scholarly journals The role of preclinical animal models in breast cancer drug development

2009 ◽  
Vol 11 (S3) ◽  
Author(s):  
Robert Clarke
Keyword(s):  
Breast Cancer ◽  
Animal Models ◽  
Drug Development ◽  
Cancer Drug ◽  
Preclinical Animal Models

Prevascularized, Co-Culture Model for Breast Cancer Drug Development

2012 ◽  
Author(s):  
Lauren Marshall ◽  
Isabel Löwstedt ◽  
Paul Gatenholm ◽  
Joel Berry
Keyword(s):  
Breast Cancer ◽  
Drug Development ◽  
Three Dimensional ◽  
Human Tumor ◽  
3D Models ◽  
Cancer Drug ◽  
Cancer Therapies ◽  
Anti Cancer

The objective of this study was to create 3D engineered tissue models to accelerate identification of safe and efficacious breast cancer drug therapies. It is expected that this platform will dramatically reduce the time and costs associated with development and regulatory approval of anti-cancer therapies, currently a multi-billion dollar endeavor [1]. Existing two-dimensional (2D) in vitro and in vivo animal studies required for identification of effective cancer therapies account for much of the high costs of anti-cancer medications and health insurance premiums borne by patients, many of whom cannot afford it. An emerging paradigm in pharmaceutical drug development is the use of three-dimensional (3D) cell/biomaterial models that will accurately screen novel therapeutic compounds, repurpose existing compounds and terminate ineffective ones. In particular, identification of effective chemotherapies for breast cancer are anticipated to occur more quickly in 3D in vitro models than 2D in vitro environments and in vivo animal models, neither of which accurately mimic natural human tumor environments [2]. Moreover, these 3D models can be multi-cellular and designed with extracellular matrix (ECM) function and mechanical properties similar to that of natural in vivo cancer environments [3].

scholarly journals Role of breast cancer resistance protein (BCRP/ABCG2) in cancer drug resistance

2012 ◽  
Vol 83 (8) ◽  
pp. 1084-1103 ◽  
Author(s):  
Karthika Natarajan ◽  
Yi Xie ◽  
Maria R. Baer ◽  
Douglas D. Ross
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Breast Cancer Resistance Protein ◽  
Cancer Drug ◽  
Cancer Resistance ◽  
Cancer Drug Resistance ◽  
Resistance Protein

scholarly journals Approaching 3R teaching in biomedical engineering

2020 ◽  
Author(s):  
Valeria Chiono
Keyword(s):  
Animal Models ◽  
Biomedical Engineering ◽  
Experimental Models ◽  
Preclinical Testing ◽  
Preclinical Trials ◽  
European Standards ◽  
Preclinical Animal Models ◽  
In Silico Models

Since its adhesion to Centro3R, Politecnico di Torino has approached 3R teaching through a new Master course, entitled “New advances in alternative preclinical trials”. This is a multidisciplinary optional course for Master students in Biomedical Engineering, with the contribution of different teachers, who are experts on different aspects of preclinical testing of biomedical devices: European Standards for preclinical experimentation; preclinical animal models; protection of animal welfare in the European legislation; the role of statistics on the application of the 3R principle; preclinical experimental models in vitro; in silico models. This contribution describes the subjects faced by the course and their importance in the context of the 3R Principle.

scholarly journals Clinical, Pathological, and Ethical Considerations for the Conduct of Clinical Trials in Dogs with Naturally Occurring Cancer: A Comparative Approach to Accelerate Translational Drug Development

ILAR Journal ◽  
2018 ◽  
Vol 59 (1) ◽  
pp. 99-110 ◽  
Author(s):  
Daniel Regan ◽  
Kelly Garcia ◽  
Douglas Thamm
Keyword(s):  
Clinical Trials ◽  
Drug Development ◽  
Translational Research ◽  
Cancer Biology ◽  
Comparative Approach ◽  
Cancer Drug ◽  
Comparative Oncology ◽  
Pet Dogs ◽  
Naturally Occurring

Abstract The role of comparative oncology in translational research is receiving increasing attention from drug developers and the greater biomedical research community. Pet dogs with spontaneous cancer are important and underutilized translational models, owing to dogs’ large size and relative outbreeding, combined with their high incidence of certain tumor histotypes with significant biological, genetic, and histological similarities to their human tumor counterparts. Dogs with spontaneous tumors naturally develop therapy resistance and spontaneous metastasis, all in the context of an intact immune system. These fundamental features of cancer biology are often lacking in induced or genetically engineered preclinical tumor models and likely contribute to their poor predictive value and the associated overall high failure rate in oncology drug development. Thus, the conduct of clinical trials in pet dogs with naturally occurring cancer represents a viable surrogate and valuable intermediary step that should be increasingly incorporated into the cancer drug discovery and development pipeline. The development of molecular-targeted therapies has resulted in an expanded role of the pathologist in human oncology trials, and similarly the expertise of veterinary pathologists will be increasingly valuable to all phases of comparative oncology trial design and conduct. In this review, we provide a framework of clinical, ethical, and pathology-focused considerations for the increasing integration of translational research investigations in dogs with spontaneous cancer as a means to accelerate clinical cancer discovery and drug development.

Patient-derived tumour xenografts as models for breast cancer drug development

2014 ◽  
Vol 26 (6) ◽  
pp. 556-561 ◽  
Author(s):  
Elisabetta Marangoni ◽  
Marie-France Poupon
Keyword(s):  
Breast Cancer ◽  
Drug Development ◽  
Cancer Drug ◽  
Tumour Xenografts

Protein degradation: a validated therapeutic strategy with exciting prospects

2017 ◽  
Vol 61 (5) ◽  
pp. 517-527 ◽  
Author(s):  
Honorine Lebraud ◽  
Tom D. Heightman
Keyword(s):  
Animal Models ◽  
Protein Degradation ◽  
Small Molecules ◽  
Cancer Patients ◽  
Clinical Efficacy ◽  
Therapeutic Strategy ◽  
Substrate Recognition ◽  
Pharmacological Targets ◽  
Preclinical Animal Models

In a time of unprecedented challenges in developing potent, selective and well-tolerated protein inhibitors as therapeutics, drug hunters are increasingly seeking alternative modalities to modulate pharmacological targets. Selective inhibitors are achievable for only a fraction of the proteome, and are not guaranteed to elicit the desired response in patients, especially when pursuing targets identified through genetic knockdown. Targeted protein degradation holds the potential to expand the range of proteins that can be effectively modulated. Drugs inducing protein degradation through misfolding or by modulating cereblon (CRBN) substrate recognition are already approved for treatment of cancer patients. The last decade has seen the development of proteolysis targeting chimeras (PROTACs), small molecules that elicit proteasomal degradation by causing protein polyubiquitination. These have been used to degrade a range of disease-relevant proteins in cells, and some show promising efficacy in preclinical animal models, although their clinical efficacy and tolerability is yet to be proven. This review introduces current strategies for protein degradation with an emphasis on PROTACs and the role of click chemistry in PROTAC research through the formation of libraries of preclicked PROTACs or in-cell click-formed PROTACs (CLIPTACs).

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