Cancer research

Authors:

Paul Workman

Eric O. Aboagye

Frances R. Balkwill

Allan Balmain

Gail Bruder

David J. Chaplin

John A. Double

Jeffrey I. Everitt

D. A. H. Farningham

Martin J. Glennie

Lloyd R. Kelland

Vicky Robinson

Ian J. Stratford

Gillian M. Tozer

Susan A. Watson

Stephen R. Wedge

Suzanne A. Eccles

National Cancer, Research Institute

Publication:

British Journal of Cancer 102, 1555–1577

Publish Date:

25 September 2010

Background

Animals are widely used in cancer research for the prevention, diagnosis, and development of treatments. Protecting the welfare of animals in cancer research is crucial for both ethical reasons and to maintain scientific integrity. Previous guidelines have been published in the 80s and 90s, but have now become obsolete, necessitating an update due to scientific advancements.

Summary

This article provides new guidelines for the cancer research community, with a strong focus on animal welfare, particularly concerning rodents. These guidelines provide advice on the 3Rs (Replacement, Reduction, Refinement) and cover recommendations on various aspects of cancer research, including study design, statistics, pilot studies, selection of tumour models (such as genetically engineered, orthotopic, and metastatic models), therapy (drugs and radiation), imaging techniques (including anaesthesia and restraint), humane endpoints (e.g. tumour burden and site), and publication of best practice.

Key Actions

Study design should be scientifically robust, employ appropriate statistical methods, and include pilot studies to define experimental and humane endpoints.
The choice of tumour models should be tailored to the scientific question.
Humane endpoints must be established to minimise adverse effects and death as an endpoint is unacceptable.

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Further questions

With solid tumours, humane endpoints should include maximum scores for ulceration, distension of covering tissues and cachexia (severe body weight loss). If an animal has a single tumour, the mean diameter should not normally exceed 1.2 cm in mice or 2.5 cm in rats, or 1.5 and 2.8 cm, respectively, for therapeutic studies.
There are several factors that can be refined, including:
- For subcutaneous implantation, optimise anaesthesia and analgesia
- For cell suspension injections, use the minimum number of cells in the smallest volume consistent with the tumour properties
- Select the site carefully, e.g. ensure mobility will not be affected when the tumour grows
- If hormone pellets are used, conduct pilot studies to check for tolerance and adverse effects
- Ensure there are clear, refined humane endpoints for tumour size and ulceration

Authors

Paul Workman - The Institute of Cancer Research

Eric O. Aboagye - Imperial College London

Frances R. Balkwill - Barts and The London School of Medicine and Dentistry

Allan Balmain - University of California San Francisco

Gail Bruder - University of Manchester

David J. Chaplin - OXiGENE Inc.

John A. Double - University of Bradford

Jeffrey I. Everitt - GlaxoSmithkline Pharmaceutical R&D

D. A. H. Farningham - Cancer Research UK

Martin J. Glennie - Southampton University

Lloyd R. Kelland - University College London

Vicky Robinson - National Centre for the Replacement, Refinement and Reduction of Animals in Research

Ian J. Stratford - University of Manchester

Gillian M. Tozer - University of Sheffield

Susan A. Watson - Nottingham University Hospital

Stephen R. Wedge - AstraZeneca

Suzanne A. Eccles - The Institute of Cancer Research

Ad hoc committe of the National Cancer Research Institute