Heterogeneity within the solid tumor microenvironment contributes to a poor prognosis and limited therapeutic responses.Companion diagnostics(CDx),a clinical technique that gives doctors vital biomarker information to...Heterogeneity within the solid tumor microenvironment contributes to a poor prognosis and limited therapeutic responses.Companion diagnostics(CDx),a clinical technique that gives doctors vital biomarker information to enhance patient outcomes through matching specific treatments to patients,is becoming more and more important.However,most current US Food and Drug Administration(FDA)-approved CDx tests have difficulty dynamically reflecting variations in biomarkers in the solid tumor microenvironment because they are used in vitro and ex vivo.Consequently,new medical imaging-based CDx tests have been widely used to detect interpatient and intrapatient tumor heterogeneity to assess the intratumoral distribution of specific biomarkers and microenvironment variables.They provide patient stratification for targeted therapies and the differentiation of patient populations that benefit from alternative treatments.This review provides an overview of the recent advances in medical imaging-based CDx for solid tumors and summarizes the various tumor microenvironment biomarkers utilized in imaging-based CDx.We believe that this review offers additional details and directions for promoting medical imaging-based CDx development.展开更多
To fully implement precision medicine,a deeper understanding of biomarkers,companion diagnostics,and their use in clinical trials is needed.Here,we describe key events in biomarker discovery and clinical trial design,...To fully implement precision medicine,a deeper understanding of biomarkers,companion diagnostics,and their use in clinical trials is needed.Here,we describe key events in biomarker discovery and clinical trial design,and how those stages may be streamlined to fast-track approval of companion diagnostics(CDx).We discuss crucial qualities of a successful CDx that include understanding the prevalence of the marker in the intention to treat population,careful consideration of the scoring scheme that will be used in later clinical trial stages,and reliability of the performance of the CDx,in addition to other necessary features.展开更多
Tumor heterogeneity has increasingly underscored the urgent need for personalized medicine,prompting the Food and Drug Administration(FDA)to approve in vitro companion diagnostics(CDx)for patient stratification.This e...Tumor heterogeneity has increasingly underscored the urgent need for personalized medicine,prompting the Food and Drug Administration(FDA)to approve in vitro companion diagnostics(CDx)for patient stratification.This evolving landscape has gradually transitioned towards imagingbased CDx,which is now further integrated with therapeutic modalities,culminating in the emergence of companion theranostics(CTx).In this review,we systematically elucidate the development of CTx and provide the first formal definition of this concept,thereby establishing a clear framework that distinguishes it from existing diagnostic approaches.We particularly emphasize the design principles underlying CTx by introducing activation strategies that leverage tumor active markers and treatmentactivation mechanisms to enhance therapeutic precision.Finally,we address key challenges that remain,including the markers discovery,fine-tuning probes design,and regulatory approvals for clinical applications.We hope the insights shared in this review will contribute to the design of CTx for oncology,advancing personalized medicine.展开更多
Amplification of the human epidermal growth factor receptor 2 (HER2) gene and overexpression of the HER2 protein is found in 15%-20% of patients with gastric and gastroesophageal junction cancer. The degree of HER2 ov...Amplification of the human epidermal growth factor receptor 2 (HER2) gene and overexpression of the HER2 protein is found in 15%-20% of patients with gastric and gastroesophageal junction cancer. The degree of HER2 overexpression and amplification varies with the location of the carcinoma, with higher expression in the gastroesophageal and proximal parts compared to the distal parts of the stomach. Further, HER2 overexpression and amplification also seems to be related to the Lauren histological classification, with higher levels found in the intestinal phenotype compared to the diffuse and mixed types. The prognostic properties of HER2 overexpression and amplification are still under debate, but a large number of studies seem to indicate that HER2 is a negative prognostic factor. The usefulness of HER2 targeted therapy in gastric cancer was demonstrated in the ToGA trial, where HER2-positive patients with advanced gastric and gastroesophageal junction adenocarcinoma were randomized to receive 5-FU/capecitabine and cisplatin, either alone or in combination with trastuzumab. A statically significant gain in overall survival was seen in patients who received the combined treatment of trastuzumab and chemotherapy. Patients with a strong overexpression of the HER2 protein (IHC3+) specifically benefited from the treatment, with a median overall survival of 17.9 mo. As a consequence of the positive results of the ToGA trial, patients with advanced gastric or gastroesophageal junction adenocarcinoma are now routinely tested for HER2. The ToGA trial must be characterized as a landmark in the treatment of gastric cancer and it has paved the way for a number of new HER2 targeted compounds such as pertuzumab, ado-trastuzumab emtansine, lapatinib, afatinib, and dacomitinib, which are currently undergoing phase II and III clinical testing. Overall, this review will discuss the current status of HER2 in gastric and gastroesophageal junction cancer and the future direction in relation to HER2 target therapy.展开更多
基金supported by the National Natural Science Foundation of China[grant number U21A20287]the Shenzhen Science and Technology Program[grant number JCYJ20210324140205013].
文摘Heterogeneity within the solid tumor microenvironment contributes to a poor prognosis and limited therapeutic responses.Companion diagnostics(CDx),a clinical technique that gives doctors vital biomarker information to enhance patient outcomes through matching specific treatments to patients,is becoming more and more important.However,most current US Food and Drug Administration(FDA)-approved CDx tests have difficulty dynamically reflecting variations in biomarkers in the solid tumor microenvironment because they are used in vitro and ex vivo.Consequently,new medical imaging-based CDx tests have been widely used to detect interpatient and intrapatient tumor heterogeneity to assess the intratumoral distribution of specific biomarkers and microenvironment variables.They provide patient stratification for targeted therapies and the differentiation of patient populations that benefit from alternative treatments.This review provides an overview of the recent advances in medical imaging-based CDx for solid tumors and summarizes the various tumor microenvironment biomarkers utilized in imaging-based CDx.We believe that this review offers additional details and directions for promoting medical imaging-based CDx development.
文摘To fully implement precision medicine,a deeper understanding of biomarkers,companion diagnostics,and their use in clinical trials is needed.Here,we describe key events in biomarker discovery and clinical trial design,and how those stages may be streamlined to fast-track approval of companion diagnostics(CDx).We discuss crucial qualities of a successful CDx that include understanding the prevalence of the marker in the intention to treat population,careful consideration of the scoring scheme that will be used in later clinical trial stages,and reliability of the performance of the CDx,in addition to other necessary features.
基金supported by the National Natural Science Foundation of China(No.82372116)China Postdoctoral Science Foundation(No.2023M742404)+2 种基金Postdoctoral Fellowship Program of CPS Funder(No.GZB20230449)Shenzhen Science and Technology Program(Nos.JCYJ20220818095806014 and KQTD20190929172538530)Research Team Cultivation Program of Shenzhen University(No.2023QNT019).
文摘Tumor heterogeneity has increasingly underscored the urgent need for personalized medicine,prompting the Food and Drug Administration(FDA)to approve in vitro companion diagnostics(CDx)for patient stratification.This evolving landscape has gradually transitioned towards imagingbased CDx,which is now further integrated with therapeutic modalities,culminating in the emergence of companion theranostics(CTx).In this review,we systematically elucidate the development of CTx and provide the first formal definition of this concept,thereby establishing a clear framework that distinguishes it from existing diagnostic approaches.We particularly emphasize the design principles underlying CTx by introducing activation strategies that leverage tumor active markers and treatmentactivation mechanisms to enhance therapeutic precision.Finally,we address key challenges that remain,including the markers discovery,fine-tuning probes design,and regulatory approvals for clinical applications.We hope the insights shared in this review will contribute to the design of CTx for oncology,advancing personalized medicine.
文摘Amplification of the human epidermal growth factor receptor 2 (HER2) gene and overexpression of the HER2 protein is found in 15%-20% of patients with gastric and gastroesophageal junction cancer. The degree of HER2 overexpression and amplification varies with the location of the carcinoma, with higher expression in the gastroesophageal and proximal parts compared to the distal parts of the stomach. Further, HER2 overexpression and amplification also seems to be related to the Lauren histological classification, with higher levels found in the intestinal phenotype compared to the diffuse and mixed types. The prognostic properties of HER2 overexpression and amplification are still under debate, but a large number of studies seem to indicate that HER2 is a negative prognostic factor. The usefulness of HER2 targeted therapy in gastric cancer was demonstrated in the ToGA trial, where HER2-positive patients with advanced gastric and gastroesophageal junction adenocarcinoma were randomized to receive 5-FU/capecitabine and cisplatin, either alone or in combination with trastuzumab. A statically significant gain in overall survival was seen in patients who received the combined treatment of trastuzumab and chemotherapy. Patients with a strong overexpression of the HER2 protein (IHC3+) specifically benefited from the treatment, with a median overall survival of 17.9 mo. As a consequence of the positive results of the ToGA trial, patients with advanced gastric or gastroesophageal junction adenocarcinoma are now routinely tested for HER2. The ToGA trial must be characterized as a landmark in the treatment of gastric cancer and it has paved the way for a number of new HER2 targeted compounds such as pertuzumab, ado-trastuzumab emtansine, lapatinib, afatinib, and dacomitinib, which are currently undergoing phase II and III clinical testing. Overall, this review will discuss the current status of HER2 in gastric and gastroesophageal junction cancer and the future direction in relation to HER2 target therapy.
