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CA: a Cancer Journal For Clinicians Mar 2017The American Joint Committee on Cancer (AJCC) staging manual has become the benchmark for classifying patients with cancer, defining prognosis, and determining the best...
The American Joint Committee on Cancer (AJCC) staging manual has become the benchmark for classifying patients with cancer, defining prognosis, and determining the best treatment approaches. Many view the primary role of the tumor, lymph node, metastasis (TNM) system as that of a standardized classification system for evaluating cancer at a population level in terms of the extent of disease, both at initial presentation and after surgical treatment, and the overall impact of improvements in cancer treatment. The rapid evolution of knowledge in cancer biology and the discovery and validation of biologic factors that predict cancer outcome and response to treatment with better accuracy have led some cancer experts to question the utility of a TNM-based approach in clinical care at an individualized patient level. In the Eighth Edition of the AJCC Cancer Staging Manual, the goal of including relevant, nonanatomic (including molecular) factors has been foremost, although changes are made only when there is strong evidence for inclusion. The editorial board viewed this iteration as a proactive effort to continue to build the important bridge from a "population-based" to a more "personalized" approach to patient classification, one that forms the conceptual framework and foundation of cancer staging in the era of precision molecular oncology. The AJCC promulgates best staging practices through each new edition in an effort to provide cancer care providers with a powerful, knowledge-based resource for the battle against cancer. In this commentary, the authors highlight the overall organizational and structural changes as well as "what's new" in the Eighth Edition. It is hoped that this information will provide the reader with a better understanding of the rationale behind the aggregate proposed changes and the exciting developments in the upcoming edition. CA Cancer J Clin 2017;67:93-99. © 2017 American Cancer Society.
Topics: Diagnostic Imaging; Humans; Lymphatic Metastasis; Neoplasm Staging; Practice Guidelines as Topic; Precision Medicine; Terminology as Topic; United States
PubMed: 28094848
DOI: 10.3322/caac.21388 -
Nature Reviews. Drug Discovery Feb 2021In recent years, the development of nanoparticles has expanded into a broad range of clinical applications. Nanoparticles have been developed to overcome the limitations... (Review)
Review
In recent years, the development of nanoparticles has expanded into a broad range of clinical applications. Nanoparticles have been developed to overcome the limitations of free therapeutics and navigate biological barriers - systemic, microenvironmental and cellular - that are heterogeneous across patient populations and diseases. Overcoming this patient heterogeneity has also been accomplished through precision therapeutics, in which personalized interventions have enhanced therapeutic efficacy. However, nanoparticle development continues to focus on optimizing delivery platforms with a one-size-fits-all solution. As lipid-based, polymeric and inorganic nanoparticles are engineered in increasingly specified ways, they can begin to be optimized for drug delivery in a more personalized manner, entering the era of precision medicine. In this Review, we discuss advanced nanoparticle designs utilized in both non-personalized and precision applications that could be applied to improve precision therapies. We focus on advances in nanoparticle design that overcome heterogeneous barriers to delivery, arguing that intelligent nanoparticle design can improve efficacy in general delivery applications while enabling tailored designs for precision applications, thereby ultimately improving patient outcome overall.
Topics: Biomedical Engineering; Drug Delivery Systems; Humans; Nanoparticles; Pharmaceutical Preparations; Precision Medicine
PubMed: 33277608
DOI: 10.1038/s41573-020-0090-8 -
Epilepsia Mar 2021Precision medicine in the epilepsies has gathered much attention, especially with gene discovery pushing forward new understanding of disease biology. Several targeted... (Review)
Review
Precision medicine in the epilepsies has gathered much attention, especially with gene discovery pushing forward new understanding of disease biology. Several targeted treatments are emerging, some with considerable sophistication and individual-level tailoring. There have been rare achievements in improving short-term outcomes in a few very select patients with epilepsy. The prospects for further targeted, repurposed, or novel treatments seem promising. Along with much-needed success, difficulties are also arising. Precision treatments do not always work, and sometimes are inaccessible or do not yet exist. Failures of precision medicine may not find their way to broader scrutiny. Precision medicine is not a new concept: It has been boosted by genetics and is often focused on genetically determined epilepsies, typically considered to be driven in an individual by a single genetic variant. Often the mechanisms generating the full clinical phenotype from such a perceived single cause are incompletely understood. The impact of additional genetic variation and other factors that might influence the clinical presentation represent complexities that are not usually considered. Precision success and precision failure are usually equally incompletely explained. There is a need for more comprehensive evaluation and a more rigorous framework, bringing together information that is both necessary and sufficient to explain clinical presentation and clinical responses to precision treatment in a precision approach that considers the full picture not only of the effects of a single variant, but also of its genomic and other measurable environment, within the context of the whole person. As we may be on the brink of a treatment revolution, progress must be considered and reasoned: One possible framework is proposed for the evaluation of precision treatments.
Topics: Epilepsy; Forecasting; Genetic Variation; Humans; Mutation; Pedigree; Precision Medicine
PubMed: 32776321
DOI: 10.1111/epi.16539 -
The European Respiratory Journal Oct 2017The term "precision medicine" has become very popular over recent years, fuelled by scientific as well as political perspectives. Despite its popularity, its exact... (Review)
Review
The term "precision medicine" has become very popular over recent years, fuelled by scientific as well as political perspectives. Despite its popularity, its exact meaning, and how it is different from other popular terms such as "stratified medicine", "targeted therapy" or "deep phenotyping" remains unclear. Commonly applied definitions focus on the stratification of patients, sometimes referred to as a novel taxonomy, and this is derived using large-scale data including clinical, lifestyle, genetic and further biomarker information, thus going beyond the classical "signs-and-symptoms" approach.While these aspects are relevant, this description leaves open a number of questions. For example, when does precision medicine begin? In which way does the stratification of patients translate into better healthcare? And can precision medicine be viewed as the end-point of a novel stratification of patients, as implied, or is it rather a greater whole?To clarify this, the aim of this paper is to provide a more comprehensive definition that focuses on precision medicine as a process. It will be shown that this proposed framework incorporates the derivation of novel taxonomies and their role in healthcare as part of the cycle, but also covers related terms.
Topics: Classification; Comprehensive Health Care; Humans; Precision Medicine
PubMed: 29051268
DOI: 10.1183/13993003.00391-2017 -
Fertility and Sterility Jun 2018There is a great deal of hype surrounding the concept of personalized medicine. Personalized medicine is rooted in the belief that since individuals possess nuanced and... (Review)
Review
There is a great deal of hype surrounding the concept of personalized medicine. Personalized medicine is rooted in the belief that since individuals possess nuanced and unique characteristics at the molecular, physiological, environmental exposure, and behavioral levels, they may need to have interventions provided to them for diseases they possess that are tailored to these nuanced and unique characteristics. This belief has been verified to some degree through the application of emerging technologies such as DNA sequencing, proteomics, imaging protocols, and wireless health monitoring devices, which have revealed great inter-individual variation in disease processes. In this review, we consider the motivation for personalized medicine, its historical precedents, the emerging technologies that are enabling it, some recent experiences including successes and setbacks, ways of vetting and deploying personalized medicines, and future directions, including potential ways of treating individuals with fertility and sterility issues. We also consider current limitations of personalized medicine. We ultimately argue that since aspects of personalized medicine are rooted in biological realities, personalized medicine practices in certain contexts are likely to be inevitable, especially as relevant assays and deployment strategies become more efficient and cost-effective.
Topics: Cost-Benefit Analysis; Humans; Motivation; Precision Medicine; Reproductive Techniques, Assisted; Research Design
PubMed: 29935653
DOI: 10.1016/j.fertnstert.2018.05.006 -
Cell Mar 2019In the wake of the Human Genome Project (HGP), strong expectations were set for the timeline and impact of genomics on medicine-an anticipated transformation in the... (Review)
Review
In the wake of the Human Genome Project (HGP), strong expectations were set for the timeline and impact of genomics on medicine-an anticipated transformation in the diagnosis, treatment, and prevention of disease. In this Perspective, we take stock of the nascent field of genomic medicine. In what areas, if any, is genomics delivering on this promise, or is the path to success clear? Where are we falling short, and why? What have been the unanticipated developments? Overall, we argue that the optimism surrounding the transformational potential of genomics on medicine remains justified, albeit with a considerably different form and timescale than originally projected. We also argue that the field needs to pivot back to basics, as understanding the entirety of the genotype-to-phenotype equation is a likely prerequisite for delivering on the full potential of the human genome to advance the human condition.
Topics: Genetic Testing; Genome, Human; Genomics; Human Genome Project; Humans; Precision Medicine
PubMed: 30901547
DOI: 10.1016/j.cell.2019.02.003 -
Genome Apr 2021Precision medicine is an emerging approach to clinical research and patient care that focuses on understanding and treating disease by integrating multi-modal or... (Review)
Review
Precision medicine is an emerging approach to clinical research and patient care that focuses on understanding and treating disease by integrating multi-modal or multi-omics data from an individual to make patient-tailored decisions. With the large and complex datasets generated using precision medicine diagnostic approaches, novel techniques to process and understand these complex data were needed. At the same time, computer science has progressed rapidly to develop techniques that enable the storage, processing, and analysis of these complex datasets, a feat that traditional statistics and early computing technologies could not accomplish. Machine learning, a branch of artificial intelligence, is a computer science methodology that aims to identify complex patterns in data that can be used to make predictions or classifications on new unseen data or for advanced exploratory data analysis. Machine learning analysis of precision medicine's multi-modal data allows for broad analysis of large datasets and ultimately a greater understanding of human health and disease. This review focuses on machine learning utilization for precision medicine's "big data", in the context of genetics, genomics, and beyond.
Topics: Artificial Intelligence; Genomics; Humans; Machine Learning; Precision Medicine
PubMed: 33091314
DOI: 10.1139/gen-2020-0131 -
Current Opinion in Pediatrics Feb 2018The current review describes recent advances and unique challenges in precision medicine for pediatric cancers and highlights clinical trials assessing the clinical... (Review)
Review
PURPOSE OF REVIEW
The current review describes recent advances and unique challenges in precision medicine for pediatric cancers and highlights clinical trials assessing the clinical impact of targeted therapy matched to molecular alterations identified by tumor profiling.
RECENT FINDINGS
Multiple prospective clinical sequencing studies in pediatric oncology have been reported in the last 2 years. These studies demonstrated feasibility of sequencing in the clinic and revealed a rate of actionable variants that justifies the development of precision trials for childhood cancer. A number of precision medicine trials are recently completed, underway or in development and these will be reviewed herein, with a focus on highlighting aspects of precision medicine trial design relevant to pediatric oncology.
SUMMARY
The primary results of the first round of pediatric precision oncology clinical trials will provide us with a greater understanding of the clinical impact of linking tumor profiling to selection of targeted therapies. The aggregation of sequencing and clinical data from these trials and the results of biologic investigations linked to these trials will drive further discoveries and broaden opportunities for precision medicine for children with cancer.
Topics: Antineoplastic Agents; Biomarkers, Tumor; Child; Humans; Medical Oncology; Molecular Targeted Therapy; Neoplasms; Pediatrics; Precision Medicine
PubMed: 29189430
DOI: 10.1097/MOP.0000000000000570 -
Neurotherapeutics : the Journal of the... Apr 2020Epilepsy includes a number of medical conditions with recurrent seizures as common denominator. The large number of different syndromes and seizure types as well as the... (Review)
Review
Epilepsy includes a number of medical conditions with recurrent seizures as common denominator. The large number of different syndromes and seizure types as well as the highly variable inter-individual response to the therapies makes management of this condition often challenging. In the last two decades, a genetic etiology has been revealed in more than half of all epilepsies and single gene defects in ion channels or neurotransmitter receptors have been associated with most inherited forms of epilepsy, including some focal and lesional forms as well as specific epileptic developmental encephalopathies. Several genetic tests are now available, including targeted assays up to revolutionary tools that have made sequencing of all coding (whole exome) and non-coding (whole genome) regions of the human genome possible. These recent technological advances have also driven genetic discovery in epilepsy and increased our understanding of the molecular mechanisms of many epileptic disorders, eventually providing targets for precision medicine in some syndromes, such as Dravet syndrome, pyroxidine-dependent epilepsy, and glucose transporter 1 deficiency. However, these examples represent a relatively small subset of all types of epilepsy, and to date, precision medicine in epilepsy has primarily focused on seizure control, and other clinical aspects, such as neurodevelopmental and neuropsychiatric comorbidities, have yet been possible to address. We herein summarize the most recent advances in genetic testing and provide up-to-date approaches for the choice of the correct test for some epileptic disorders and tailored treatments that are already applicable in some monogenic epilepsies. In the next years, the most probably scenario is that epilepsy treatment will be very different from the currently almost empirical approach, eventually with a "precision medicine" approach applicable on a large scale.
Topics: Epilepsy; Genetic Testing; Humans; Precision Medicine
PubMed: 31981099
DOI: 10.1007/s13311-020-00835-4 -
Journal of Diabetes Investigation Sep 2018Diabetes has become a major burden of healthcare expenditure. Diabetes management following a uniform treatment algorithm is often associated with progressive treatment... (Review)
Review
Diabetes has become a major burden of healthcare expenditure. Diabetes management following a uniform treatment algorithm is often associated with progressive treatment failure and development of diabetic complications. Recent advances in our understanding of the genomic architecture of diabetes and its complications have provided the framework for development of precision medicine to personalize diabetes prevention and management. In the present review, we summarized recent advances in the understanding of the genetic basis of diabetes and its complications. From a clinician's perspective, we attempted to provide a balanced perspective on the utility of genomic medicine in the field of diabetes. Using genetic information to guide management of monogenic forms of diabetes represents the best-known examples of genomic medicine for diabetes. Although major strides have been made in genetic research for diabetes, its complications and pharmacogenetics, ongoing efforts are required to translate these findings into practice by incorporating genetic information into a risk prediction model for prioritization of treatment strategies, as well as using multi-omic analyses to discover novel drug targets with companion diagnostics. Further research is also required to ensure the appropriate use of this information to empower individuals and healthcare professionals to make personalized decisions for achieving the optimal outcome.
Topics: Diabetes Mellitus; Disease Management; Humans; Pharmacogenetics; Precision Medicine; Risk Factors
PubMed: 29499103
DOI: 10.1111/jdi.12830