocontinuous ASL (pCASL) is recommended as the clinical standard for ASL and can be improved using multiphase labelling (MP pCASL). The aim of this study was to optimise and validate MP pCASL MRI for cerebral blood flow (CBF) measurement in mice and to assess its sensitivity to tumour perfusion.

Quantitative blood flow measurement in rat brain with multiphase arterial spin labelling magnetic resonance imaging.

Cerebral blood flow is an important parameter in many diseases and functional studies that can be accurately measured in humans using arterial spin labelling (ASL) MRI. However, although rat models are frequently used for preclinical studies of both human disease and brain function, rat CBF measurements show poor consistency between studies. This lack of reproducibility is due, partly, to the smaller size and differing head geometry of rats compared to humans, as well as the differing analysis methodologies employed and higher field strengths used for preclinical MRI.

PKCι depletion initiates mitotic slippage-induced senescence in glioblastoma.

Cellular senescence is a tumor suppressor mechanism where cells enter a permanent growth arrest following cellular stress. Oncogene-induced senescence (OIS) is induced in non-malignant cells following the expression of an oncogene or inactivation of a tumor suppressor. Previously, we have shown that protein kinase C iota (PKCι) depletion induces cellular senescence in glioblastoma cells in the absence of a detectable DNA damage response.