Cancer is a disease of cells characterized by a shift in the
control mechanisms that govern cell proliferation and differentiation.
Cells that have undergone neoplastic transformation
often express normal fetal cell surface antigens or display other
signs of apparent immaturity. Cancer cells may also exhibit qualitative
or quantitative chromosomal abnormalities, including translocations
and amplified gene sequences. Cancer cells proliferate excessively
and form local tumors that can compress or invade adjacent normal
structures. Within local tumors, a small subpopulation of cells
can be described as tumor stem cells. These cells retain the ability
to undergo repeated cycles of proliferation and can migrate to distant
sites in the body to colonize various organs in the process called
metastasis. Thus, tumor stem cells can express clonogenic (colony-forming) capabilities.
Chromosomal abnormalities in tumor stem cells reflect their genetic
instability, which leads to progressive selection of subclones that
can survive more readily in the host’s multicellular environment.
Abnormalities in various metabolic pathways and cellular components
(e.g., expression of cell-surface drug transporters) accompany neoplastic
progression. The invasive and metastatic processes, as well as metabolic
abnormalities resulting from the cancer, cause illness and eventual
death unless the neoplasm can be eradicated with treatment.
A classification of anticancer drugs is presented in Figure 31–1.
Initial division is based on whether the drugs affect DNA (action
on DNA and action on mitotic spindle) or modulate hormonal activity
(hormonal agents). Drugs affecting DNA may inhibit synthesis or
directly damage DNA. As a group, anticancer drugs are more toxic
than any other drugs because they act not only on neoplastic cells
but also on normal cells that are in dividing or resting states.
Therefore, the benefits of anticancer drugs must be carefully weighed
against their risks.
Initial classification of anticancer drugs is based on
location(s) of action. The first two classes affect DNA or mitosis,
whereas the third class modulates hormonal influences on cancer
cells. Subsequent divisions of anticancer drugs affecting DNA are
based on whether the drug affects DNA directly, or alters DNA synthesis
and replication. Drugs that modulate hormonal influence on cancer
cells are subsequently divided into agonists or antagonists.
The incidence, geographic distribution, and behavior of specific
types of cancer are related to multiple factors, including gender,
age, genetic make-up, and exposure to environmental carcinogens.
Of these, environmental exposure is the only modifiable risk factor.
Chemical carcinogens, particularly those in tobacco smoke, as well
as azo dyes, aflatoxins, asbestos, and benzene have been clearly
implicated in cancer induction in humans and animals. In the laboratory,
potential environmental carcinogens can be identified by microbial
mutagenesis and animal testing.
Certain deoxyribonucleic acid (DNA) viruses and type C ribonucleic
acid (RNA) viruses have been implicated as cancer-causing (oncogenic)
agents in animals and humans. Oncogenic RNA viruses contain a reverse
transcriptase that transcribes the RNA of the tumor virus ...