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2篇 您的检索式:作者名="Luis E.Raez"
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1Importance of ROS1 gene fusions in non-small cell lung cancer显示文摘Targeted therapy has become one of the standards of care for advanced lung cancer.More than 10 genetic aberrations have been discovered that are actionable and several tyrosine kinase inhibitors(TKIs)have been approved to target each of them.Among several genetic aberrations that are actionable in non-small cell lung cancer(NSCLC),ROS1 translocations also known as gene fusion proteins,are found in only 1%-2%of the patient population.ROS1 mutations can usually be detected using a combination of techniques such as immunohistochemistry(IHC),Fluorescence in-situ testing(FISH),polymerase chain reaction(PCR),and nextgeneration sequencing(NGS).However,RNA NGS and ctDNA NGS(liquid biopsies)also contribute to the diagnosis.There are currently numerous FDA-approved agents for these tumors,including crizotinib and entrectinib;however,there is in-vitro sensitivity data and clinical data documenting responses to ceritinib and lorlatinib.Clinical responses and survival rates with these agents are frequently among the best compared to other TKIs with genetic aberrations;however,intrinsic or extrinsic mechanisms of resistance may develop,necessitating research for alternative treatment modalities.To combat the mechanisms of resistance,novel agents such as repotrectenib,cabozantinib,talotrectinib,and others are being developed.In this article,we examine the literature pertaining to patients with ROS1 tumors,including epidemiology,clinical outcomes,resistance mechanisms,and treatment options.Meri Muminovic Carlos Rodrigo Carracedo Uribe Andres Alvarez-Pinzon Khine Shan Luis E.Raez 2023Cancer Drug Resistance2023,6,2:0
2Using cfRNA as a tool to evaluate clinical treatment outcomes in patients with metastatic lung cancers and other tumors显示文摘Aim:We report an exploratory analysis of cfRNA as a biomarker to monitor clinical responses in non-small cell lung cancer(NSCLC),breast cancer,and colorectal cancer(CRC).An analysis of cfRNA as a method for measuring PD-L1 expression with comparison to clinical responses was also performed in the NSCLC cohort.Methods:Blood samples were collected from 127 patients with metastatic disease that were undergoing therapy,52 with NSCLC,50 with breast cancer,and 25 with CRC.cfRNA was purified from fractionated plasma,and following reverse transcription(RT),total cfRNA and gene expression of PD-L1were analyzed by real-time polymerase chain reaction(qPCR)using beta-actin expression as a surrogate for relative amounts of cfDNA and cfRNA.For the concordance study of liquid biopsies and tissue biopsies,the isolated RNA was analyzed by RNAseq for the expressions of 13 genes.We had to close the study early due to a lack of follow-up during the Covid-19 pandemic.Results:We collected a total of 373 blood samples.Mean cfRNA PCR signals after RT were about 50-fold higher than those of cfDNA.cfRNA was detected in all patients,while cfDNA was detected in 88%of them.A high concordance was found for the expression levels of 13 genes between blood and solid tumor tissue.Changes in cfRNA levels followed over the course of treatments were associated with response to therapy,increasing in progressive disease(PD)and falling when a partial response(PR)occurred.The expression of PD-L1 over time in patients treated with immunotherapy decreased with PR but increased with PD.Pre-treatment levels of PD-L1 were predictive of response in patients treated with immunotherapy.Conclusion:Changes in cfRNA correlate with clinical response to the therapy.Total cfRNA may be useful in predicting clinical outcomes.PD-L1 gene expression may provide a biomarker to predict response to PD-L1 inhibition.Luis E.Raez Kathleen Danenberg Daniel Sumarriva Joshua Usher Jacob Sands Aurelio Castrellon Pablo Ferraro Adriana Milillo Eric Huang Patrick Soon-Shiong Sandeep Reddy Peter Danenberg 2021Cancer Drug Resistance2021,4,4:0
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