Probing Cancer Models: Generating and Testing Ideas
The study and manipulation of these models—for example,
exposing them to a potential new drug—can help identify useful
approaches for cancer prevention, detection, diagnosis or
treatment that can then be tested in the clinic. Various techniques
are used to probe cancer models, including but not limited to:
genetic, biochemical and cellular analyses.
The genetic code carries a blueprint that is deciphered by the cell
to produce the various proteins that it uses to function (see
Fig. 4, p. 22). Some genetic alterations result in the generation of
abnormal proteins that can fuel the development of cancer.
Alternatively, they may lead to the loss of other critical proteins that
usually maintain normal cellular functions (see Sidebar on the
Genetic Basis of Cancer). Tremendous technological advances in
recent years have made it possible to rapidly sequence the entire
genome of a cancer to reveal which genetic alterations are present.
Furthermore, these technologies can also detect changes in the
cancer’s epigenome, which is how the DNA is modified and
packaged into chromosomes.
Whether or not the observed genetic and epigenetic changes
contribute to cancer can be examined further by engineering cells
or animals to express the modification and by observing the
resultant changes in cell or animal behaviors. Previously,
researchers studied individual pieces of DNA, proteins and cell
metabolites as they pertain to cell function. Now, as a result of
innovative large-scale approaches, researchers can study the
entire set of DNA, proteins and metabolites in a sample. These new
approaches complement more traditional biochemical methods to
rapidly enhance our understanding of the structure and function of
cancer-associated proteins and their effects on cell behavior.
Figure 5: Follow the Signs to Cancer Prevention,
Detection, Diagnosis and Treatment. Biomarkers
are defined as cellular, biochemical and molecular
(including genetic and epigenetic) characteristics by
which normal and/or abnormal processes can be
recognized and/or monitored. Biomarkers are
measurable in biological materials, such as in
tissues, cells, and/or bodily fluids. Depicted are
examples of biomarkers in clinical use to help
assess a person’s cancer risk, detect a growing
cancer, make a cancer diagnosis, identify those
patients most likely to benefit from a specific
molecularly targeted therapy and modify treatment
decisions. In some cases, the biomarker used to
identify those patients most likely to benefit from a
specific molecularly targeted therapy is the same
biomarker used in the process of developing the
drug. The identification of additional biomarkers to
further improve cancer prevention, detection,
diagnosis and treatment is an area of intense
investigation.
The Genetic Basis of Cancer
One of the greatest advances in cancer research was the
discovery that changes, or mutations, in genes can cause
cancer. The “genetic code”, carried in deoxyribonucleic acid
(DNA) units called bases is packaged into chromosomes that
are passed from parents to offspring. The entirety of a
person’s DNA is called a genome. The genetic code within our
genome is decoded to produce the various proteins that our
cells use to function; (see Fig. 4, p. 22).
In cancer, chromosomes sometimes break and recombine
causing large-scale changes within the genome. Genes can
also be altered by single mutations in DNA units. Over the
years, researchers have determined that cancer-associated
genetic mutations are often found in one of two classes of
genes: oncogenes and tumor suppressor genes. Oncogenes
can drive the initiation and progression of cancer by
producing abnormal proteins that permit cancer cells to
ignore normal proliferative regulatory signals. Tumor
suppressor genes encode proteins that normally stop the
emergence of cancer. Mutations in these genes result in
proteins that fail to function properly, enabling cancer cells to
proliferate unchecked.
The correlation of genetic mutations with specific
malfunctions of cellular molecular machinery that result in
cancerous cell behaviors has provided the impetus for the
development of many molecularly targeted cancer drugs,
bringing the prospects of a new day for cancer prevention,
detection, diagnosis and treatment closer to reality.
