everyone. Why does cancer strike some
and not others?
Although once perceived as
disorganized cell growth, this disease is
now known to be a logical, coordinated
process in which a precise sequence of
changes a normal cell
When cells fail to follow normal
controls of cell division and multiply
excessively, an abnormal mass of
proliferating cells called a
o-plazm, “new growth”) results.
Neoplasms are classiﬁed as
benign neoplasm is strictly a local affair.
Its cells remain compacted, are often
encapsulated, tend to grow slowly, and
seldom kill their hosts if removed before
they compress vital organs.
In contrast, cancers are malignant
neoplasms, nonencapsulated masses that
grow relentlessly. Their cells resemble
immature cells, and they invade their
surroundings rather than pushing them
aside, as reﬂected in the name
from the Latin word for “crab.” Whereas
normal cells become fatally “homesick”
and die when they lose contact with the
surrounding matrix, malignant cells tend
to break away from the parent mass—the
primary tumor—and travel via blood or
lymph to other body organs, where they
secondary cancer masses
This capability for traveling to other
parts of the body, called
tah-sis), probably has a lot to
do with signaling molecules and the
cell-surface glycoproteins the cancer
cells bear. Metastasis and invasiveness
distinguish cancer cells from the cells of
benign neoplasms. Cancer cells consume
an exceptional amount of the body’s
nutrients, leading to weight loss and tissue
wasting that contribute to death.
Autopsies on individuals aged 50–70 who
died of another cause have revealed that
most of us have microscopic (but dormant)
in situ (conﬁned to origin site) neoplasms.
So what changes a normal cell into a
cancerous one? Some physical factors
(radiation, mechanical trauma), certain
viral infections, chronic inﬂammations, and
many chemicals (tobacco tars, saccharine,
some natural food chemicals).
All these factors cause
changes in DNA that alter the expression
of certain genes. However, not all
carcinogens do damage because most are
eliminated by peroxisomal or lysosomal
enzymes or by the immune system.
Furthermore, one mutation usually isn't
enough. It takes several genetic changes
to transform (convert) a normal cell into a
The discovery of
tumor), or cancer-causing genes,
in rapidly spreading cancers provided a
clue to the role of genes in cancer.
, benign forms of oncogenes
in normal cells, were discovered later.
Proto-oncogenes code for proteins that
are essential for cell division, growth, and
cellular adhesion, among other things.
Many proto-oncogenes have fragile sites
that break when exposed to carcinogens,
converting them to oncogenes. Failure to
code for certain proteins may lead to loss
of an enzyme that controls an important
metabolic process. Oncogenes may also
“switch on” dormant genes that allow
cells to become invasive and metastasize.
Known oncogenes now number over 100.
Oncogenes have been detected in
only 15–20% of human cancers, so
investigators were not too surprised by the
tumor suppressor genes
, which suppress cancer
by inactivating carcinogens, aiding DNA
repair, or enhancing the immune system’s
counterattack. In fact, over half of all
cancers involve malfunction or loss of just
2 of the 15 identiﬁed tumor suppressor
. This is not surprising
when you learn that
cells to make proteins that stop cell
division in stressed cells by promoting
apoptosis or cell cycle arrest.
Furthermore, although each type
of cancer is genetically distinct, human
cancers appear to share a master set of
genes—an activated group of 67 genes—
and almost all cancer cells have gained
or lost entire chromosomes. Whatever
genetic factors are at work, the “seeds”
of cancer appear to be in our own genes.
Cancer is an intimate enemy indeed.
Let’s look at the carcinogenesis
of colorectal cancer, one of the best-
understood human cancers. As with most
cancers, a metastasis develops gradually.
One of the ﬁrst signs is a polyp (see
photo on p. 146), a small benign growth
Cancer—The Intimate Enemy
consisting of apparently normal mucosa
cells. As cell division continues, the polyp
enlarges, becoming an adenoma (a term
for any neoplasm of glandular epithelium).
As various tumor suppressor genes are
inactivated and the
mobilized, the mutations pile up and the
adenoma becomes increasingly abnormal.
The ﬁnal consequence is colon carcinoma,
a form of cancer that metastasizes quickly.
Almost half of all Americans develop
cancer in their lifetime and a ﬁfth of us
will die of it. Cancer can arise from almost
any cell type, but the most common
cancers originate in the skin, lung, colon,
breast, and prostate. Although stomach
and colon cancer incidence is down,
skin and lymphoid cancer rates
Many cancers are preceded by
observable lumps or other structural
changes in tissue—for instance,
, white patches in the mouth
caused by the chronic irritation of ill-ﬁtting
dentures or heavy smoking. Although
these lesions sometimes progress to
cancer, in many cases they remain
stable or even revert to normal if the
environmental irritant is removed.
Diagnosis and Staging
Screening procedures are vital for
early detection. Examples include
(X-ray examination of the
breasts), examining breasts or testicles for
lumps, examining the blood for cancer
markers, and checking fecal samples for
Unfortunately, most cancers are
diagnosed only after symptoms have
already appeared. In this case diagnosis
is usually by
: removing a tissue
sample surgically and examining it
microscopically for malignant cells.
Increasingly, diagnosis includes chemical
or genetic analysis of the sample—typing
cancer cells by which genes are switched
on or off, a technique described below.
Physical and histological examinations,
lab tests, and imaging techniques (MRI,
CT) can determine the extent of the
disease (size of the neoplasm, degree
of metastasis, etc.). Then, the cancer is
from 1 to 4 according
to the probability of cure. Stage 1 has the
best probability of cure, stage 4 the worst.
C L O S E R