Tumorigenesis is a multistep process,with oncogenic mutations in a normal cell conferring clonal advantage as the initial event.However,despite pervasive somatic mutations and clonal expansion in normal tissues,their ...Tumorigenesis is a multistep process,with oncogenic mutations in a normal cell conferring clonal advantage as the initial event.However,despite pervasive somatic mutations and clonal expansion in normal tissues,their transformation into cancer remains a rare event,indicating the presence of additional driver events for progression to an irreversible,highly heterogeneous,and invasive lesion.Recently,researchers are emphasizing the mechanisms of environmental tumor risk factors and epigenetic alterations that are profoundly influencing early clonal expansion and malignant evolution,independently of inducing mutations.Additionally,clonal evolution in tumorigenesis reflects a multifaceted interplay between cell-intrinsic identities and various cell-extrinsic factors that exert selective pressures to either restrain uncontrolled proliferation or allow specific clones to progress into tumors.However,the mechanisms by which driver events induce both intrinsic cellular competency and remodel environmental stress to facilitate malignant transformation are not fully understood.In this review,we summarize the genetic,epigenetic,and external driver events,and their effects on the co-evolution of the transformed cells and their ecosystem during tumor initiation and early malignant evolution.A deeper understanding of the earliest molecular events holds promise for translational applications,predicting individuals at high-risk of tumor and developing strategies to intercept malignant transformation.展开更多
Background:Small-cell lung cancer(SCLC)is characterized by its high malignancy and is associated with a poor prognosis.In the early stages of the disease,platinum-based chemotherapy is the recommended first-line treat...Background:Small-cell lung cancer(SCLC)is characterized by its high malignancy and is associated with a poor prognosis.In the early stages of the disease,platinum-based chemotherapy is the recommended first-line treatment and has demonstrated efficacy.However,SCLC is prone to recurrence and is generally resistant to chemotherapy in its later stages.Methods:Here,we collected samples from SCLC patients who received platinum-based chemotherapy,performed genomic and transcriptomic analyses,and validated our results with publicly available data.Results:SCLC patients with DNA polymerase binding pathway mutations had an improved prognosis after platinum chemotherapy compared with patients without such mutations.Patients in the mutant(MT)group had higher infiltration of T cells,B cells,and M1 macrophages compared with patients without DNA polymerase binding pathway mutations.Conclusions:DNA polymerase binding pathway mutations can be used as prognostic markers for platinum-based chemotherapy in SCLC.展开更多
Existing epidemiologic and clinical studies have demonstrated that obesity is associated with the risk of a variety of cancers.In recent years,an increasing number of experimental and clinical studies have unraveled t...Existing epidemiologic and clinical studies have demonstrated that obesity is associated with the risk of a variety of cancers.In recent years,an increasing number of experimental and clinical studies have unraveled the complex relationship between obesity and cancer risk and the underlying mechanisms.Obesity-induced abnormalities in immunity and biochemical metabolism,including chronic inflammation,hormonal disorders,dysregulation of adipokines,and microbial dysbiosis,may be important contributors to cancer development and progression.These contributors play different roles in cancer development and progression at different sites.Lifestyle changes,weight loss medications,and bariatric surgery are key approaches for weight-centered,obesity-related cancer prevention.Treatment of obesity-related inflammation and hormonal or metabolic dysregulation with medications has also shown promise in preventing obesity-related cancers.In this review,we summarize the mechanisms through which obesity affects the risk of cancer at different sites and explore intervention strategies for the prevention of obesity-associated cancers,concluding with unresolved questions and future directions regarding the link between obesity and cancer.The aim is to provide valuable theoretical foundations and insights for the in-depth exploration of the complex relationship between obesity and cancer risk and its clinical applications.展开更多
基金supported by the National Natural Science Foundation of China(81988101 to D.L.and to C.W.,82203156 to S.Z.)National Key Research and Development Program of China(2021YFC2501000 to D.L.,2023YFC3503200 to S.Z.)+1 种基金Medical and Health Technology Innovation Project of Chinese Academy of Medical Sciences(2021-I2M-1-013 to D.L.and to C.W.,2022-I2M-2-003 to D.L.)Beijing Outstanding Young Scientist Program(BJJWZYJH01201910023027 to C.W.).
文摘Tumorigenesis is a multistep process,with oncogenic mutations in a normal cell conferring clonal advantage as the initial event.However,despite pervasive somatic mutations and clonal expansion in normal tissues,their transformation into cancer remains a rare event,indicating the presence of additional driver events for progression to an irreversible,highly heterogeneous,and invasive lesion.Recently,researchers are emphasizing the mechanisms of environmental tumor risk factors and epigenetic alterations that are profoundly influencing early clonal expansion and malignant evolution,independently of inducing mutations.Additionally,clonal evolution in tumorigenesis reflects a multifaceted interplay between cell-intrinsic identities and various cell-extrinsic factors that exert selective pressures to either restrain uncontrolled proliferation or allow specific clones to progress into tumors.However,the mechanisms by which driver events induce both intrinsic cellular competency and remodel environmental stress to facilitate malignant transformation are not fully understood.In this review,we summarize the genetic,epigenetic,and external driver events,and their effects on the co-evolution of the transformed cells and their ecosystem during tumor initiation and early malignant evolution.A deeper understanding of the earliest molecular events holds promise for translational applications,predicting individuals at high-risk of tumor and developing strategies to intercept malignant transformation.
基金National Natural Science Foundation of China,Grant/Award Numbers:81772457,81802257,81871859,82172750,82172811Natural Science Foundation of Guangdong Province,Grant/Award Numbers:2018A030313846,2021A1515012593。
文摘Background:Small-cell lung cancer(SCLC)is characterized by its high malignancy and is associated with a poor prognosis.In the early stages of the disease,platinum-based chemotherapy is the recommended first-line treatment and has demonstrated efficacy.However,SCLC is prone to recurrence and is generally resistant to chemotherapy in its later stages.Methods:Here,we collected samples from SCLC patients who received platinum-based chemotherapy,performed genomic and transcriptomic analyses,and validated our results with publicly available data.Results:SCLC patients with DNA polymerase binding pathway mutations had an improved prognosis after platinum chemotherapy compared with patients without such mutations.Patients in the mutant(MT)group had higher infiltration of T cells,B cells,and M1 macrophages compared with patients without DNA polymerase binding pathway mutations.Conclusions:DNA polymerase binding pathway mutations can be used as prognostic markers for platinum-based chemotherapy in SCLC.
基金supported by Macao Science and Technology Development Fund(FDCT)grants 0073/2021/A2,and 0009/2022/AKP to K.M.,Research Institute of Tsinghua,Pearl River Delta,ITPRD GBA Innovation Center.
文摘Existing epidemiologic and clinical studies have demonstrated that obesity is associated with the risk of a variety of cancers.In recent years,an increasing number of experimental and clinical studies have unraveled the complex relationship between obesity and cancer risk and the underlying mechanisms.Obesity-induced abnormalities in immunity and biochemical metabolism,including chronic inflammation,hormonal disorders,dysregulation of adipokines,and microbial dysbiosis,may be important contributors to cancer development and progression.These contributors play different roles in cancer development and progression at different sites.Lifestyle changes,weight loss medications,and bariatric surgery are key approaches for weight-centered,obesity-related cancer prevention.Treatment of obesity-related inflammation and hormonal or metabolic dysregulation with medications has also shown promise in preventing obesity-related cancers.In this review,we summarize the mechanisms through which obesity affects the risk of cancer at different sites and explore intervention strategies for the prevention of obesity-associated cancers,concluding with unresolved questions and future directions regarding the link between obesity and cancer.The aim is to provide valuable theoretical foundations and insights for the in-depth exploration of the complex relationship between obesity and cancer risk and its clinical applications.
