Pub Date : 2025-03-17DOI: 10.1101/cshperspect.a041847
Alex Kentsis, Alejandro Gutierrez
Children and young adults are affected by a number of different cancers. These are developmental in origin and arise, in particular, in susceptible cell types. Recent advances have led to significant progress in our understanding of the underlying causes and the pathogenetic mechanisms involved. This is informing design of therapeutic approaches that offer new hope for patients.
{"title":"Developmental Oncology: Principles and Therapy of Cancers of Children and Young Adults.","authors":"Alex Kentsis, Alejandro Gutierrez","doi":"10.1101/cshperspect.a041847","DOIUrl":"https://doi.org/10.1101/cshperspect.a041847","url":null,"abstract":"<p><p>Children and young adults are affected by a number of different cancers. These are developmental in origin and arise, in particular, in susceptible cell types. Recent advances have led to significant progress in our understanding of the underlying causes and the pathogenetic mechanisms involved. This is informing design of therapeutic approaches that offer new hope for patients.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647594","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}
Pub Date : 2025-03-17DOI: 10.1101/cshperspect.a041630
Arturo Casadevall
The fungal kingdom includes a large set of species with pathogenic potential for humans, plants, and wildlife. Whereas threats from the fungal kingdom to agriculture are appreciated, the potential of fungi to threaten humans, animals, ecosystems, and infrastructure is often unappreciated. Fungal disease and mold damage often follow natural disasters. The threats from the fungal kingdom are amplified by the relative paucity of countermeasures, which includes few antifungal drugs and fungicides and an increasing prevalence of resistance to both. Anthropomorphic climate change resulting in global warming is expected to increase the likelihood and potential number of threats from the fungal kingdom. Preparation against fungal threats requires continued investments in basic research to understand the unique aspects of fungal metabolism, development of vaccines, investment in new drugs and fungicides, and a careful mapping of the natural world to identify the existing taxonomic diversity and their potential for harm.
{"title":"Threats from the Fungal Kingdom.","authors":"Arturo Casadevall","doi":"10.1101/cshperspect.a041630","DOIUrl":"https://doi.org/10.1101/cshperspect.a041630","url":null,"abstract":"<p><p>The fungal kingdom includes a large set of species with pathogenic potential for humans, plants, and wildlife. Whereas threats from the fungal kingdom to agriculture are appreciated, the potential of fungi to threaten humans, animals, ecosystems, and infrastructure is often unappreciated. Fungal disease and mold damage often follow natural disasters. The threats from the fungal kingdom are amplified by the relative paucity of countermeasures, which includes few antifungal drugs and fungicides and an increasing prevalence of resistance to both. Anthropomorphic climate change resulting in global warming is expected to increase the likelihood and potential number of threats from the fungal kingdom. Preparation against fungal threats requires continued investments in basic research to understand the unique aspects of fungal metabolism, development of vaccines, investment in new drugs and fungicides, and a careful mapping of the natural world to identify the existing taxonomic diversity and their potential for harm.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647600","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}
Pub Date : 2025-03-17DOI: 10.1101/cshperspect.a041609
Julia Segal, James Cronk, Brendan Ball, Greta Forbes, Kailey Jackett, Kathy Li, Alondra Martinez Osorno, Emily San Andres Montalvan, Alice Browne, Jessica Lake, Rosandra N Kaplan
The tumor microenvironment (TME) is comprised of both cellular and stromal elements and plays an essential role in the growth, survival, and dissemination of malignancies. The TME is an organized program that develops with a growing tumor, using many processes involved in normal tissue development. In multiple solid tumors, developmental pathways are used to recruit immunosuppressive cells, including immunosuppressive monocytes and neutrophils, tumor-associated macrophages, and regulatory T cells to block the antitumor immune response. In addition, stromal cells sustain tumor growth via trophic support, angiogenesis, repair mechanisms, and associated immunosuppression, driven, at least in part, by canonical developmental signaling pathways. The microenvironmental ecosystem shapes tumor progression from its earliest inception by modulating important programs that dictate tumor behavior, necessitating further consideration when studying the developmental origins of malignancy. Here, we review the role of developmental pathways in the formation and modulation of the TME in pediatric and adult solid tumors, including Wnt, Notch, Hippo, Hedgehog, TGF-β, BMP, SOX, and OCT.
肿瘤微环境(TME)由细胞和基质两部分组成,在恶性肿瘤的生长、存活和扩散过程中起着至关重要的作用。肿瘤微环境是一个有组织的程序,它随着肿瘤的生长而发展,并利用正常组织发育的许多过程。在多种实体瘤中,发育途径被用来招募免疫抑制细胞,包括免疫抑制单核细胞和中性粒细胞、肿瘤相关巨噬细胞和调节性 T 细胞,以阻断抗肿瘤免疫反应。此外,基质细胞通过营养支持、血管生成、修复机制和相关的免疫抑制来维持肿瘤生长,至少部分是由典型的发育信号通路驱动的。微环境生态系统通过调节决定肿瘤行为的重要程序,从一开始就影响着肿瘤的进展,因此在研究恶性肿瘤的发育起源时有必要进一步加以考虑。在此,我们回顾了发育通路在儿童和成人实体瘤中形成和调节TME中的作用,包括Wnt、Notch、Hippo、Hedgehog、TGF-β、BMP、SOX和OCT。
{"title":"Parallels in Canonical Developmental Signaling Pathways between Normal Development and the Tumor Microenvironment.","authors":"Julia Segal, James Cronk, Brendan Ball, Greta Forbes, Kailey Jackett, Kathy Li, Alondra Martinez Osorno, Emily San Andres Montalvan, Alice Browne, Jessica Lake, Rosandra N Kaplan","doi":"10.1101/cshperspect.a041609","DOIUrl":"https://doi.org/10.1101/cshperspect.a041609","url":null,"abstract":"<p><p>The tumor microenvironment (TME) is comprised of both cellular and stromal elements and plays an essential role in the growth, survival, and dissemination of malignancies. The TME is an organized program that develops with a growing tumor, using many processes involved in normal tissue development. In multiple solid tumors, developmental pathways are used to recruit immunosuppressive cells, including immunosuppressive monocytes and neutrophils, tumor-associated macrophages, and regulatory T cells to block the antitumor immune response. In addition, stromal cells sustain tumor growth via trophic support, angiogenesis, repair mechanisms, and associated immunosuppression, driven, at least in part, by canonical developmental signaling pathways. The microenvironmental ecosystem shapes tumor progression from its earliest inception by modulating important programs that dictate tumor behavior, necessitating further consideration when studying the developmental origins of malignancy. Here, we review the role of developmental pathways in the formation and modulation of the TME in pediatric and adult solid tumors, including Wnt, Notch, Hippo, Hedgehog, TGF-β, BMP, SOX, and OCT.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647598","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}
Pub Date : 2025-03-17DOI: 10.1101/cshperspect.a041841
Yoshikazu Nakano, Martin Niethammer, David Eidelberg
Functional neuroimaging techniques are increasingly being used to advance the diagnosis and management of Parkinson's disease (PD). Methods such as [18F]-fluorodeoxyglucose positron emission tomography (FDG PET), resting-state functional magnetic resonance imaging (rs-fMRI), arterial spin labeling (ASL) MRI, and single-photon emission computed tomography (SPECT) enable the identification of disease-specific patterns like the PD-related pattern (PDRP) and PD cognition-related pattern (PDCP), which correlate with motor and cognitive symptoms. Network analysis using graph theory further elucidates the alterations in brain connectivity associated with PD, providing insights into disease progression and response to treatment. Moreover, these neuroimaging patterns assist in distinguishing PD from atypical parkinsonian syndromes, enhancing diagnostic accuracy. Understanding the impact of genetic variants like LRRK2 and GBA1 on functional connectivity highlights the potential for precision medicine in PD. As neuroimaging technologies evolve, their integration into clinical practice will be pivotal in the personalized management of PD, offering improved diagnostic precision and targeted therapeutic interventions.
{"title":"Imaging of Disease-Related Networks in Parkinson's Disease.","authors":"Yoshikazu Nakano, Martin Niethammer, David Eidelberg","doi":"10.1101/cshperspect.a041841","DOIUrl":"https://doi.org/10.1101/cshperspect.a041841","url":null,"abstract":"<p><p>Functional neuroimaging techniques are increasingly being used to advance the diagnosis and management of Parkinson's disease (PD). Methods such as [<sup>18</sup>F]-fluorodeoxyglucose positron emission tomography (FDG PET), resting-state functional magnetic resonance imaging (rs-fMRI), arterial spin labeling (ASL) MRI, and single-photon emission computed tomography (SPECT) enable the identification of disease-specific patterns like the PD-related pattern (PDRP) and PD cognition-related pattern (PDCP), which correlate with motor and cognitive symptoms. Network analysis using graph theory further elucidates the alterations in brain connectivity associated with PD, providing insights into disease progression and response to treatment. Moreover, these neuroimaging patterns assist in distinguishing PD from atypical parkinsonian syndromes, enhancing diagnostic accuracy. Understanding the impact of genetic variants like <i>LRRK2</i> and <i>GBA1</i> on functional connectivity highlights the potential for precision medicine in PD. As neuroimaging technologies evolve, their integration into clinical practice will be pivotal in the personalized management of PD, offering improved diagnostic precision and targeted therapeutic interventions.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647596","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}
Pub Date : 2025-03-03DOI: 10.1101/cshperspect.a041682
Marcus Bosenberg
The recent rise in effective immuno-oncology therapies has increased demand for experimental approaches to model anticancer immunity. A variety of mouse models have been developed and used to study cancer immunology. These include mutagen-induced, genetically engineered, syngeneic, and other models of cancer immunology. These models each have the potential to define mechanistic aspects of anticancer immune responses, identify potential therapeutic targets, and serve as preclinical models for further therapeutic development. Specific benefits and liabilities are characteristic of particular cancer immunology modeling approaches. The optimal choice and utilization of models depends on the cancer immunology scientific question being addressed and can serve to increase mechanistic understanding and development of human immuno-oncology therapies.
{"title":"Advances in Studying Cancer Immunology in Mice.","authors":"Marcus Bosenberg","doi":"10.1101/cshperspect.a041682","DOIUrl":"10.1101/cshperspect.a041682","url":null,"abstract":"<p><p>The recent rise in effective immuno-oncology therapies has increased demand for experimental approaches to model anticancer immunity. A variety of mouse models have been developed and used to study cancer immunology. These include mutagen-induced, genetically engineered, syngeneic, and other models of cancer immunology. These models each have the potential to define mechanistic aspects of anticancer immune responses, identify potential therapeutic targets, and serve as preclinical models for further therapeutic development. Specific benefits and liabilities are characteristic of particular cancer immunology modeling approaches. The optimal choice and utilization of models depends on the cancer immunology scientific question being addressed and can serve to increase mechanistic understanding and development of human immuno-oncology therapies.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141075768","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}
Pub Date : 2025-03-03DOI: 10.1101/cshperspect.a041643
Kim Tieu, Said S Salehe, Harry J Brown
The debilitating motor symptoms of Parkinson's disease (PD) result primarily from the degenerative nigrostriatal dopaminergic pathway. To elucidate pathogenic mechanisms and evaluate therapeutic strategies for PD, numerous animal models have been developed. Understanding the strengths and limitations of these models can significantly impact the choice of model, experimental design, and data interpretation. Herein, we systematically review the literature over the past decade. Some models no longer serve the purpose of PD models. The primary objectives of this review are: First, to assist new investigators in navigating through available animal models and making appropriate selections based on the objective of the study. Emphasis will be placed on common toxin-induced murine models. And second, to provide an overview of basic technical requirements for assessing the nigrostriatal pathway's pathology, structure, and function.
{"title":"Toxin-Induced Animal Models of Parkinson's Disease.","authors":"Kim Tieu, Said S Salehe, Harry J Brown","doi":"10.1101/cshperspect.a041643","DOIUrl":"10.1101/cshperspect.a041643","url":null,"abstract":"<p><p>The debilitating motor symptoms of Parkinson's disease (PD) result primarily from the degenerative nigrostriatal dopaminergic pathway. To elucidate pathogenic mechanisms and evaluate therapeutic strategies for PD, numerous animal models have been developed. Understanding the strengths and limitations of these models can significantly impact the choice of model, experimental design, and data interpretation. Herein, we systematically review the literature over the past decade. Some models no longer serve the purpose of PD models. The primary objectives of this review are: First, to assist new investigators in navigating through available animal models and making appropriate selections based on the objective of the study. Emphasis will be placed on common toxin-induced murine models. And second, to provide an overview of basic technical requirements for assessing the nigrostriatal pathway's pathology, structure, and function.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476108","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}
Pub Date : 2025-03-03DOI: 10.1101/cshperspect.a041779
Diane R Bielenberg, Patricia A D'Amore
During development, the first blood vessels are formed by the de novo assembly of angioblasts, endothelial cell precursors, in a process called vasculogenesis. All subsequent sprouting of blood vessels from pre-existing vessels is termed angiogenesis and is a process that continues throughout our lifespan during physiological processes such as wound healing as well as in number of pathological conditions, such as tumor growth and age-related macular degeneration. The circulatory system pumps blood from the heart out to the organs through arteries and deliveries oxygen and nutrients via capillaries to tissues and cells and returns carbon dioxide and waste products back through veins. Each organ varies in its blood vessel patterning, reflecting specialization to accomplish diverse functions including vascular permeability, filtration, immune trafficking, and hormone regulation. Approximately 90% of the fluid extravasated into the interstitium is recycled back to the circulatory system via the unidirectional lymphatic system. Lymphatic capillaries drain fluid, proteins, and cells from tissues and transport this lymph fluid through collecting lymphatic ducts toward lymph nodes. Eventually lymphatic fluid from the right and left lymphatic ducts joins the subclavian veins and recirculates throughout the circulatory system. These two intricate vascular systems, working in cooperation, help to maintain essential bodily functions such as fluid dynamics, tissue homeostasis, blood pressure, metabolism, and immunity. However, dysfunction of these systems is associated with a host of pathological conditions, including cardiovascular diseases, obesity, retinopathy, hypoxia, necrosis, and vascular malformations.
{"title":"Angiogenesis: Biology and Pathology, Second Edition.","authors":"Diane R Bielenberg, Patricia A D'Amore","doi":"10.1101/cshperspect.a041779","DOIUrl":"10.1101/cshperspect.a041779","url":null,"abstract":"<p><p>During development, the first blood vessels are formed by the de novo assembly of angioblasts, endothelial cell precursors, in a process called vasculogenesis. All subsequent sprouting of blood vessels from pre-existing vessels is termed angiogenesis and is a process that continues throughout our lifespan during physiological processes such as wound healing as well as in number of pathological conditions, such as tumor growth and age-related macular degeneration. The circulatory system pumps blood from the heart out to the organs through arteries and deliveries oxygen and nutrients via capillaries to tissues and cells and returns carbon dioxide and waste products back through veins. Each organ varies in its blood vessel patterning, reflecting specialization to accomplish diverse functions including vascular permeability, filtration, immune trafficking, and hormone regulation. Approximately 90% of the fluid extravasated into the interstitium is recycled back to the circulatory system via the unidirectional lymphatic system. Lymphatic capillaries drain fluid, proteins, and cells from tissues and transport this lymph fluid through collecting lymphatic ducts toward lymph nodes. Eventually lymphatic fluid from the right and left lymphatic ducts joins the subclavian veins and recirculates throughout the circulatory system. These two intricate vascular systems, working in cooperation, help to maintain essential bodily functions such as fluid dynamics, tissue homeostasis, blood pressure, metabolism, and immunity. However, dysfunction of these systems is associated with a host of pathological conditions, including cardiovascular diseases, obesity, retinopathy, hypoxia, necrosis, and vascular malformations.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792095","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}
Pub Date : 2025-03-03DOI: 10.1101/cshperspect.a041548
Alina M Winkelkotte, Kamal Al-Shami, Adriano B Chaves-Filho, Felix C E Vogel, Almut Schulze
Lipids have essential functions as structural components of cellular membranes, as efficient energy storage molecules, and as precursors of signaling mediators. While deregulated glucose and amino acid metabolism in cancer have received substantial attention, the roles of lipids in the metabolic reprogramming of cancer cells are less well understood. However, since the first description of de novo fatty acid biosynthesis in cancer tissues almost 70 years ago, numerous studies have investigated the complex functions of altered lipid metabolism in cancer. Here, we will summarize the mechanisms by which oncogenic signaling pathways regulate fatty acid and cholesterol metabolism to drive rapid proliferation and protect cancer cells from environmental stress. The review also discusses the role of fatty acid metabolism in metabolic plasticity required for the adaptation to changing microenvironments during cancer progression and the connections between fatty acid and cholesterol metabolism and ferroptosis.
{"title":"Interactions of Fatty Acid and Cholesterol Metabolism with Cellular Stress Response Pathways in Cancer.","authors":"Alina M Winkelkotte, Kamal Al-Shami, Adriano B Chaves-Filho, Felix C E Vogel, Almut Schulze","doi":"10.1101/cshperspect.a041548","DOIUrl":"10.1101/cshperspect.a041548","url":null,"abstract":"<p><p>Lipids have essential functions as structural components of cellular membranes, as efficient energy storage molecules, and as precursors of signaling mediators. While deregulated glucose and amino acid metabolism in cancer have received substantial attention, the roles of lipids in the metabolic reprogramming of cancer cells are less well understood. However, since the first description of de novo fatty acid biosynthesis in cancer tissues almost 70 years ago, numerous studies have investigated the complex functions of altered lipid metabolism in cancer. Here, we will summarize the mechanisms by which oncogenic signaling pathways regulate fatty acid and cholesterol metabolism to drive rapid proliferation and protect cancer cells from environmental stress. The review also discusses the role of fatty acid metabolism in metabolic plasticity required for the adaptation to changing microenvironments during cancer progression and the connections between fatty acid and cholesterol metabolism and ferroptosis.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476106","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}
Pub Date : 2025-02-10DOI: 10.1101/cshperspect.a041621
Vilas Menon
Within the last three decades, revolutions in genomics data generation and bioinformatics analysis techniques have profoundly impacted our understanding of the molecular mechanisms of Parkinson's disease (PD). From the description of the first PD-associated risk gene in 1997 through today, new technologies have revolutionized approaches to identify genetic and molecular mechanisms implicated in human health and disease. Spurred by the dramatically decreasing costs for genotyping, genome sequencing, and transcriptomics approaches, the ability to profile large cohorts of human populations or model organisms has accelerated the understanding of disease susceptibility, pathways, and genes. Thus far, ∼30 genetic loci have been unequivocally linked to the pathogenesis of PD, highlighting essential molecular pathways underlying this common disorder. More recently, the advent of single-cell transcriptomics techniques applied to human brain tissue has implicated cell-type-specific dysregulation and vulnerability (beyond the loss of dopaminergic neurons) in the disease. Herein, we discuss how neurogenomics and bioinformatics are applied to dissect the nature of this complex disease with the overall aim of identifying new targets for therapeutic interventions.
{"title":"Exploring Parkinson's through the Lens of Genomics and Bioinformatics.","authors":"Vilas Menon","doi":"10.1101/cshperspect.a041621","DOIUrl":"https://doi.org/10.1101/cshperspect.a041621","url":null,"abstract":"<p><p>Within the last three decades, revolutions in genomics data generation and bioinformatics analysis techniques have profoundly impacted our understanding of the molecular mechanisms of Parkinson's disease (PD). From the description of the first PD-associated risk gene in 1997 through today, new technologies have revolutionized approaches to identify genetic and molecular mechanisms implicated in human health and disease. Spurred by the dramatically decreasing costs for genotyping, genome sequencing, and transcriptomics approaches, the ability to profile large cohorts of human populations or model organisms has accelerated the understanding of disease susceptibility, pathways, and genes. Thus far, ∼30 genetic loci have been unequivocally linked to the pathogenesis of PD, highlighting essential molecular pathways underlying this common disorder. More recently, the advent of single-cell transcriptomics techniques applied to human brain tissue has implicated cell-type-specific dysregulation and vulnerability (beyond the loss of dopaminergic neurons) in the disease. Herein, we discuss how neurogenomics and bioinformatics are applied to dissect the nature of this complex disease with the overall aim of identifying new targets for therapeutic interventions.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390320","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}
Pub Date : 2025-02-10DOI: 10.1101/cshperspect.a041585
Kayla V Hamilton, Akiko Shimamura, Jessica A Pollard
Hematologic malignancies (HMs) have been increasingly recognized in association with an underlying genetic predisposition syndrome (GPS) in individuals of all ages. It is critical for hematology and oncology providers to be aware of the diagnostic findings, physical examination findings, and aspects of family history that raise suspicion for an underlying GPS. Moreover, recognition of how somatic gene panel testing, frequently done at the time of HM diagnosis, may raise suspicion for an underlying germline condition based on the mutation profile reported, is prudent. With knowledge of an underlying germline condition, the chemotherapy used for a given HM may be impacted and the role of hematopoietic stem cell transplant more critically considered. Off-therapy monitoring after HM treatment is completed will also likely be impacted. In this work, we review key features of several GPSs associated with increased risks for HM while also outlining the diagnostic workup to identify GPSs and treatment considerations for affected patients. Armed with this knowledge, treating providers may evaluate the possibility of a GPS in patients with leukemia/lymphoma and modify their treatment plan accordingly.
{"title":"Genetic Predisposition to Hematologic Malignancies.","authors":"Kayla V Hamilton, Akiko Shimamura, Jessica A Pollard","doi":"10.1101/cshperspect.a041585","DOIUrl":"https://doi.org/10.1101/cshperspect.a041585","url":null,"abstract":"<p><p>Hematologic malignancies (HMs) have been increasingly recognized in association with an underlying genetic predisposition syndrome (GPS) in individuals of all ages. It is critical for hematology and oncology providers to be aware of the diagnostic findings, physical examination findings, and aspects of family history that raise suspicion for an underlying GPS. Moreover, recognition of how somatic gene panel testing, frequently done at the time of HM diagnosis, may raise suspicion for an underlying germline condition based on the mutation profile reported, is prudent. With knowledge of an underlying germline condition, the chemotherapy used for a given HM may be impacted and the role of hematopoietic stem cell transplant more critically considered. Off-therapy monitoring after HM treatment is completed will also likely be impacted. In this work, we review key features of several GPSs associated with increased risks for HM while also outlining the diagnostic workup to identify GPSs and treatment considerations for affected patients. Armed with this knowledge, treating providers may evaluate the possibility of a GPS in patients with leukemia/lymphoma and modify their treatment plan accordingly.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390338","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}