BACKGROUND The biochemical phenomenon defined as poly adenosine diphosphate(ADP)-ribosylation(PARylation)is essential for the progression of pancreatic cancer.However,the excessive accumulation of poly ADP-ribose(PAR)...BACKGROUND The biochemical phenomenon defined as poly adenosine diphosphate(ADP)-ribosylation(PARylation)is essential for the progression of pancreatic cancer.However,the excessive accumulation of poly ADP-ribose(PAR)induces apoptosis-inducing factor(AIF)release from mitochondria and energy deprivation resulting in the caspase-independent death of cancer cells.AIM To investigate whether sustained calcium supply could induce an anticancer effect on pancreatic cancer by PAR accumulation.METHODS Two pancreatic cancer cell lines,AsPC-1 and CFPAC-1 were used for the study.Calcium influx and mitochondrial reactive oxygen species(ROS)were observed by fluorescence staining.Changes in enzyme levels,as well as PAR accumulation and energy metabolism,were measured using assay kits.AIF-dependent cell death was investigated followed by confirming in vivo anticancer effects by sustained calcium administration.RESULTS Mitochondrial ROS levels were elevated with increasing calcium influx into pancreatic cancer cells.Then,excess PAR accumulation,decreased PAR glycohydrolase and ADP-ribosyl hydrolase 3 levels,and energy deprivation were observed.In vitro and in vivo antitumor effects were confirmed to accompany elevated AIF levels.CONCLUSION This study visualized the potential anticancer effects of excessive PAR accumulation by sustained calcium supply on pancreatic cancer,however elucidating a clear mode of action remains a challenge,and it should be accompanied by further studies to assess its potential for clinical application.展开更多
目的:系统评价PARPi治疗转移性去势抵抗性前列腺癌(mCRPC)的有效性及安全性,以期为临床决策供循证医学证据。方法:依据纳入和排除标准,网络检索2015年1月~2023年6月PubMed、Web of Science、Embace、Clinicial.gov中有关PARPi治疗mCRPC...目的:系统评价PARPi治疗转移性去势抵抗性前列腺癌(mCRPC)的有效性及安全性,以期为临床决策供循证医学证据。方法:依据纳入和排除标准,网络检索2015年1月~2023年6月PubMed、Web of Science、Embace、Clinicial.gov中有关PARPi治疗mCRPC的随机对照试验文献,使用RevMan5.4及Stata17.0软件对数据进行Meta分析。结果:纳入7篇随机对照试验文献,共1888例患者。Meta分析结果表明,与非PARPi组比较,PARPi组(PARPi联合或不联合抗激素治疗)可提高mCRPC的放射学无进展生存期(HR=0.52,95%CI=0.34~0.78)和总生存期(HR=0.72,95%CI=0.60~0.86),差异均有统计学意义(P<0.05)。在安全性方面,PARPi组1~2级骨痛、背痛、贫血、中性粒细胞减少、恶心、呕吐、腹泻、乏力不良反应发生率明显高于非PARPi组,差异均有统计学意义(P<0.05);≥3级上述不良反应中与非PARPi组比较,PARPi组中只有恶心和贫血不良反应发生率较高,差异均有统计学意义(P<0.05),而骨痛、背痛、中性粒细胞减少、呕吐、腹泻、乏力两组间比较差异均无统计学意义(P>0.05)。结论:与非PARPi比较,PARPi联合或不联合抗激素治疗可提高mCRPC的放射学无进展生存期和总生存期,3级及以上不良反应发生率低,值得在临床上推广应用。展开更多
Metastatic triple negative breast cancer(TNBC)has an aggressive phenotype with a predilection for visceral organs and brain.Best responses to chemotherapy are predominately in the first line.Recent studies have demons...Metastatic triple negative breast cancer(TNBC)has an aggressive phenotype with a predilection for visceral organs and brain.Best responses to chemotherapy are predominately in the first line.Recent studies have demonstrated improved progression free survival with the combination of atezolizumab/pembrolizumab and chemotherapy in programmed death-ligand 1 positive metastatic TNBC.However,a recent trial in a similar population showed no benefit for atezolizumab and paclitaxel which led to a Food and Drug Administration alert.Two phase III trials(OLYMPIAD and BROCADE3)demonstrated a benefit in progression free survival(PFS)but not overall survival in patients with BRCAassociated metastatic TNBC treated with Olaparib or Talazoparib respectively.For those treated with Talazoparib,the time to deterioration in health related-quality of life was also longer compared to chemotherapy.The BROCADE3 trial demonstrated that the combination of a platinum and veliparib increased PFS in first-line metastatic TNBC but at the cost of increased toxicity.There are no headto-head comparisons of a poly(adenosine diphosphate-ribose)polymerase inhibitors(PARPi)and platinums.There are unanswered questions regarding the role of PARPi maintenance after platinum therapy as is standard of care in BRCAassociated ovarian cancer.Other areas of therapeutic interest include targeting aberrations in the phosphoinositide 3-kinase pathway,protein kinase B,mammalian target of rapamycin or utilising antibody drug conjugates.This review focusses on recent and emerging therapeutic options in metastatic TNBC.We searched PubMed,clinicaltrials.gov and recent international meetings from American Society of Clinical Oncology,San Antonio Breast Cancer Conference and the European Society of Medical Oncology.展开更多
Small-cell lung cancer(SCLC)is a special type of lung cancer that belongs to highly aggressive neuroendocrine tumors.At present,radiotherapy and chemotherapy remain the mainstay of treatment for SCLC.Progress in targe...Small-cell lung cancer(SCLC)is a special type of lung cancer that belongs to highly aggressive neuroendocrine tumors.At present,radiotherapy and chemotherapy remain the mainstay of treatment for SCLC.Progress in targeted therapies for SCLC with driver mutations has been slow,and these therapies are still under investigation in preclinical or early-phase clinical trials,and research on antiangiogenic tyrosine kinase inhibitors(e.g.,anlotinib)has achieved some success.Immunotherapy is becoming an important treatment strategy for SCLC after radiotherapy and chemotherapy.In this article we review the recent advances in immunotherapy for SCLC.展开更多
BACKGROUND In recent years,targeted therapy and immunotherapy have become important treatment strategies for patients with non-small cell lung cancer(NSCLC).However,the clinical evidence for successful off-label use o...BACKGROUND In recent years,targeted therapy and immunotherapy have become important treatment strategies for patients with non-small cell lung cancer(NSCLC).However,the clinical evidence for successful off-label use of targeted drugs for patients with NSCLC following progression on multiple lines of treatment is still lacking.CASE SUMMARY We describe a 62-year-old male patient with a right lung adenocarcinoma who harbored an EGFR exon 19 deletion mutation.He received gefitinib combined with six cycles of vinorelbine,cisplatin,and recombinant human endostatin as the first-line therapy.Then gefitinib was administered in combination with recombinant human endostatin as maintenance therapy,resulting in a progression-free survival(PFS)of 14 mo.Chemoradiotherapy was added following progression(enlarged brain metastases)on maintenance treatment.Unfortunately,the brain lesions were highly refractory and progressed again after 15 mo,at which time next-generation sequencing(NGS)of 1021 cancer-related genes was performed using peripheral blood to identify potential actionable mutations.NGS revealed that the patient harbored a BRCA2 germline mutation,the EGFR exon 19 deletion mutation disappeared,and no additional targetable genetic variant was detected.Therefore,the patient received olaparib combined with gefitinib and recombinant human endostatin,with a rapid and long-lasting clinical response(PFS=13.5 mo).CONCLUSION This is a rare case of lung adenocarcinoma in a patient with a BRCA2 germline mutation who had long-term benefit from olaparib combination treatment,suggesting that NGS-based genetic testing may render the possibility of long-term survival in NSCLC patients after disease progression.展开更多
文摘BACKGROUND The biochemical phenomenon defined as poly adenosine diphosphate(ADP)-ribosylation(PARylation)is essential for the progression of pancreatic cancer.However,the excessive accumulation of poly ADP-ribose(PAR)induces apoptosis-inducing factor(AIF)release from mitochondria and energy deprivation resulting in the caspase-independent death of cancer cells.AIM To investigate whether sustained calcium supply could induce an anticancer effect on pancreatic cancer by PAR accumulation.METHODS Two pancreatic cancer cell lines,AsPC-1 and CFPAC-1 were used for the study.Calcium influx and mitochondrial reactive oxygen species(ROS)were observed by fluorescence staining.Changes in enzyme levels,as well as PAR accumulation and energy metabolism,were measured using assay kits.AIF-dependent cell death was investigated followed by confirming in vivo anticancer effects by sustained calcium administration.RESULTS Mitochondrial ROS levels were elevated with increasing calcium influx into pancreatic cancer cells.Then,excess PAR accumulation,decreased PAR glycohydrolase and ADP-ribosyl hydrolase 3 levels,and energy deprivation were observed.In vitro and in vivo antitumor effects were confirmed to accompany elevated AIF levels.CONCLUSION This study visualized the potential anticancer effects of excessive PAR accumulation by sustained calcium supply on pancreatic cancer,however elucidating a clear mode of action remains a challenge,and it should be accompanied by further studies to assess its potential for clinical application.
文摘目的:系统评价PARPi治疗转移性去势抵抗性前列腺癌(mCRPC)的有效性及安全性,以期为临床决策供循证医学证据。方法:依据纳入和排除标准,网络检索2015年1月~2023年6月PubMed、Web of Science、Embace、Clinicial.gov中有关PARPi治疗mCRPC的随机对照试验文献,使用RevMan5.4及Stata17.0软件对数据进行Meta分析。结果:纳入7篇随机对照试验文献,共1888例患者。Meta分析结果表明,与非PARPi组比较,PARPi组(PARPi联合或不联合抗激素治疗)可提高mCRPC的放射学无进展生存期(HR=0.52,95%CI=0.34~0.78)和总生存期(HR=0.72,95%CI=0.60~0.86),差异均有统计学意义(P<0.05)。在安全性方面,PARPi组1~2级骨痛、背痛、贫血、中性粒细胞减少、恶心、呕吐、腹泻、乏力不良反应发生率明显高于非PARPi组,差异均有统计学意义(P<0.05);≥3级上述不良反应中与非PARPi组比较,PARPi组中只有恶心和贫血不良反应发生率较高,差异均有统计学意义(P<0.05),而骨痛、背痛、中性粒细胞减少、呕吐、腹泻、乏力两组间比较差异均无统计学意义(P>0.05)。结论:与非PARPi比较,PARPi联合或不联合抗激素治疗可提高mCRPC的放射学无进展生存期和总生存期,3级及以上不良反应发生率低,值得在临床上推广应用。
文摘Metastatic triple negative breast cancer(TNBC)has an aggressive phenotype with a predilection for visceral organs and brain.Best responses to chemotherapy are predominately in the first line.Recent studies have demonstrated improved progression free survival with the combination of atezolizumab/pembrolizumab and chemotherapy in programmed death-ligand 1 positive metastatic TNBC.However,a recent trial in a similar population showed no benefit for atezolizumab and paclitaxel which led to a Food and Drug Administration alert.Two phase III trials(OLYMPIAD and BROCADE3)demonstrated a benefit in progression free survival(PFS)but not overall survival in patients with BRCAassociated metastatic TNBC treated with Olaparib or Talazoparib respectively.For those treated with Talazoparib,the time to deterioration in health related-quality of life was also longer compared to chemotherapy.The BROCADE3 trial demonstrated that the combination of a platinum and veliparib increased PFS in first-line metastatic TNBC but at the cost of increased toxicity.There are no headto-head comparisons of a poly(adenosine diphosphate-ribose)polymerase inhibitors(PARPi)and platinums.There are unanswered questions regarding the role of PARPi maintenance after platinum therapy as is standard of care in BRCAassociated ovarian cancer.Other areas of therapeutic interest include targeting aberrations in the phosphoinositide 3-kinase pathway,protein kinase B,mammalian target of rapamycin or utilising antibody drug conjugates.This review focusses on recent and emerging therapeutic options in metastatic TNBC.We searched PubMed,clinicaltrials.gov and recent international meetings from American Society of Clinical Oncology,San Antonio Breast Cancer Conference and the European Society of Medical Oncology.
文摘Small-cell lung cancer(SCLC)is a special type of lung cancer that belongs to highly aggressive neuroendocrine tumors.At present,radiotherapy and chemotherapy remain the mainstay of treatment for SCLC.Progress in targeted therapies for SCLC with driver mutations has been slow,and these therapies are still under investigation in preclinical or early-phase clinical trials,and research on antiangiogenic tyrosine kinase inhibitors(e.g.,anlotinib)has achieved some success.Immunotherapy is becoming an important treatment strategy for SCLC after radiotherapy and chemotherapy.In this article we review the recent advances in immunotherapy for SCLC.
文摘BACKGROUND In recent years,targeted therapy and immunotherapy have become important treatment strategies for patients with non-small cell lung cancer(NSCLC).However,the clinical evidence for successful off-label use of targeted drugs for patients with NSCLC following progression on multiple lines of treatment is still lacking.CASE SUMMARY We describe a 62-year-old male patient with a right lung adenocarcinoma who harbored an EGFR exon 19 deletion mutation.He received gefitinib combined with six cycles of vinorelbine,cisplatin,and recombinant human endostatin as the first-line therapy.Then gefitinib was administered in combination with recombinant human endostatin as maintenance therapy,resulting in a progression-free survival(PFS)of 14 mo.Chemoradiotherapy was added following progression(enlarged brain metastases)on maintenance treatment.Unfortunately,the brain lesions were highly refractory and progressed again after 15 mo,at which time next-generation sequencing(NGS)of 1021 cancer-related genes was performed using peripheral blood to identify potential actionable mutations.NGS revealed that the patient harbored a BRCA2 germline mutation,the EGFR exon 19 deletion mutation disappeared,and no additional targetable genetic variant was detected.Therefore,the patient received olaparib combined with gefitinib and recombinant human endostatin,with a rapid and long-lasting clinical response(PFS=13.5 mo).CONCLUSION This is a rare case of lung adenocarcinoma in a patient with a BRCA2 germline mutation who had long-term benefit from olaparib combination treatment,suggesting that NGS-based genetic testing may render the possibility of long-term survival in NSCLC patients after disease progression.
