Pre-Clinical Research

While much of basic science is conducted in vitro (in glass test tubes), early translational research is often in vivo (living organisms).

CISN TIP: Vitro = tube Vivo = living

Since the 1800s mice have often been used in pre-clinical cancer research. This is because mice are:

• Relatively easy and inexpensive to maintain
• Reproduce rapidly
• Possess considerable genetic similarity to humans

Over time, specialized mice have been developed that have allowed scientists to more easily induce cancer and/or to turn on or off certain genes, exploring their impact on cancer development and subsequently, the effect of various treatments.

Genetically Altered Mice

Inbred Strains: Specialized mouse strains that are genetically identical and predisposed to develop specific cancers Knockout Mice: Genetically engineered mice in which one or more genes have been turned off Transgenic Mice: Mice that have been genetically altered as embryos. These animals are very useful for delineating the function of newly discovered genes.

 

Immune Deficient Mice

Since the 1960s, scientists have been able to breed mice that have deficient immune systems with no functional T-or B-cells. Human cancer cells that are implanted into these mice are not rejected, as they would be in mice with normal immune systems. Thus, the natural history of untreated human cancers, as well as the impact of various treatments can be studied in mice.

	Nude Mice: Hairless mutant mice that are immune deficient were developed in 1937. They do not reject tumor transplantations from other species, allowing actual human tumors to be studied in a whole animal system.

• SCID Mice: Mice with severe combined immune deficiency (SCID) were discovered in 1983. SCID mice are even more immune deficient than nude mice. Tumors from other species are easily transplanted into SCID mice and will grow without being rejected.

Xenografts & Mouse Models

The use of xenografts in mouse models has led to much better prediction about how cancer actually behaves in humans.

Tissue or organs from an individual of one species is transplanted into or grafted onto an organism of another species, genus, or family. So in this picture you see a mouse that had cells from a human tumor injected into it. The cells grew into a tumor in the mouse and then the mouse was given a new drug to observe the effect.

Still, many new treatments that appear quite effective in these models either don't work in humans, or prove to be too toxic.