22 papers · ranked by Valyu relevance
Christopher R. Ireson, Mo S. Alavijeh, Alan M. Palmer, Emily R. Fowler + 1 more
'Emily R. Fowler' 'Hazel J. Jones'] Our understanding of cancer biology has increased substantially over the past 30 years. Despite this, and an increasing pharmaceutical company expenditure on research and development, the approval of novel oncology drugs during the past decade continues to be modest. In addition, the…
Haochuan Guo, Xinru Xu, Jiaxi Zhang, Yajing Du + 7 more
'Zhiheng He' 'Linjie Zhao' 'Tingming Liang' 'Li Guo' 'Fuyi Wang' 'Andréia Machado Leopoldino'] The establishment and utilization of preclinical animal models constitute a pivotal aspect across all facets of cancer research, indispensably contributing to the comprehension of disease initiation and progression…
Lesley A. Ogilvie, Aleksandra Kovachev, Christoph Wierling, Bodo M. H. Lange + 1 more
'Bodo M. H. Lange' 'Hans Lehrach'] Every patient and every disease is different. Each patient therefore requires a personalized treatment approach. For technical reasons, a personalized approach is feasible for treatment strategies such as surgery, but not for drug-based therapy or drug development. The development of…
Lorenzo, Guillermo, Hormuth, David A. + 16 more
Despite advances in methods to interrogate tumor biology, the observational and population-based approach of classical cancer research and clinical oncology does not enable anticipation of tumor outcomes to hasten the discovery of cancer mechanisms and personalize disease management. To address these limitations…
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This study presents a novel in vitro 3D hepatocyte model that contains a nanofibrous scaffold designed to mimic the extracellular matrix (ECM) of the human liver, both structurally and biochemically. A modular 3D-printed device housing the ECM scaffold was also developed, readily fitting in well plates. HepaRG…
Scott Gigante, Varsha G. Raghavan, Amanda M. Robinson, Robert A. Barton + 6 more
'Robert A. Barton' 'Adeeb Rahman' 'Drausin Wulsin' 'Jacques Banchereau' 'Noam Solomon' 'Luis Voloch' 'Fabian J. Theis'] Translating the relevance of preclinical models (in vitro, animal models, or organoids) to their relevance in humans presents an important challenge during drug development. The rising abundance of…
Elizabeth Pan, David Bogumil, Victoria Cortessis, Sherrie Yu + 1 more
Preclinical cell models are the mainstay in the early stages of drug development. We sought to explore the preclinical data that differentiated successful from failed therapeutic agents in lung cancer. 134 failed lung cancer drugs and 27 successful lung cancer drugs were identified. Preclinical data were evaluated. The…
Vibeke Fosse, Emanuela Oldoni, Chiara Gerardi, Rita Banzi + 6 more
The introduction of personalized medicine, through the increasing multi-omics characterization of disease, brings new challenges to disease modeling. The scope of this review was a broad evaluation of the relevance, validity, and predictive value of the current preclinical methodologies applied in stratified medicine…
Avery S. Williams, Elizabeth J. Wilk, Jennifer L. Fisher, Brittany N. Lasseigne
Preclinical models like cancer cell lines and patient-derived xenografts (PDXs) are vital for studying disease mechanisms and evaluating treatment options. It is essential that they accurately recapitulate the disease state of interest to generate results that will translate in the clinic. Prior studies have…
Natalia V. Segatto, Mariana H. Remião, Kyle M. Schachtschneider, Fabiana K. Seixas + 2 more
'Fabiana K. Seixas' 'Lawrence B. Schook' 'Tiago Collares'] The screening of potential therapeutic compounds using phenotypic drug discovery (PDD) is being embraced once again by researchers and pharmaceutical companies as an approach to enhance the development of new effective therapeutics. Before the genomics and…
David Andreu-Sanz, Lisa Gregor, Emanuele Carlini, Daniele Scarcella + 2 more
Experimental mouse models are indispensable for the preclinical development of cancer immunotherapies, whereby complex interactions in the tumor microenvironment (TME) can be somewhat replicated. Despite the availability of diverse models, their predictive capacity for clinical outcomes remains largely unknown, posing…
Rachel Blomberg, Kayla Sompel, Caroline Hauer, Brisa Peña + 5 more
Lung cancer is the leading global cause of cancer-related deaths. Although smoking cessation is the best preventive action, nearly 50% of all lung cancer diagnoses occur in people who have already quit smoking. Research into treatment options for these high-risk patients has been constrained to rodent models of…
Caroline Hauer, Rachel Blomberg, Kayla Sompel, Chelsea M. Magin + 1 more
Lung cancer is the leading cause of global cancer death and prevention strategies are key to reducing mortality. Medical prevention may have a larger impact than treatment on mortality by targeting high-risk populations and reducing their lung cancer risk. Premalignant lesions (PMLs) that can be intercepted by…
Sandrine Boulet, Moreno Ursino, Robin Michelet, Linda B. S. Aulin + 3 more
'Charlotte Kloft' 'Emmanuelle Comets' 'Sarah Zohar'] In preclinical investigations, e.g. in in vitro, in vivo and in silico studies, the pharmacokinetic, pharmacodynamic and toxicological characteristics of a drug are evaluated before advancing to firstin-man trial. Usually, each study is analyzed independently and the…
S. Benzekry, M. Mastri, C. Nicolò, J. ML Ebos
Clinical trials involving systemic neoadjuvant treatments in breast cancer aim to shrink tumors prior to surgery while simultaneously allowing for controlled evaluation of biomarkers, toxicity, and suppression of distant (occult) metastatic disease. Yet such trials are rarely preceded by preclinical testing involving…
Niall Shanks, Ray Greek, Jean Greek
It is one of the central aims of the philosophy of science to elucidate the meanings of scientific terms and also to think critically about their application. The focus of this essay is the scientific term predict and whether there is credible evidence that animal models, especially in toxicology and pathophysiology…
Marco Viceconti, Luca Emili, Payman Afshari, Eulalie Courcelles + 14 more
'Cristina Curreli' 'Nele Famaey' 'Liesbet Geris' 'Marc Horner' 'Maria Cristina Jori' 'Alexander Kulesza' 'Axel Loewe' 'Michael Neidlin' 'Markus Réitérer' 'Cécile F. Rousseau' 'Giulia Russo' 'Simon J. Sonntag' 'Emmanuelle Voisin' 'Francesco Pappalardo'] Abstract—The term "In Silico Trial" indicates the use of computer…
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Accurate modeling of drug concentration--time (C--t) profiles is central to pharmacokinetics (PK) and plays a critical role in both early-stage compound selection and late-stage individualized dosing. Traditional PK model offer mechanistic interpretability but often rely on rigid assumptions, extensive…
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This paper explores the transformative potential of Artificial Intelligence (AI) in enabling in silico clinical trials (ISCTs) for vaccine development. ISCTs, which simulate clinical trials using virtual patient cohorts, offer a cost-effective, ethical, and efficient alternative to traditional methods. AI significantly…
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Integrating machine learning (ML) into drug discovery has ushered in a new era of innovation, dramatically enhancing the efficiency and precision of identifying and developing new therapeutics. This review provides a comprehensive analysis of the current applications of machine learning in drug discovery, focusing on…
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Failures in drug discovery due to intolerable levels of adverse effects remain a significant concern. These failures can profoundly impact drug development, especially when identified during the later stages. Despite the challenges and risks posed by unexpected late-stage toxicity, publicly available data and…
Carley V. Cook, Ariel M. Lighty, Brenda J. Smith, Ashlee N. Ford Versypt
Bone remodeling is an essential physiological process in the adult skeleton. Due to the complex nature of this process, many mathematical models of bone remodeling have been developed. Each of these models has unique features, but they have underlying patterns. In this review, the authors highlight the important…