Modern cancer therapy is multidisciplinary,

involving coordinated care by surgeons,

medical oncologists, radiation
oncologists,reconstructive surgeons,
pathologists, radiologists, andprimary care
physicians.
Understanding cancer biology is essential
to successfully implement personalized
cancer therapy.

 The following alterations are critical for

malignant cancer growth: self-sufficiency
of growth signals, insensitivity to growthinhibitory signals, evasion of apoptosis,
potential for limitless replication,
angiogenesis, invasion and metastasis.
Reprogramming of energy metabolism and
evading immune destruction.

EPIDEMIOLOGY
Basic Principles of Cancer Epidemiology
Epidemiologic studies that monitor
trends in cancer incidence and mortality
have tremendously enhanced our
understanding of the etiology of cancer.
Furthermore, analysis of trends in cancer
incidence and mortality allows us to
monitor the effects of different preventive
and screening measures, as well as the
evolution of therapies for specific cancers.

Cancer insidence and Mortaility in

the United States

Global Statistics on Cancer

Incidence
and Mortality

CANCER BIOLOGY
Hallmarks of Cancer
that there are six essential alterations in
cell physiology that dictate malignant
growth: self-sufficiency of growth signals,
insensitivity to growth-inhibitory signals,
evasion of apoptosis (programmed cell
death), potential for limitless replication,
angiogenesis, and invasion and metastasis

Cell Proliferation and

Transformation
In normal cells, cell growth and
proliferation are under strict control. In
cancer cells, cells become unresponsive to
normal growth controls, which leads to
uncontrolled growth and proliferation.
Human cells require several genetic
changes for neoplastic transformation.

Cancer Initiation
Tumorigenesis is proposed to have
three steps: initiation, promotion, and
progression.
Initiating events such as gain of
function of genes known as
oncogenes or loss of function of
genes known as tumor-suppressor
genes may lead a single cell to
acquire a distinct growth advantage.

 Cancer is thought to be a disease of

clonal progression as tumors arise from a
single cell and accumulate mutations
that confer on the tumor an increasingly
aggressive behavior. Most tumors go
through a progression from benign
lesions to in situ tumors to invasive
cancers (e.g., atypical ductal hyperplasia
to ductal carcinoma in situ to invasive
ductal carcinoma of thebreast).

Cell-Cycle Dysregulation in Cancer

The proliferative advantage of tumor
cells is a result of their ability to
bypass quiescence. Cancer cells
often show alterations in signal
transduction pathways that lead to
proliferation in response to external
signals.

 Mutations or alterations in the

expression of cell-cycle proteins, growth
factors, growth factor receptors,
intracellular signal transduction proteins,
and nuclear transcription factors all can
lead to disturbance of the basic
regulatory mechanisms that control the
cell cycle, allowing unregulated cell
growth and proliferation.

 The cell cycle is divided into four

phases (Fig. 10-6).During the
synthetic or S phase, the cell
generates a single copy of its genetic
material, whereas in the mitotic or M
phase, the cellular components are
partitioned between two daughter
cells.

The G1 and G2 phases represent gap

phases during which the cells
prepare themselves for completion of
the S and M phases, respectively.
When cells cease proliferation, they
exit the cell cycle and enter the
quiescent state referred to as G0.

Oncogenes
Normal cellular genes that contribute to
cancer when abnormal are called
oncogenes. The normal counterpart of
such a gene is referred to as a protooncogene.
Oncogenes may be growth factors (e.g.,
platelet-derived growth factor), growth
factor receptors (e.g., HER2), intracellular
signal transduction molecules (e.g., ras),

 Growth factors are ubiquitous

proteins that are produced and
secreted by cells locally and that
stimulate cell proliferation by binding
specific cell-surface receptors on the
same cells (autocrine stimulation) or
on neighboring cells (paracrine
stimulation).