Gastroesophageal cancers are leading causes of cancer death.Our attempts at adopting molecularly based treatment approaches have been slow and ineffective even though we begin to identify specific targetable gene muta...Gastroesophageal cancers are leading causes of cancer death.Our attempts at adopting molecularly based treatment approaches have been slow and ineffective even though we begin to identify specific targetable gene mutations and pathways.It is dear that we should no longer treat all gastroesophageal cancers as a homogeneous disease,which is what we do when we use nonspecific chemotherapy.However,we currently cannot monitor successful gene/pathway targeting,nor understand how/when tumors develop resistance,nor predict which patients will derive maximal benefit.To improve outcomes,we must precisely detail the heterogeneity of these tumors to then individualize cancer therapy as well as develop novel avenues to study and predict treatment effects in individual patients.To this end,patient-derived organoids,in which tumor cells from individual patients are grown in a Petri dish,are a new versatile system that allows for timely expandability,detailed molecular characterization,and genetic manipulation with the promise of enabling predictive assessment of treatment response.In this review,we will explore the development and basic techniques for organoid generation,and discuss the current and potential future applications of this exciting technology to study the basic science of carcinogenesis and to predict/guide cancer patient care in the clinics.展开更多
基金Support is provided by the NIDDK ROls(DK094989,DK105129,and DK110406)P30(DK052574)Alvin J.Siteman Cancer Center/Barnes Jewish Hospital Foundation Cancer Frontier Fund,NIH NCI(P30 CA091842 and U54 CA163060)The Barnard Trust,and DeNardo Education&Research Foundation grants to J.C.M.
文摘Gastroesophageal cancers are leading causes of cancer death.Our attempts at adopting molecularly based treatment approaches have been slow and ineffective even though we begin to identify specific targetable gene mutations and pathways.It is dear that we should no longer treat all gastroesophageal cancers as a homogeneous disease,which is what we do when we use nonspecific chemotherapy.However,we currently cannot monitor successful gene/pathway targeting,nor understand how/when tumors develop resistance,nor predict which patients will derive maximal benefit.To improve outcomes,we must precisely detail the heterogeneity of these tumors to then individualize cancer therapy as well as develop novel avenues to study and predict treatment effects in individual patients.To this end,patient-derived organoids,in which tumor cells from individual patients are grown in a Petri dish,are a new versatile system that allows for timely expandability,detailed molecular characterization,and genetic manipulation with the promise of enabling predictive assessment of treatment response.In this review,we will explore the development and basic techniques for organoid generation,and discuss the current and potential future applications of this exciting technology to study the basic science of carcinogenesis and to predict/guide cancer patient care in the clinics.
