area (e.g., tongue, skin of face), then the tumor will be detected early. If the site of
origin is in a hidden area (e.g., ovaries), then the tumor may grow undetected and be
diagnosed only when metastatic spread produces secondary tumorsin other more easily
detected anatomical regions. The primary tumor may produce symptoms by virtue of
its location (primary brain tumor causing seizures) or by means of its erosive, infiltra-
tive behavior (pulmonary adenocarcinoma eroding a blood vessel, causing bleeding into
the lung and hemoptysis[coughing up blood]). Alternatively, symptoms may arise from
the secondary metastatic tumors being present in vital organs such as brain or liver.
Metastases to bone are common and can cause the bone to break (pathological frac-
tures) or can cause severe pain. It is possible for a pea-sized primary tumor to give rise
to hundreds of secondary tumors ranging in size from golf-ball dimensions to very
small tumors that can be seen only with a microscope (“micromets”).
The process of metastasis usually occurs when the cancerous cells are spread either
through the bloodstream or via the lymphatic system. Carcinomas are more frequently
spread by the lymphatic system, while sarcomas typically are disseminated by emboliza-
tion through blood vessels; however, either tumor type can be spread by either mode of
dissemination. The spread of a breast carcinoma through the lymphatic system to the
lymph nodes of the axilla (“armpit”) is a well-recognized mode of spread. Organs that
receive a voluminous blood supply are frequent sites for blood-borne metastatic spread
for either carcinomas or sarcomas. Understandably, secondary tumors are thus common
in the liver, lungs, and brain. When a primary tumor has produced many secondary metas-
tases, the overall tumor burden is high, and the afflicted individual experiences weight
loss and wasting (producing the phenomenon referred to as cachexia). Alternatively,
tumors can produce widespread effects on the host through the aberrant synthesis of hor-
mones or other chemical factors that influence brain or bone marrow function; such sys-
temic chemical effects are referred to as paraneoplatic syndromes. An example of such a
syndrome occurs when carcinomas of the lung produce the hormone ACTH.
Understanding the diverse clinical phenomenology of cancer at a molecular level is
challenging. Cancer is a fundamental disease of cells and of the macromolecular con-
stituents of cells. Since cancer is characterized by an alteration in the control mecha-
nisms that govern cell proliferation and differentiation, the nucleic acids (DNA, RNA)
are the central players in the molecular cascade of cancer. A wealth of data support
the key role played by the nucleic acids. Ever since Sir Percival Pott’s recognition of
environmentally induced scrotal cancer in chimney sweeps (in 1775!), the importance of
chemical carcinogenesis has been appreciated. Prototypic chemical carcinogens include
polycyclic aromatic hydrocarbons and aromatic amines that intercalate into nucleic
acids, thereby altering the conformation and function of DNA and RNA. Carcinogenic
nitrosamines are transformed into reagents that donate methyl and ethyl groups to RNA
and DNA. Carcinogenic metals such as beryllium and cadmium participate in electrophilic
reactions with the basic nitrogen atoms contained within RNA and DNA.
Recognizing that nucleic acids constitute the clinical–molecular interface in cancer
represents a major challenge in drug design. Nucleic acids are crucial not only to the
growth of the tumor but also to the overall wellbeing of the patient in general. The
tumor grows in an independent manner that is not controlled or regulated by the usu-
ally operative control mechanisms in the body; in this way, the tumor is behaving like
a “nonself ” exogenous parasite. However, unlike an exogenous parasite, the tumor is in
fact an endogenous structure composed of the exact same molecules and building
ENDOGENOUS CELLULAR STRUCTURES 461