Changing profile of lung cancer clinical characteristics in China:Over 8-year population-based study

Background:Although examinations and therapies for bronchial lung cancer,also called lung cancer(LC),have become more effective and precise,the morbidity and mortality of LC remain high worldwide.Describing the changing profile of LC characteristics over time is indispensable.This study aimed to understand the changes in real-world settings of LC and its characteristics in China.Methods:In this study,119,785 patients were enrolled from 2012 to 2020 in the Shanghai Pulmonary Hospital.The patients’medical records were extracted from the hospital’s database.Demographic characteristics,general clinicopathological information,and blood coagulation indices at the initial diagnoses were analyzed using the Kruskal-Wallis,Nemenyi,chi-squared,and Bonferroni tests.Changes in demographic characteristics during the 8-year study period,namely dynamic changes among different stages and different pathological types,were evaluated.Results:The percentages of female(from 38.50%[323/839]in 2012 to 48.29%[5112/10,585]in 2020)and non-smoking LC(from 69.34%[475/685]to 80.48%[8055/10,009])patients increased significantly during the study period,with a trend toward a younger age at diagnosis(from 3.58%[30/839]to 8.99%[952/10,585]).Over the study period,the proportion and absolute number of lung adenocarcinoma cases increased(from 67.97%[433/637]to 76.31%[6606/8657])while the proportion of lung squamous cell carcinoma decreased(from 21.19%[135/637]to 12.08%[1046/8657]).Comprehensive driver gene mutation examination became more common,and epidermal growth factor receptor(EGFR)mutation occurred more frequently in female vs.male(62.03%[12793/20625]vs.29.90%[8207/27,447])and non-smoking vs.smoking(53.54%[17,203/32,134]vs.23.73%[3322/13,997])patients(both P<0.001).The distribution of the common driver genes differed among different stages of LC.EGFR mutation was detected most frequently at each stage,and other driver gene alterations were more common in advanced stages(P<0.001).The combination of chemotherapy,targeted ther-apy,and immunotherapy,as a comprehensive management regimen,gradually became predominant over the study period(P<0.001).A hypercoagulable state was shown in advanced-stage LC patients and patients with the anaplastic lymphoma kinase fusion,indicated by significantly elevated levels of d-dimer,fibrinogen,and fibrinogen degradation products.Conclusions:This study comprehensively depicted the changing characteristics of Chinese LC patients over an 8-year period to provide preliminary insights into LC treatment.Trial registration:ClinicalTrials.gov,NCT05423236.

Pyroptosis:A promising target for lung cancer therapy

Pyroptosis is a type of programed cell death that differs from apoptosis,ferroptosis,or necrosis.Numerous studies have reported that it plays a critical role in tumorigenesis and modification of the tumor microenvironment in multiple tumors.In this review,we briefly describe the canonical,non-canonical,and alternative mechanisms of pyroptotic cell death.We also summarize the potential roles of pyroptosis in oncogenesis,tumor development,and lung cancer treatment,including chemotherapy,radiotherapy,targeted therapy,and immunotherapy.Pyrop-tosis has double-edged effects on the modulation of the tumor environment and lung cancer treatment.Further exploration of pyroptosis-based drugs could provide novel therapeutic strategies for lung cancer.

Update on lymphocyte-activation gene 3 (LAG-3) in cancers: from biological properties to clinical applications

Immunotherapy that targets checkpoints, especially programmed cell death protein 1 and programmed cell death ligand 1, has revolutionized cancer therapy regimens. The overall response rate to mono-immunotherapy, however, is limited, emphasizing the need to potentiate the efficacy of these regimens. The functions of immune cells are modulated by multiple stimulatory and inhibitory molecules, including lymphocyte activation gene 3 (LAG-3). LAG-3 is co-expressed together with other inhibitory checkpoints and plays key roles in immune suppression. Increasing evidence, particularly in the last 5 years, has shown the potential of LAG-3 blockade in anti-tumor immunity. This review provides an update on the biological properties and clinical applications of LAG-3 in cancers.