Cold Spring Harbor perspectives in medicine最新文献_第10页

Advances in Making Cancer Mouse Models More Accessible and Informative through Non-Germline Genetic Engineering. 通过非血缘基因工程使癌症小鼠模型更易获得和更有信息量的进展。

IF 5.4 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-04-01 DOI: 10.1101/cshperspect.a041348

Katherine C Murphy, Marcus Ruscetti

{"title":"Advances in Making Cancer Mouse Models More Accessible and Informative through Non-Germline Genetic Engineering.","authors":"Katherine C Murphy, Marcus Ruscetti","doi":"10.1101/cshperspect.a041348","DOIUrl":"10.1101/cshperspect.a041348","url":null,"abstract":"Genetically engineered mouse models (GEMMs) allow for modeling of spontaneous tumorigenesis within its native microenvironment in mice and have provided invaluable insights into mechanisms of tumorigenesis and therapeutic strategies to treat human disease. However, as their generation requires germline manipulation and extensive animal breeding that is time-, labor-, and cost-intensive, traditional GEMMs are not accessible to most researchers, and fail to model the full breadth of cancer-associated genetic alterations and therapeutic targets. Recent advances in genome-editing technologies and their implementation in somatic tissues of mice have ushered in a new class of mouse models: non-germline GEMMs (nGEMMs). nGEMM approaches can be leveraged to generate somatic tumors de novo harboring virtually any individual or group of genetic alterations found in human cancer in a mouse through simple procedures that do not require breeding, greatly increasing the accessibility and speed and scale on which GEMMs can be produced. Here we describe the technologies and delivery systems used to create nGEMMs and highlight new biological insights derived from these models that have rapidly informed functional cancer genomics, precision medicine, and immune oncology.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10982712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9579397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Iron, Copper, and Selenium: Cancer's Thing for Redox Bling. 铁、铜和硒：癌症的红细胞闪烁。

IF 5.4 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-04-01 DOI: 10.1101/cshperspect.a041545

Erdem M Terzi, Richard Possemato

引用次数: 0

The Power and Promise of Patient-Derived Xenografts of Human Breast Cancer. 源于患者的人类乳腺癌异种移植物的力量和前景。

IF 5.4 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-04-01 DOI: 10.1101/cshperspect.a041329

Michael T Lewis, Carlos Caldas

{"title":"The Power and Promise of Patient-Derived Xenografts of Human Breast Cancer.","authors":"Michael T Lewis, Carlos Caldas","doi":"10.1101/cshperspect.a041329","DOIUrl":"10.1101/cshperspect.a041329","url":null,"abstract":"In 2016, a group of researchers engaged in the development of patient-derived xenografts (PDXs) of human breast cancer provided a comprehensive review of the state of the field. In that review, they summarized the clinical problem that PDXs might address, the technical approaches to their generation (including a discussion of host animals and transplant conditions tested), and presented transplantation success (take) rates across groups and across transplantation conditions. At the time, there were just over 500 unique PDX models created by these investigators representing all three clinically defined subtypes (ER+, HER2+, and TNBC). Today, many of these PDX resources have at least doubled in size, and several more PDX development groups now exist, such that there may be well upward of 1000 PDX models of human breast cancer in existence worldwide. They also presented a series of open questions for the field. Many of these questions have been addressed. However, several remain open, or only partially addressed. Herein, we revisit these questions, and recount the progress that has been made in a number of areas with respect to generation, characterization, and use of PDXs in translational research, and re-present questions that remain open. These open questions, and others, are now being addressed not only by individual investigators, but also large, well-funded consortia including the PDXNet program of the National Cancer Institute in the United States, and the EuroPDX Consortium, an organization of PDX developers across Europe. Finally, we discuss the new opportunities in PDX-based research.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10982691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138486882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

From the Inside Out: Exposing the Roles of Urea Cycle Enzymes in Tumors and Their Micro and Macro Environments. 由内而外：揭示尿素循环酶在肿瘤及其微观和宏观环境中的作用。

IF 5.4 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-04-01 DOI: 10.1101/cshperspect.a041538

Emma Hajaj, Sabina Pozzi, Ayelet Erez

{"title":"From the Inside Out: Exposing the Roles of Urea Cycle Enzymes in Tumors and Their Micro and Macro Environments.","authors":"Emma Hajaj, Sabina Pozzi, Ayelet Erez","doi":"10.1101/cshperspect.a041538","DOIUrl":"10.1101/cshperspect.a041538","url":null,"abstract":"Catabolic pathways change in anabolic diseases such as cancer to maintain metabolic homeostasis. The liver urea cycle (UC) is the main catabolic pathway for disposing excess nitrogen. Outside the liver, the UC enzymes are differentially expressed based on each tissue's needs for UC intermediates. In tumors, there are changes in the expression of UC enzymes selected for promoting tumorigenesis by increasing the availability of essential UC substrates and products. Consequently, there are compensatory changes in the expression of UC enzymes in the cells that compose the tumor microenvironment. Moreover, extrahepatic tumors induce changes in the expression of the liver UC, which contribute to the systemic manifestations of cancer, such as weight loss. Here, we review the multilayer changes in the expression of UC enzymes throughout carcinogenesis. Understanding the changes in UC expression in the tumor and its micro and macro environment can help identify biomarkers for early cancer diagnosis and vulnerabilities that can be targeted for therapy.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10982720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10267773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pig Models in Retinal Research and Retinal Disease. 视网膜研究和视网膜疾病中的猪模型。

IF 5.4 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-04-01 DOI: 10.1101/cshperspect.a041296

Maureen A McCall

{"title":"Pig Models in Retinal Research and Retinal Disease.","authors":"Maureen A McCall","doi":"10.1101/cshperspect.a041296","DOIUrl":"10.1101/cshperspect.a041296","url":null,"abstract":"The pig has been used as a large animal model in biomedical research for many years and its use continues to increase because induced mutations phenocopy several inherited human diseases. In addition, they are continuous breeders, can be propagated by artificial insemination, have large litter sizes (on the order of mice), and can be genetically manipulated using all of the techniques that are currently available in mice. The pioneering work of Petters and colleagues set the stage for the use of the pig as a model of inherited retinal disease. In the last 10 years, the pig has become a model of choice where specific disease-causing mutations that are not phenocopied in rodents need to be studied and therapeutic approaches explored. The pig is not only used for retinal eye disease but also for the study of the cornea and lens. This review attempts to show how broad the use of the pig has become and how it has contributed to the assessment of treatments for eye disease. In the last 10 years, there have been several reviews that included the use of the pig in biomedical research (see body of the review) that included information about retinal disease. None directly discuss the use of the pig as an animal model for retinal diseases, including inherited diseases, where a single genetic mutation has been identified or for multifactorial diseases such as glaucoma and diabetic retinopathy. Although the pig is used to explore diseases of the cornea and lens, this review focuses on how and why the pig, as a large animal model, is useful for research in neural retinal disease and its treatment.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10982707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10316574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pediatric Cancer Drug Development: Leveraging Insights in Cancer Biology and the Evolving Regulatory Landscape to Address Challenges and Guide Further Progress. 儿科癌症药物开发：利用对癌症生物学和不断变化的监管环境的深入了解，应对挑战并指导进一步的进展。

IF 5.4 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-04-01 DOI: 10.1101/cshperspect.a041656

Rosane Charlab, Ruby Leong, Stacy S Shord, Gregory H Reaman

{"title":"Pediatric Cancer Drug Development: Leveraging Insights in Cancer Biology and the Evolving Regulatory Landscape to Address Challenges and Guide Further Progress.","authors":"Rosane Charlab, Ruby Leong, Stacy S Shord, Gregory H Reaman","doi":"10.1101/cshperspect.a041656","DOIUrl":"10.1101/cshperspect.a041656","url":null,"abstract":"The discovery and development of anticancer drugs for pediatric patients have historically languished when compared to both past and recent activity in drug development for adult patients, notably the dramatic spike of targeted and immune-oncology therapies. The reasons for this difference are multifactorial. Recent changes in the regulatory landscape surrounding pediatric cancer drug development and the understanding that some pediatric cancers are driven by genetic perturbations that also drive disparate adult cancers afford new opportunities. The unique cancer-initiating events and dependencies of many pediatric cancers, however, require additional pediatric-specific strategies. Research efforts to unravel the underlying biology of pediatric cancers, innovative clinical trial designs, model-informed drug development, extrapolation from adult data, addressing the unique considerations in pediatric patients, and use of pediatric appropriate formulations, should all be considered for efficient development and dosage optimization of anticancer drugs for pediatric patients.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10982696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140101225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Acute Promyelocytic Leukemia, Retinoic Acid, and Arsenic: A Tale of Dualities 急性早幼粒细胞白血病、维甲酸和砷：双重性的故事

IF 5.4 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-03-19 DOI: 10.1101/cshperspect.a041582

Domitille Rérolle, Hsin-Chieh Wu, Hugues de Thé

{"title":"Acute Promyelocytic Leukemia, Retinoic Acid, and Arsenic: A Tale of Dualities","authors":"Domitille Rérolle, Hsin-Chieh Wu, Hugues de Thé","doi":"10.1101/cshperspect.a041582","DOIUrl":"https://doi.org/10.1101/cshperspect.a041582","url":null,"abstract":"Acute promyelocytic leukemia (APL) is driven by the promyelocytic leukemia (PML)/retinoic acid receptor α (RARA) fusion oncoprotein. Over the years, it has emerged as a model system to understand how this simple (and sometimes sole) genetic alteration can transform hematopoietic progenitors through the acquisition of dominant-negative properties toward both transcriptional control by nuclear receptors and PML-mediated senescence. The fortuitous identification of two drugs, arsenic trioxide (ATO) and all-trans-retinoic acid (ATRA), that respectively bind PML and RARA to initiate PML/RARA degradation, has allowed an unprecedented dissection of the cellular and molecular mechanisms involved in patients’ cure by the ATO/ATRA combination. This analysis has unraveled the dual and complementary roles of RARA and PML in both APL initiation and cure by the ATRA/ATO combination. We discuss how some of the features unraveled by APL studies may be more broadly applicable to some other forms of leukemia. In particular, the functional synergy between drugs that promote differentiation and those that initiate apoptosis/senescence to impede self-renewal could pave the way to novel curative combinations.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":"20 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140168248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Addressing Biological Questions with Preclinical Cancer Imaging 利用临床前癌症成像解决生物学问题

IF 5.4 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-03-19 DOI: 10.1101/cshperspect.a041378

Chris B. Damoci, Joseph R. Merrill, Yanping Sun, Scott K. Lyons, Kenneth P. Olive

引用次数: 0

Knowledge-Based Therapeutics for Tricarboxylic Acid (TCA) Cycle-Deficient Cancers 基于知识的三羧酸 (TCA) 循环缺陷癌症疗法

IF 5.4 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-03-19 DOI: 10.1101/cshperspect.a041536

Daniel Peled, Ruth Casey, Eyal Gottlieb

引用次数: 0

Tracing the Diverse Paths of One-Carbon Metabolism in Cancer and Beyond 追踪一碳代谢在癌症及其他疾病中的不同路径

IF 5.4 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-03-19 DOI: 10.1101/cshperspect.a041533

Esther W. Lim, Christian M. Metallo

引用次数: 0