Discoveries across the breadth of biomedical research, from
population science and basic research to translational and
clinical research, have led to our current comprehension
of how cancer arises and develops (see sidebar on What Is
Basic Research and How Does It Drive Progress against
Cancer?, p. 19).
We have learned that cancer is a collection of diseases that
arise due to uncontrolled cell multiplication. In adults, cell
multiplication is a highly controlled process that occurs
mostly to replenish cells that die due to normal wear and
tear or damage from external factors. If the processes that
control normal cell multiplication and lifespan go awry,
cells start multiplying uncontrollably, fail to die when
they should, and begin to accumulate. In body organs
and tissues, the accumulating cells form masses called
tumors, whereas in the blood or bone marrow they crowd
out normal cells. Over time, some cancer cells invade
local and distant tissues, a process termed metastasis,
by entering the bloodstream or lymphatics, and form
secondary tumors at remote sites. Most cancer-related
deaths are due to metastasis.
The normal behavior of each cell in the human body is
controlled by the genetic material within it. The genetic
material comprises chains of deoxyribonucleic (DNA)
units arranged in a particular order and packaged into
condensed structures called chromosomes, inside the cell’s
nucleus (see sidebar on Genetic and Epigenetic Control of
Cell Function, p. 20). The order of the DNA units as well
as its three-dimensional structure dictates which protein
and how much of it is made by each cell.
Alterations in the DNA sequence, referred to as mutations,
can disrupt normal protein function; they are the leading
cause of cancer development (see sidebar on Genetic
Mutations, p. 21). Cancer-associated mutations most
commonly affect three types of genes: oncogenes,
tumor suppressors, and DNA repair genes. Mutations in
oncogenes promote cell multiplication while mutations
in tumor suppressor and DNA repair genes directly
or indirectly release the normal brakes that keep cell
multiplication in check in healthy cells. Each person’s
cancer has a unique combination of mutations, and as
a cancer progresses, additional mutations accumulate.
The number of cells within a growing tumor that carry
a given mutation depends on when the mutation was
acquired during tumor growth. Thus, even within the
same tumor, different cancer cells often have different
genetic mutations. This variation, or heterogeneity, within
a tumor or between a primary and metastatic tumor is
a leading cause of resistance to treatment and thereby
Although 5 to 10 percent of cancer-causing mutations
can be inherited (see Table 3, p. 22), most are acquired
over an individual’s lifetime due to errors arising during
normal cell multiplication or as a result of environmental
• Research provides our understanding
of cancer biology, including its initiation,
development, and progression.
• Cancer is not one disease; it is a collection
of diseases characterized by the
uncontrolled growth of cells.
• Changes in the genetic material in a
normal cell underpin cancer initiation
and development in most cases.
• A cancer cell’s surroundings influence
disease development and progression.
• The most advanced stage of cancer, i.e.,
metastatic disease, accounts for most
• The more we know about the interplay
between the individual factors influencing
cancer biology, the more precisely we can
prevent and treat cancer.
In this section you will learn: