Durable response to afatinib in advanced lung adenocarcinoma harboring a novel NPTN-NRG1 fusion: a case report.

BACKGROUND: NRG1 fusions are rare oncogenic drivers in solid tumors, and the incidence of NRG1 fusions in non-small cell lung cancer (NSCLC) was 0.26%. It is essential to explore potential therapeutic strategies and efficacy predictors for NRG1 fusion-positive cancers. CASE PRESENTATION: We report an advanced lung adenocarcinoma patient harboring a novel NPTN-NRG1 fusion identified by RNA-based next-generation sequencing (NGS), which was not detected by DNA-based NGS at initial diagnosis. Transcriptomics data of the tissue biopsy showed NRG1α isoform accounted for 30% of total NRG1 reads, and NRG1ß isoform was undetectable. The patient received afatinib as fourth-line treatment and received a progression-free survival (PFS) of 14 months. CONCLUSIONS: This report supports afatinib can provide potential benefit for NRG1 fusion patients, and RNA-based NGS is an accurate and cost-effective strategy for fusion detection and isoform identification.

A Brain-Targeting NIR-II Ferroptosis System: Effective Visualization and Oncotherapy for Orthotopic Glioblastoma.

Near-infrared-II (NIR-II) ferroptosis activators offer promising potentials in in vivo theranostics of deep tumors, such as glioma. However, most cases are nonvisual iron-based systems that are blind for in vivo precise theranostic study. Additionally, the iron species and their associated nonspecific activations might trigger undesired detrimental effects on normal cells. Considering gold (Au) is an essential cofactor for life and it can specifically bind to tumor cells, Au(I)-based NIR-II ferroptosis nanoparticles (TBTP-Au NPs) for brain-targeted orthotopic glioblastoma theranostics are innovatively constructed. It achieves the real-time visual monitoring of both the BBB penetration and the glioblastoma targeting processes. Moreover, it is first validated that the released TBTP-Au specifically activates the effective heme oxygenase-1-regulated ferroptosis of glioma cells to greatly extend the survival time of glioma-bearing mice. This new ferroptosis mechanism based on Au(I) may open a new way for the fabrication of advanced and high-specificity visual anticancer drugs for clinical trials.

Brain-Targeted Aggregation-Induced-Emission Nanoparticles with Near-Infrared Imaging at 1550 nm Boosts Orthotopic Glioblastoma Theranostics.

A remaining challenge in the treatment of glioblastoma multiforme (GBM) is surmounting the blood-brain barrier (BBB). Such a challenge prevents the development of efficient theranostic approaches that combine reliable diagnosis with targeted therapy. In this study, brain-targeted near-infrared IIb (NIR-IIb) aggregation-induced-emission (AIE) nanoparticles are developed via rational design, which involves twisting the planar molecular backbone with steric hindrance. The resulting nanoparticles can balance competing responsiveness demands for radiation-mediated NIR fluorescence imaging at 1550 nm and non-radiation NIR photothermal therapy (NIR-PTT). The brain-targeting peptide apolipoprotein E peptide (ApoE) is grafted onto these nanoparticles (termed as ApoE-Ph NPs) to target glioma and promote efficient BBB traversal. A long imaging wavelength 1550 nm band-pass filter is utilized to monitor the in vivo biodistribution and accumulation of the nanoparticles in a model of orthotopic glioma, which overcomes previous limitations in wavelength range and equipment. The results demonstrate that the ApoE-Ph NPs have a higher PTT efficiency and significantly enhanced survival of mice bearing orthotopic GBM with moderate irradiation (0.5 W cm-2 ). Collectively, the work highlights the smart design of a brain-targeted NIR-II AIE theranostic approach that opens new diagnosis and treatment options in the photonic therapy of GBM.