Angiotensin converting enzyme 2 (ACE2): Virus accomplice or host defender

The current coronavirus disease-19 (COVID-19) caused by the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has seriously disrupted the daily life of human, mainly attributed to the fact that we know too little about SARS-CoV-2. Increasing studies show that viral infection alters host cells glucose metabolism, which is crucial for viral nucleic acid replication. Here, we integrated RNA-sequencing results and found that SARS-CoV-2 infection alters the aerobic glycolysis, pentose phosphate pathway (oxiPPP), and DNA replication in lung tissues and cells. However, the direction of metabolic flux and DNA replication were dominated by angiotensin-converting enzyme 2 (ACE2), a host cell-expressed viral receptor protein. More interesting, although hosts with high expression of ACE2 are more likely to be infected with SARS-CoV-2, the invading virus cannot perform nucleic acid replication well due to the restriction of glucose metabolism, and eventually resulting prolonged infection-cycle or infection failure. Our findings, after a typical epidemiological investigation and modeling analysis, preliminarily explain the reasons for the emergence of asymptomatic infections or lower copy virus at early stage in host with higher ACE2 levels, which will provide important help for the development of more accurate and effective detection methods for diagnosing COVID-19. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=103 SRC="FIGDIR/small/483197v1_ufig1.gif" ALT="Figure 1"> View larger version (70K): org.highwire.dtl.DTLVardef@b51fcforg.highwire.dtl.DTLVardef@13b7f9corg.highwire.dtl.DTLVardef@136fe46org.highwire.dtl.DTLVardef@16fc92a_HPS_FORMAT_FIGEXP M_FIG C_FIG

Clinical Trial Progress and Application of Immune Checkpoint Inhibitors in the Treatment of Small Cell Lung Cancer / 中国肺癌杂志

Small cell lung cancer (SCLC) is a neuroendocrine tumor with fast progression, high malignancy, easy recurrence, and extremely poor prognosis. In the past 30 years, the clinical treatment strategy of SCLC has been mainly chemotherapy and radiotherapy, but the curative effect is not significant; the current immunotherapy of SCLC has gradually entered the clinic and has made certain progress. Tumor immunotherapy includes immune checkpoint inhibitors, tumor vaccines, cytokines, chimeric antigen receptor T-cell immunotherapy (CAR-T) therapy, etc. Currently, immune checkpoint inhibitors are the most widely used. This article summarizes the principles of immune checkpoint inhibitors and related drugs, summarizes their domestic and foreign clinical trials progress in SCLC treatment, reviews the biomarkers used in the therapy, and discusses its future development direction.
.

Advances in Molecular Typing of Small Cell Lung Cancer / 中国肺癌杂志

Small cell lung cancer (SCLC) is a highly aggressive and fatal malignant tumor. It has the characteristics of complex etiology, low differentiation, high malignancy, fast growth, strong invasiveness, early metastasis and acquired drug resistance, resulting in poor prognosis. In recent years, with the gradual deepening understanding on the molecular mechanism of SCLC and multi-omics data, it is proposed that molecular typing can be carried out according to the differential expression of key transcription factors, including SCLC-A, SCLC-N, SCLC-P and SCLC-I subtypes. Molecular typing of SCLC and its clinical application will help doctors to further optimize the detailed diagnosis and treatment plan of SCLC patients, so as to prolong the survival time and improve the quality of life of patients.
.