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PURPOSE: Next-generation sequencing (NGS) has enabled the detection of concomitant driver alterations in non–small cell lung cancer (NSCLC). However, the magnitude and clinical relevance of concomitant drivers remain to be explored. METHODS: We profiled concomitant driver alterations of EGFR + NSCLC by using targeted NGS. The associated genomic and clinical features were analyzed and validated in an independent The Cancer Genome Atlas cohort of patients with EGFR + NSCLC. RESULTS: Out of the total patient population, 334 patients had EGFR mutations along with concomitant driver mutations, comprising 3.09% of the entire cohort. The most frequent co-occurring mutations with sensitizing EGFR mutations include KRAS at 53.9%, followed by ERBB2 at 24.3%, MET at 16.5%, and BRAF at 3.3%. KRAS mutations in concomitant drivers were frequently hyperexchange mutations (25.6% v 8.2%, P <.001), compared with KRAS single drivers. EGFR / ERBB2 drivers exhibited a higher incidence of ERBB2 amplification (40.7% v 16.5%, P <.001) and p.S310F/Y mutations (44.4% v 4.3%, P <.001) compared with ERBB2 alone. EGFR / MET drivers had a higher frequency of MET amplification (71.4% v 43.3%) than MET single drivers. At the genomic level, the median number of additional concurrent mutations was four, with TSC2 (4%), CD274 (1%), and TP53 (63%) being the most frequently coaltered genes in concomitant driver tumors. Interestingly, clonality analysis indicated that EGFR mutations were more likely to occur as clonal events, whereas the codrivers were more often subclonal. Patients with concomitant drivers or with concomitant MET amplification exhibited worse prognosis. CONCLUSION: These findings might aid in the selection of effective therapeutic regimens and facilitate the development of combination therapies. [ABSTRACT FROM AUTHOR]

Polo‐like kinase 1 (PLK1) inhibitor NMS‐P937 is a targeted therapeutic agent with good preclinical efficacy in various human cancers, and its therapeutic effect on nasopharyngeal carcinoma (NPC) remains to be determined. Here, to explore biological activity of NMS‐P937 in NPC, multiple types of NPC cells were utilized. We tested IC50 values, carried out flow cytometry, western blot analysis analysis, immunofluorescence, and constructed subcutaneous xenograft mouse models. We found that treatment with NMS‐P937 increased the proportion of G2/M phase NPC cells, where CyclinB1 expression was upregulated and CyclinE1 expression was downregulated. Besides, NMS‐P937 treatment‐induced NPC cell apoptosis with increased cleavage of PARP and caspase‐3. Mechanistically, NMS‐P937 treatment led to aberrant mitosis, causing increased reactive oxygen species (ROS) levels. ROS scavenger N‐acetylcysteine partially reversed ROS levels induced by NMS‐P937. Furthermore, NMS‐P937 administration restrained NPC xenografts growth in nude mice. Overall, NMS‐P937 suppressed NPC cell proliferation and increased ROS levels, causing cell cycle abnormalities and apoptosis. NMS‐P937 holds great promise as a therapeutic agent for treating nasopharyngeal carcinoma. [ABSTRACT FROM AUTHOR]

Femtosecond laser filament-induced plasma spectroscopy (FIPS) demonstrates great potential in remote sensing for identifying atmospheric pollutant molecules. Due to the widespread aerosols in the atmosphere, remote detection based on FIPS would be affected by both the excitation and the propagation of fingerprint fluorescence, which still remain elusive. Here the physical model of filament-induced aerosol fluorescence is established to reveal the combined effect of Mie scattering and amplification spontaneous emission, which is subsequently proven by experimental results, the dependence of the backward fluorescence on the interaction length between filaments and aerosols. These findings provide an insight into the complicated aerosol effect in the overall physical process of FIPS including propagation, excitation, and emission, paving the way to its practical application in atmospheric remote sensing.