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
Traditional antitumor strategies often require sufficient time to assess the effectiveness according to changes in tumor structure.Once ineffective,patients may miss the critical window for pursuing alternative treatm...Traditional antitumor strategies often require sufficient time to assess the effectiveness according to changes in tumor structure.Once ineffective,patients may miss the critical window for pursuing alternative treatment options.Herein,a manganese sulfide nanoplatform loaded with proton pump inhibitor(PPI)is developed.This nanoplatform is designed for visualizing tumor acidosis degree by magnetic resonance imaging(MRI),achieving real-time therapeutic efficacy precognition.The nanoplatform releases PPI,H2S,and Mn2+within the acidic lysosome of tumor cells.PPI inhibits V-ATPase expression,leading to an increase in intracellular H+levels.H2S accelerates glucose consumption of tumor cells,producing more lactic acid and further inducing tumor acidosis.Tumor acidosis in turn accelerates the nanoplatform’s degradation,achieving higher tumor MRI.As the tumor acidosis degree correlates positively with tumor regression,real-time visualization of acidosis degree effectively predicts future therapeutics.Interestingly,tumor acidosis achieves efficient tumor metastasis suppression rather than increases it.Overall,this work presents a nanoplatform capable of visualizing tumor acidosis in real-time and precisely predicting future therapeutics.展开更多
Diabetes mellitus （DM） is one of the most common ＇metabolic disorders in the world~ in which more than90% are grouped to type 2 DM （T2DM）.1 T2DM is characterized by decreased insulin sensitivity and impaired insu...Diabetes mellitus （DM） is one of the most common ＇metabolic disorders in the world~ in which more than90% are grouped to type 2 DM （T2DM）.1 T2DM is characterized by decreased insulin sensitivity and impaired insulin secretion2 leading to hyperglycemia, and the serum glucose has been used as a golden standard for diabetes diagnosis. However, T2DM is a kind of disease involving defects of multiple organs, which cannot be distinguished through the measurement of the serum-glucose level. In addition, T2DM is a multiple-stage disease, which usually covers several decades from impaired plasma glucose to various complications. The serum-glucose level only reflects the consequence of multiole physiological disorders in the Riven stare.展开更多
Background:Bladder cancer is a common and highly heterogeneous malignant tumor with a relatively poor prognosis.Thus,personalized treatment strategies for bladder cancer are essential for improving patient outcomes.Ma...Background:Bladder cancer is a common and highly heterogeneous malignant tumor with a relatively poor prognosis.Thus,personalized treatment strategies for bladder cancer are essential for improving patient outcomes.Materials and methods:We developed an efficient 3-dimensional in vitro organoid culture system for bladder cancer organoids(BCOs),which maintains the homology with the original patient tumors and the heterogeneity between different individuals.In addition,we constructed chimeric antigen receptor(CAR)-T cells targeting B7H3 and evaluated the antitumor function of CAR-T cells by coculturing them with BCOs.Results:The BCOs closely resembled the characteristics of human tumors and were used to test individual sensitivity to platinum-based drugs and olaparib therapy.Coculture with CAR-T cells demonstrated specific antigen recognition and immune activation,indicating their potential in immunotherapy.Conclusions:Our study highlights the potential of BCOs to facilitate the development of personalized medicine for bladder cancer and improve the efficiency of drug discovery for bladder cancer therapy.展开更多
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.
基金supported by the National Natural Science Foundation of China(82372031)the Natural Science Foundation of Shandong(2022HWYQ-079,ZR2024QB135)+2 种基金the Taishan Scholar Foundation of Shandong Province(tsqn202408248)the Collaborative Academic Innovation Project of Shandong Cancer Hospital(TS002)the China Postdoctoral Science Foundation(2024M761874).
文摘Traditional antitumor strategies often require sufficient time to assess the effectiveness according to changes in tumor structure.Once ineffective,patients may miss the critical window for pursuing alternative treatment options.Herein,a manganese sulfide nanoplatform loaded with proton pump inhibitor(PPI)is developed.This nanoplatform is designed for visualizing tumor acidosis degree by magnetic resonance imaging(MRI),achieving real-time therapeutic efficacy precognition.The nanoplatform releases PPI,H2S,and Mn2+within the acidic lysosome of tumor cells.PPI inhibits V-ATPase expression,leading to an increase in intracellular H+levels.H2S accelerates glucose consumption of tumor cells,producing more lactic acid and further inducing tumor acidosis.Tumor acidosis in turn accelerates the nanoplatform’s degradation,achieving higher tumor MRI.As the tumor acidosis degree correlates positively with tumor regression,real-time visualization of acidosis degree effectively predicts future therapeutics.Interestingly,tumor acidosis achieves efficient tumor metastasis suppression rather than increases it.Overall,this work presents a nanoplatform capable of visualizing tumor acidosis in real-time and precisely predicting future therapeutics.
文摘Diabetes mellitus （DM） is one of the most common ＇metabolic disorders in the world~ in which more than90% are grouped to type 2 DM （T2DM）.1 T2DM is characterized by decreased insulin sensitivity and impaired insulin secretion2 leading to hyperglycemia, and the serum glucose has been used as a golden standard for diabetes diagnosis. However, T2DM is a kind of disease involving defects of multiple organs, which cannot be distinguished through the measurement of the serum-glucose level. In addition, T2DM is a multiple-stage disease, which usually covers several decades from impaired plasma glucose to various complications. The serum-glucose level only reflects the consequence of multiole physiological disorders in the Riven stare.
基金supported by the Key Research and Development Program of Shandong Province(No.2021CXGC01110)the Special Fund for Taishan Scholars Project(No.202211324)+1 种基金the Qingdao Science and Technology Program Project(No,20-3-4-38-nsh)the National Natural Science Foundation of China(No.81970743)..
文摘Background:Bladder cancer is a common and highly heterogeneous malignant tumor with a relatively poor prognosis.Thus,personalized treatment strategies for bladder cancer are essential for improving patient outcomes.Materials and methods:We developed an efficient 3-dimensional in vitro organoid culture system for bladder cancer organoids(BCOs),which maintains the homology with the original patient tumors and the heterogeneity between different individuals.In addition,we constructed chimeric antigen receptor(CAR)-T cells targeting B7H3 and evaluated the antitumor function of CAR-T cells by coculturing them with BCOs.Results:The BCOs closely resembled the characteristics of human tumors and were used to test individual sensitivity to platinum-based drugs and olaparib therapy.Coculture with CAR-T cells demonstrated specific antigen recognition and immune activation,indicating their potential in immunotherapy.Conclusions:Our study highlights the potential of BCOs to facilitate the development of personalized medicine for bladder cancer and improve the efficiency of drug discovery for bladder cancer therapy.
