Mice and rats are important models in cancer research, offering controlled experimental environments to investigate tumor development and treatment responses. Their genetic similarities to humans, with approximately 95-99% shared genes, make them suitable surrogates for studying complex biological processes in cancer progression. Researchers can also genetically modify these rodents to mimic specific human cancer types, enabling the study of spontaneous tumor development and the evaluation of new diagnostic and therapeutic agents.
Observing Tumors on the Outside
Monitoring tumor growth in mice and rats often begins with non-invasive observations. Caliper measurements are a common method, where the length and width of a palpable tumor are taken to estimate its volume, typically using a formula like (length × width²) / 2. This simple method tracks superficial tumor growth over time, typically performed at least twice weekly for visible subcutaneous tumors.
Visual inspection supplements caliper measurements, noting changes in skin, fur, or general appearance. This assesses overall well-being and identifies external signs of progression like discoloration or ulceration. Body weight changes also indicate overall health, though tumor growth can mask weight loss. These external methods are convenient for frequent monitoring but are limited to visible or palpable tumors, and their accuracy can be influenced by tumor shape and measurement technique.
Seeing Tumors Inside the Body
Advanced imaging techniques visualize internal tumors in living animals without invasive procedures. Magnetic Resonance Imaging (MRI) uses strong magnetic fields and radio waves to create detailed images of soft tissues, effective for delineating tumor boundaries, size, and location within organs. MRI does not expose animals to ionizing radiation, allowing for repeated longitudinal studies.
Computed Tomography (CT) utilizes X-rays to produce cross-sectional images, providing good detail of bone structures and overall anatomical context. Micro-CT systems, designed for small animals, can detect murine lung nodules as small as 0.63 mm³. Positron Emission Tomography (PET) involves injecting a small amount of a radioactive tracer, such as ¹⁸F-FDG (fluorodeoxyglucose), which accumulates in metabolically active areas like tumors. This allows assessment of tumor aggressiveness and metabolic activity, indicating how quickly the tumor is growing or responding to treatment.
Ultrasound imaging uses high-frequency sound waves to generate real-time images of internal tissues, including tumor masses. This method also assesses blood flow within and around the tumor using Doppler-based modes, providing insights into tumor vascularization. Ultrasound offers good spatial and temporal resolution for small animal organs (0.5-2 cm penetration depth), and is non-invasive, making it suitable for frequent monitoring.
Uncovering Tumor Biology at a Deeper Level
To understand tumor biology comprehensively, methods analyzing cellular and molecular characteristics are utilized, often requiring tissue samples. Histopathology involves the microscopic examination of stained tissue sections, typically with hematoxylin and eosin (H&E), to evaluate the tumor’s type, grade, and cellular features. This technique allows pathologists to observe mitotic rate, necrosis, and the overall architecture of the tumor, providing insights into its aggressiveness.
Immunohistochemistry (IHC) builds upon histopathology by using antibodies to detect specific proteins within tumor cells. This method identifies markers associated with cell proliferation, apoptosis, or the presence of specific drug targets. IHC can reveal overexpression of certain proteins that might indicate a tumor’s response to a particular therapy or its potential for metastasis.
Molecular analyses delve even deeper into the tumor’s genetic makeup. Techniques like gene expression profiling can measure the activity of thousands of genes simultaneously, revealing patterns that indicate tumor behavior or resistance to treatment. DNA sequencing (whole-genome or targeted) identifies specific mutations or genetic alterations within tumor cells. These analyses provide a detailed “fingerprint” of the tumor, offering insights into its biological pathways and vulnerabilities not discernible through external observation or imaging alone.
Putting All the Pieces Together
No single assessment method fully understands tumor progression or treatment response in animal models. Researchers combine external observations, advanced imaging, and molecular analyses for a comprehensive picture. Caliper measurements offer frequent, low-cost monitoring of external tumor growth, while imaging techniques like MRI or PET provide non-invasive views of internal tumor size, location, and metabolic activity.
Integrating data from these diverse approaches allows for accurate assessment of how tumors grow, spread, and respond to new therapies. For example, a decrease in tumor volume by MRI could correlate with gene expression changes from molecular analysis, providing a robust understanding of a drug’s mechanism. This multi-modal approach tracks tumor growth kinetics and identifies subtle changes missed by a single method. Ultimately, combining these methods enhances the accuracy and reliability of cancer research findings, guiding the development of more effective treatments.