Twenty-five years ago,Nembrot and colleagues reported amplification of the estrogen receptor alpha gene(ESR1) in breast cancer,initiating a broad and still ongoing scientific debate on the prevalence and clinical sign...Twenty-five years ago,Nembrot and colleagues reported amplification of the estrogen receptor alpha gene(ESR1) in breast cancer,initiating a broad and still ongoing scientific debate on the prevalence and clinical significance of this genetic aberration,which affects one of the most important genes in breast cancer.Since then,a multitude of studies on this topic has been published,covering a wide range of divergent results and arguments.The reported prevalence of this alteration in breast cancer ranges from 0% to 75%,suggesting that ESR1 copy number analysis is hampered by technical and interpreter issues.To date,two major issues related to ESR1 amplification remain to be conclusively addressed:(1) The extent to which abundant amounts of messenger RNA can mimic amplification in standard fluorescence in situ hybridization assays in the analysis of strongly expressed genes like ESR1,and(2) the clinical relevance of ESR1 amplification:Such relevance is strongly disputed,with data showing predictive value for response as well as for resistance of the cancer to anti-estrogen therapies,or for subsequent development of cancers in the case of precursor lesions that display amplification of ESR1.This review provides a comprehensive summary of the various views on ESR1 amplification,and highlights explanations for the contradictions and conflicting data that could inform future ESR1 research.展开更多
The tumor microenvironment represents a dynamic and multifaceted milieu characterized by the complex interactions of diverse cellular and non-cellular constituents.1,2 These constituents include tumor cells,microorgan...The tumor microenvironment represents a dynamic and multifaceted milieu characterized by the complex interactions of diverse cellular and non-cellular constituents.1,2 These constituents include tumor cells,microorganisms,immune and other stromal cells,and extracellular matrices.The orchestration of these components intricately contributes to tumor evolution and shapes responses to cancer treatment(Figure 1).A better understanding of the tumor microenvironment is critical to elucidate the etiology of cancer and develop more efficient therapeutic strategies.展开更多
文摘Twenty-five years ago,Nembrot and colleagues reported amplification of the estrogen receptor alpha gene(ESR1) in breast cancer,initiating a broad and still ongoing scientific debate on the prevalence and clinical significance of this genetic aberration,which affects one of the most important genes in breast cancer.Since then,a multitude of studies on this topic has been published,covering a wide range of divergent results and arguments.The reported prevalence of this alteration in breast cancer ranges from 0% to 75%,suggesting that ESR1 copy number analysis is hampered by technical and interpreter issues.To date,two major issues related to ESR1 amplification remain to be conclusively addressed:(1) The extent to which abundant amounts of messenger RNA can mimic amplification in standard fluorescence in situ hybridization assays in the analysis of strongly expressed genes like ESR1,and(2) the clinical relevance of ESR1 amplification:Such relevance is strongly disputed,with data showing predictive value for response as well as for resistance of the cancer to anti-estrogen therapies,or for subsequent development of cancers in the case of precursor lesions that display amplification of ESR1.This review provides a comprehensive summary of the various views on ESR1 amplification,and highlights explanations for the contradictions and conflicting data that could inform future ESR1 research.
基金supported in part by the Cancer Research UK Cancer Grand Challenge Award(6340201/A27140)NIH grant(R01 CA248857)+1 种基金T.U.was supported by NIH grant R50 CA27412a Brigham and Women’s Hospital Faculty Career Development Award,an Investigator Initiated Grant from the American Institute for Cancer Research(AICR),a Prevent Cancer Foundation Fellowship,and the Harvey V.Fineberg Fellowship in Cancer Prevention from Harvard T.H.Chan School of Public Health.S.U.was supported by a grant from the Uehara Memorial Foundation.S.O.is an American Cancer Society Clinical Research Professor。
文摘The tumor microenvironment represents a dynamic and multifaceted milieu characterized by the complex interactions of diverse cellular and non-cellular constituents.1,2 These constituents include tumor cells,microorganisms,immune and other stromal cells,and extracellular matrices.The orchestration of these components intricately contributes to tumor evolution and shapes responses to cancer treatment(Figure 1).A better understanding of the tumor microenvironment is critical to elucidate the etiology of cancer and develop more efficient therapeutic strategies.
