Triple administration of osimertinib followed by chemotherapy for advanced lung adenocarcinoma: A case report

BACKGROUND Osimertinib is the recommended first-line treatment for adult patients with epidermal growth factor receptor(EGFR)mutation positive advanced or metastatic non-small cell lung cancer(NSCLC).However,primary or acquired resistance to EGFR-tyrosine kinase inhibitors(EGFR-TKIs)seems inevitable,and when drug-resistance occurs during treatment with osimertinib,the standard of care is to discontinue the TKI.CASE SUMMARY A 57-year-old female patient with lung adenocarcinoma presented with an irritating cough accompanied by chest distress of one month duration.An enhanced head magnetic resonance imaging scan showed brain metastases.An EGFR mutation(exon 21 L858R)was detected in pleural fluid.The patient was treated with oral osimertinib(80 mg once daily)from January 2018 but developed progressive disease on December 2018.She was then successfully treated with rechallenge and tri-challenge with osimertinib(80 mg once daily)by resensitization chemotherapy twice after the occurrence of drug-resistance to osimertinib,and to date has survived for 31 mo.CONCLUSION This case may provide some selective therapeutic options for NSCLC patients with acquired drug-resistance who were previously controlled on osimertinib treatment.

Pyroptotic macrophages stimulate the SARS-CoV-2-associated cytokine storm

Coronavirus disease 2019(COVID-19)is an unprecedented pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).As of 22 February 2021,the worldwide pandemic has resulted in more than 110 million cases and 2.4 million deaths.1 Clinical investigation of COVID-19 patients has shown that a systemic cytokine storm can occur,especially in severe cases.2 Treatment of the SARS-CoV-2-associated cytokine storm with tocilizumab3 or anakinra4 has been shown to immediately improve the clinical outcome in most severe and critical COVID-19 patients.These data highlight the systemic cytokine storm as an important exacerbating event in severe COVID-19;however,our understanding of the molecular mechanisms involved in the initiation of the SARS-CoV-2-associated cytokine storm is limited.In the present study,we uncovered a reasonable explanation for cytokine storm initiation through the analysis of 13 autopsy samples from severe COVID-19 patients.

Elevated Kir2.1/nuclear N2ICD defines a highly malignant subtype of non-WNT/SHH medulloblastomas

Medulloblastoma(MB)is one of the most common childhood malignant brain tumors(WHO grade IV),traditionally divided into WNT,SHH,Group 3,and Group 4 subgroups based on the transcription profiles,somatic DNA alterations,and clinical outcomes.Unlike WNT and SHH subgroup MBs,Group 3 and Group 4 MBs have similar transcriptomes and lack clearly specific drivers and targeted therapeutic options.The recently revised WHO Classification of CNS Tumors has assigned Group 3 and 4 to a provisional non-WNT/SHH entity.In the present study,we demonstrate that Kir2.1,an inwardly-rectifying potassium channel,is highly expressed in non-WNT/SHH MBs,which promotes tumor cell invasion and metastasis by recruiting Adam10 to enhance S2 cleavage of Notch2 thereby activating the Notch2 signaling pathway.Disruption of the Notch2 pathway markedly inhibited the growth and metastasis of Kir2.1-overexpressing MB cell-derived xenograft tumors in mice.Moreover,Kir2.1^(high)/nuclear N2ICD^(high)MBs are associated with the significantly shorter lifespan of the patients.Thus,Kir2.1^(high)/nuclear N2ICD^(high)can be used as a biomarker to define a novel subtype of non-WNT/SHH MBs.Our findings are important for the modification of treatment regimens and the development of novel-targeted therapies for non-WNT/SHH MBs.