Cold Spring Harbor perspectives in medicine This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

[PERSPECTIVES] Pediatric Cancer Drug Development: Leveraging Insights in Cancer Biology and the Evolving Regulatory Landscape to Address Challenges and Guide Further Progress
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...
Source: Cold Spring Harbor perspectives in medicine - April 1, 2024 Category: Research Authors: Charlab, R., Leong, R., Shord, S. S., Reaman, G. H. Tags: Developmental Oncology: Principles and Therapy of Cancers of Children and Young Adults PERSPECTIVES Source Type: research

[PERSPECTIVES] Iron, Copper, and Selenium: Cancer's Thing for Redox Bling
Cells require micronutrients for numerous basic functions. Among these, iron, copper, and selenium are particularly critical for redox metabolism, and their importance is heightened during oncogene-driven perturbations in cancer. In this review, which particularly focuses on iron, we describe how these micronutrients are carefully chaperoned about the body and made available to tissues, a process that is designed to limit the toxicity of free iron and copper or by-products of selenium metabolism. We delineate perturbations in iron metabolism and iron-dependent proteins that are observed in cancer, and describe the current ...
Source: Cold Spring Harbor perspectives in medicine - April 1, 2024 Category: Research Authors: Terzi, E. M., Possemato, R. Tags: Cancer Metabolism: Historical Landmarks, New Concepts, and Opportunities PERSPECTIVES Source Type: research

[PERSPECTIVES] From the Inside Out: Exposing the Roles of Urea Cycle Enzymes in Tumors and Their Micro and Macro Environments
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 i...
Source: Cold Spring Harbor perspectives in medicine - April 1, 2024 Category: Research Authors: Hajaj, E., Pozzi, S., Erez, A. Tags: Cancer Metabolism: Historical Landmarks, New Concepts, and Opportunities PERSPECTIVES Source Type: research

[PERSPECTIVES] Advances in Making Cancer Mouse Models More Accessible and Informative through Non-Germline Genetic Engineering
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 somati...
Source: Cold Spring Harbor perspectives in medicine - April 1, 2024 Category: Research Authors: Murphy, K. C., Ruscetti, M. Tags: Modeling Cancer in Mice PERSPECTIVES Source Type: research

[PERSPECTIVES] The Power and Promise of Patient-Derived Xenografts of Human Breast Cancer
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+,...
Source: Cold Spring Harbor perspectives in medicine - April 1, 2024 Category: Research Authors: Lewis, M. T., Caldas, C. Tags: Breast Cancer: From Fundamental Biology to Therapeutic Strategies PERSPECTIVES Source Type: research

[PERSPECTIVES] Pig Models in Retinal Research and Retinal Disease
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 diseas...
Source: Cold Spring Harbor perspectives in medicine - April 1, 2024 Category: Research Authors: McCall, M. A. Tags: Retinal Disorders: Genetic Approaches to Diagnosis and Treatment PERSPECTIVES Source Type: research

[PERSPECTIVES] Mutations, Bottlenecks, and Clonal Sweeps: How Environmental Carcinogens and Genomic Changes Shape Clonal Evolution during Tumor Progression
The transition from a single, initiated cell to a full-blown malignant tumor involves significant genomic evolution. Exposure to carcinogens—whether directly mutagenic or not—can drive progression toward malignancy, as can stochastic acquisition of cancer-promoting genetic events. Mouse models using both carcinogens and germline genetic manipulations have enabled precise inquiry into the evolutionary dynamics that take place as a tumor progresses from benign to malignant to metastatic stages. Tumor progression is characterized by changes in somatic point mutations and copy-number alterations, even though any si...
Source: Cold Spring Harbor perspectives in medicine - March 1, 2024 Category: Research Authors: Reeves, M. Q., Balmain, A. Tags: Modeling Cancer in Mice PERSPECTIVES Source Type: research

[PERSPECTIVES] Advances in Immunocompetent Mouse and Rat Models
Rodent models of breast cancer have played critical roles in our understanding of breast cancer development and progression as well as preclinical testing of cancer prevention and therapeutics. In this article, we first review the values and challenges of conventional genetically engineered mouse (GEM) models and newer iterations of these models, especially those with inducible or conditional regulation of oncogenes and tumor suppressors. Then, we discuss nongermline (somatic) GEM models of breast cancer with temporospatial control, made possible by intraductal injection of viral vectors to deliver oncogenes or to manipula...
Source: Cold Spring Harbor perspectives in medicine - March 1, 2024 Category: Research Authors: Bu, W., Li, Y. Tags: Breast Cancer: From Fundamental Biology to Therapeutic Strategies PERSPECTIVES Source Type: research

[PERSPECTIVES] Considerations for Developing an Autologous Induced Pluripotent Stem Cell (iPSC)-Derived Retinal Pigment Epithelium (RPE) Replacement Therapy
Cell-replacement therapies are a new class of treatments, which include induced pluripotent stem cell (iPSC)-derived tissues that aim to replace degenerated cells. iPSCs can potentially be used to generate any cell type of the body, making them a powerful tool for treating degenerative diseases. Cell replacement for retinal degenerative diseases is at the forefront of cell therapies, given the accessibility of the eye for surgical procedures and a huge unmet medical need for retinal degenerative diseases with no current treatment options. Clinical trials are ongoing in different parts of the world using stem cell–der...
Source: Cold Spring Harbor perspectives in medicine - March 1, 2024 Category: Research Authors: Bose, D., Ortolan, D., Farnoodian, M., Sharma, R., Bharti, K. Tags: Retinal Disorders: Genetic Approaches to Diagnosis and Treatment PERSPECTIVES Source Type: research

[PERSPECTIVES] Toward Retinal Organoids in High-Throughput
Human retinal organoids recapitulate the cellular diversity, arrangement, gene expression, and functional aspects of the human retina. Protocols to generate human retinal organoids from pluripotent stem cells are typically labor intensive, include many manual handling steps, and the organoids need to be maintained for several months until they mature. To generate large numbers of human retinal organoids for therapy development and screening purposes, scaling up retinal organoid production, maintenance, and analysis is of utmost importance. In this review, we discuss strategies to increase the number of high-quality retinal...
Source: Cold Spring Harbor perspectives in medicine - March 1, 2024 Category: Research Authors: Spirig, S. E., Renner, M. Tags: Retinal Disorders: Genetic Approaches to Diagnosis and Treatment PERSPECTIVES Source Type: research

[PERSPECTIVES] Mitochondrial Targeted Interventions for Aging
Changes in mitochondrial function play a critical role in the basic biology of aging and age-related disease. Mitochondria are typically thought of in the context of ATP production and oxidant production. However, it is clear that the mitochondria sit at a nexus of cell signaling where they affect metabolite, redox, and energy status, which influence many factors that contribute to the biology of aging, including stress responses, proteostasis, epigenetics, and inflammation. This has led to growing interest in identifying mitochondrial targeted interventions to delay or reverse age-related decline in function and promote h...
Source: Cold Spring Harbor perspectives in medicine - March 1, 2024 Category: Research Authors: Liu, S. Z., Chiao, Y. A., Rabinovitch, P. S., Marcinek, D. J. Tags: Aging PERSPECTIVES Source Type: research

[PERSPECTIVES] Cancer Metabolism under Limiting Oxygen Conditions
Molecular oxygen (O2) is essential for cellular bioenergetics and numerous biochemical reactions necessary for life. Solid tumors outgrow the native blood supply and diffusion limits of O2, and therefore must engage hypoxia response pathways that evolved to withstand acute periods of low O2. Hypoxia activates coordinated gene expression programs, primarily through hypoxia inducible factors (HIFs), to support survival. Many of these changes involve metabolic rewiring such as increasing glycolysis to support ATP generation while suppressing mitochondrial metabolism. Since low O2 is often coupled with nutrient stress in the t...
Source: Cold Spring Harbor perspectives in medicine - February 1, 2024 Category: Research Authors: Kim, L. C., Lesner, N. P., Simon, M. C. Tags: Cancer Metabolism: Historical Landmarks, New Concepts, and Opportunities PERSPECTIVES Source Type: research

[PERSPECTIVES] Breast Cancer Immunity: It is TIME for the Next Chapter
Our ability to interrogate the tumor immune microenvironment (TIME) at an ever-increasing granularity has uncovered critical determinants of disease progression. Not only do we now have a better understanding of the immune response in breast cancer, but it is becoming possible to leverage key mechanisms to effectively combat this disease. Almost every component of the immune system plays a role in enabling or inhibiting breast tumor growth. Building on early seminal work showing the involvement of T cells and macrophages in controlling breast cancer progression and metastasis, single-cell genomics and spatial proteomics ap...
Source: Cold Spring Harbor perspectives in medicine - February 1, 2024 Category: Research Authors: Quail, D. F., Park, M., Welm, A. L., Ekiz, H. A. Tags: Breast Cancer: From Fundamental Biology to Therapeutic Strategies PERSPECTIVES Source Type: research

[PERSPECTIVES] Canine and Feline Models of Inherited Retinal Diseases
Naturally occurring inherited retinal diseases (IRDs) in cats and dogs provide a rich source of potential models for human IRDs. In many cases, the phenotypes between the species with mutations of the homologous genes are very similar. Both cats and dogs have a high-acuity retinal region, the area centralis, an equivalent to the human macula, with tightly packed photoreceptors and higher cone density. This and the similarity in globe size to that of humans means these large animal models provide information not obtainable from rodent models. The established cat and dog models include those for Leber congenital amaurosis, r...
Source: Cold Spring Harbor perspectives in medicine - February 1, 2024 Category: Research Authors: Petersen-Jones, S. M., Komaromy, A. M. Tags: Retinal Disorders: Genetic Approaches to Diagnosis and Treatment PERSPECTIVES Source Type: research

[PERSPECTIVES] Comparison of Worldwide Disease Prevalence and Genetic Prevalence of Inherited Retinal Diseases and Variant Interpretation Considerations
One of the considerations in planning the development of novel therapeutic modalities is disease prevalence that is usually defined by studying large national/regional populations. Such studies are rare and might suffer from inaccuracies and challenging clinical characterization in heterogeneous diseases, such as inherited retinal diseases (IRDs). Here we collected reported disease prevalence information on various IRDs in different populations. The most common IRD, retinitis pigmentosa, has an average disease prevalence of ~1:4500 individuals, Stargardt disease ~1:17,000, Usher syndrome ~1:25,000, Leber congenital amauros...
Source: Cold Spring Harbor perspectives in medicine - February 1, 2024 Category: Research Authors: Hanany, M., Shalom, S., Ben-Yosef, T., Sharon, D. Tags: Retinal Disorders: Genetic Approaches to Diagnosis and Treatment PERSPECTIVES Source Type: research