Non-small-cell lung cancer(NSCLC)remains the leading cause of cancer-related death in both men and women in the United States.Platinum-based doublet chemotherapy has been a standard for patients with advanced stage di...Non-small-cell lung cancer(NSCLC)remains the leading cause of cancer-related death in both men and women in the United States.Platinum-based doublet chemotherapy has been a standard for patients with advanced stage disease.Improvements in overall survival and quality of life have been modest.Improved knowledge of the aberrant molecular signaling pathways found in NSCLC has led to the development of biomarkers with associated targeted therapeutics,thus changing the treatment paradigm for many NSCLC patients.In this review,we present a summary of many of the currently investigated biologic targets in NSCLC,discuss their current clinical trial status,and also discuss the potential for development of other targeted agents.展开更多
Background： Drug resistance to targeted therapies occurs in lung cancer, and resistance mechanisms related to epidermal growth factor receptor （EGFR） tyrosine kinase inhibitors （TKIs） are continuously being disco...Background： Drug resistance to targeted therapies occurs in lung cancer, and resistance mechanisms related to epidermal growth factor receptor （EGFR） tyrosine kinase inhibitors （TKIs） are continuously being discovered. We aimed to establish a novel method for highly parallel multiplexed detection of genetic mutations related to EGFR TKl-resistant lung cancer using Agena iPLEX chemistry and niatrix-assisted laser desorption ionization time-of-flight analysis on the MassARRAY mass spectrometry platform. Methods： A review of the literature revealed 60 mutation hotspots in seven target genes （EGFR, KRAS, PIK3CA, BRAF, ERBB2, NRAS, and BIM） that are closely related to EGFR TKI resistance to lung cancer. A total of 183 primers comprised 61 paired forward and reverse amplification primers, and 61 matched extension primers were designed using Assay Design Software. The detection method was established by analyzing nine cell lines, and by comparison with LungCartaTM kit in ten lung cancer specimens. EGFR, KRAS. and BIM genes in all cell lines and clinical samples were subjected to Sanger sequencing for confirming reproducibility. Results： Our data showed that designed panel was a high-throughput and robust tool, allowing genotyping for sixty hotspots in the same run. Moreover, it made efficient use of patient diagnostic samples for a more accurate EGFR TKIs resistance analysis. The proposed method could accurately detect mutations in lung cancer cell lines and clinical specimens, consistent with those obtained by the LungCartaTM kit and Sanger sequencing. We also established a method for detection of large-fragment deletions based on single-base extension technology of MassARRAY platform. Conclusions： We established an effective method for high-throughput detection of genetic mutations related to EGFR TKI resistance based on the MassARRAY platform, which could provide more accurate information for overcoming cancers with de novo or acquired resistance to EGFR-targeted therapies.展开更多
Historically,non-small cell lung cancer(NSCLC) is divided into squamous and nonsquamous subtypes based on histologic features.With a growing number of oncogenic drivers being identified in squamous and nonsquamous NSC...Historically,non-small cell lung cancer(NSCLC) is divided into squamous and nonsquamous subtypes based on histologic features.With a growing number of oncogenic drivers being identified in squamous and nonsquamous NSCLC,this malignancy has been recently divided into several distinct subtypes according to the specific molecular alterations.This new paradigm has substantially highlighted the treatment of advanced NSCLC,shifting it from standard chemotherapy according to specific histologic subtypes to targeted therapy according to specific oncogenic drivers.The application of epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitors(TKIs) in NSCLC patients harboring activating EGFR mutations has been a representative model of precise medicine in the treatment of NSCLC.As the role of EGFR-TKIs in routine management of patients with advanced NSCLC has been well established,this review provides an overview of alternative targeted therapy in the treatment of NSCLC,including EGFR-TKIs for patients with wild-type EGFR NSCLC,as well as other targeted agents either clinical available or in early- to late-stage development.展开更多
文摘Non-small-cell lung cancer(NSCLC)remains the leading cause of cancer-related death in both men and women in the United States.Platinum-based doublet chemotherapy has been a standard for patients with advanced stage disease.Improvements in overall survival and quality of life have been modest.Improved knowledge of the aberrant molecular signaling pathways found in NSCLC has led to the development of biomarkers with associated targeted therapeutics,thus changing the treatment paradigm for many NSCLC patients.In this review,we present a summary of many of the currently investigated biologic targets in NSCLC,discuss their current clinical trial status,and also discuss the potential for development of other targeted agents.
文摘Background： Drug resistance to targeted therapies occurs in lung cancer, and resistance mechanisms related to epidermal growth factor receptor （EGFR） tyrosine kinase inhibitors （TKIs） are continuously being discovered. We aimed to establish a novel method for highly parallel multiplexed detection of genetic mutations related to EGFR TKl-resistant lung cancer using Agena iPLEX chemistry and niatrix-assisted laser desorption ionization time-of-flight analysis on the MassARRAY mass spectrometry platform. Methods： A review of the literature revealed 60 mutation hotspots in seven target genes （EGFR, KRAS, PIK3CA, BRAF, ERBB2, NRAS, and BIM） that are closely related to EGFR TKI resistance to lung cancer. A total of 183 primers comprised 61 paired forward and reverse amplification primers, and 61 matched extension primers were designed using Assay Design Software. The detection method was established by analyzing nine cell lines, and by comparison with LungCartaTM kit in ten lung cancer specimens. EGFR, KRAS. and BIM genes in all cell lines and clinical samples were subjected to Sanger sequencing for confirming reproducibility. Results： Our data showed that designed panel was a high-throughput and robust tool, allowing genotyping for sixty hotspots in the same run. Moreover, it made efficient use of patient diagnostic samples for a more accurate EGFR TKIs resistance analysis. The proposed method could accurately detect mutations in lung cancer cell lines and clinical specimens, consistent with those obtained by the LungCartaTM kit and Sanger sequencing. We also established a method for detection of large-fragment deletions based on single-base extension technology of MassARRAY platform. Conclusions： We established an effective method for high-throughput detection of genetic mutations related to EGFR TKI resistance based on the MassARRAY platform, which could provide more accurate information for overcoming cancers with de novo or acquired resistance to EGFR-targeted therapies.
文摘Historically,non-small cell lung cancer(NSCLC) is divided into squamous and nonsquamous subtypes based on histologic features.With a growing number of oncogenic drivers being identified in squamous and nonsquamous NSCLC,this malignancy has been recently divided into several distinct subtypes according to the specific molecular alterations.This new paradigm has substantially highlighted the treatment of advanced NSCLC,shifting it from standard chemotherapy according to specific histologic subtypes to targeted therapy according to specific oncogenic drivers.The application of epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitors(TKIs) in NSCLC patients harboring activating EGFR mutations has been a representative model of precise medicine in the treatment of NSCLC.As the role of EGFR-TKIs in routine management of patients with advanced NSCLC has been well established,this review provides an overview of alternative targeted therapy in the treatment of NSCLC,including EGFR-TKIs for patients with wild-type EGFR NSCLC,as well as other targeted agents either clinical available or in early- to late-stage development.
