BIOLOGY OF CANCER
LECTURE 1. WHAT IS CANCER?
Cancer is a genetic disease:
Multi-step process where, due to genetic changes, normal cells are transformed into cancer
cells with increasing rate.
Darwinian evolution based on growth advantage
Benign versus malignant tumors: benign tumors
stay together in a closed environment (remain
localized at the site of their origin). Malignant
tumors invade the surrounding tissue and can
spread (metastasize).
A benign tumor always remains confined to its
original location, only when tumor cells grow into
the surrounding tissue, they are termed malignant.
Cancers originate from different type of tissues or cell types:
• Carcinoma from the epithelial tissue
o Adenocarcinoma: gland epithelium
o Squamous cell carcinoma: epithelium
• Sarcoma from the muscle tissue and connective tissue
• Leukemia from the hematopoietic system
• Gliomas from brain cells
• Melanoma from the pigment cells in the skin
The world’s most common types of cancer are the epithelial tumors of the lung, colon, breast, stomach
and cervix.
,Why are epithelial cancers most common?
1. Epithelial cells divide fast
2. Epithelial cells are exposed to the environment
3. Both are false
4. Both are true*
Most often cancer originates from 1 abnormal cell, when a
somatic mutation has occurred in a cell cancer can arise from
the accumulation of mutations over time.
Somatic mutations appear in normal cells of the body
translocations, carcinogenic substances, radiation and
viruses. See below
^^^ Inactivation of the same chromosome X results in
origination of a monoclonal cancer.
Example of a somatic mutation: translocation between chromosome 9
and 22 results in the Philadelphia chromosome.
Cancer arises from the accumulation of mutations over time. What is the
chance a person of 80 has cancer compared to a 20 year old person?
1. 15 fold
2. 150 fold*
The frequency of spontaneous mutations: 1 per gene per 105-106 cell divisions. The incidence of cancer
increases with age, which indicates the accumulation of cancer-causing mutations.
Cancers develop from less abnormal cells are for
example cervical cancer and colon cancer. Different
stages of cancer development: from normal
epithelium via low-grade to high-grade
intraepithelial neoplasm and ultimately carcinoma,
as depicted based on cervical cancer.
,Colon cancer arises from polyps (adenomas):
The process of the development is accelerated through:
• Consecutive cycles of mutations/selections
o Successive cycles of mutations ultimately lead to cancer.
• Increased genetic instability
o There are many changes in cancer cells on a chromosomal level. Chromosomal
instability and changes in a total number of chromosomes are frequently observed in
cancers.
• Decreased cell death (apoptosis) and
differentiation
o Apoptosis: a process of
programmed cell death, play an
important role in embryogenesis
and removal of old epithelial cells
and activated immune cells.
• Increased proliferation
o Polyp formation in the gut is mainly a
consequence of increased proliferation in
the intestinal epithelium.
• Independence from the environment
(metastasizing)
o Major reason why people die of cancer.
Successive cycles of mutations ultimately lead to cancer.
Genetic and epigenetic inactivation of genes: inactivation mutation,
histone modification (histones are differently acetylated, which leads
to different expression of the gene), DNA methylation (promotor is
, not binding anymore, therefore the product is not
made anymore). These are various ways in which
gene expression can be switched off: genetic and
epigenetic
Epigenetic mechanisms >>>>
Not all mutations are vital,
therefore you need a lot of
mutations. They need to
be in the right place and in
the right order to develop
a cancer.
The cancers may arise
from cancer stem cells.
This is done by tumor
initiating cells. A normal
stem cell can renew itself,
due to mutations in the
stem cell or the cell that is made a cancer stem cell is made which will
lead to tumors.
Increased cell division and decreased apoptosis
change the homeostasis and can thus
contribute to tumorigenesis.
Formation of metastasis: crossing the stroma à
vascular growth is required. The metastasis is a few-
stage process, in which tumor cells need to be
decoupled from their environment.
LECTURE 1. WHAT IS CANCER?
Cancer is a genetic disease:
Multi-step process where, due to genetic changes, normal cells are transformed into cancer
cells with increasing rate.
Darwinian evolution based on growth advantage
Benign versus malignant tumors: benign tumors
stay together in a closed environment (remain
localized at the site of their origin). Malignant
tumors invade the surrounding tissue and can
spread (metastasize).
A benign tumor always remains confined to its
original location, only when tumor cells grow into
the surrounding tissue, they are termed malignant.
Cancers originate from different type of tissues or cell types:
• Carcinoma from the epithelial tissue
o Adenocarcinoma: gland epithelium
o Squamous cell carcinoma: epithelium
• Sarcoma from the muscle tissue and connective tissue
• Leukemia from the hematopoietic system
• Gliomas from brain cells
• Melanoma from the pigment cells in the skin
The world’s most common types of cancer are the epithelial tumors of the lung, colon, breast, stomach
and cervix.
,Why are epithelial cancers most common?
1. Epithelial cells divide fast
2. Epithelial cells are exposed to the environment
3. Both are false
4. Both are true*
Most often cancer originates from 1 abnormal cell, when a
somatic mutation has occurred in a cell cancer can arise from
the accumulation of mutations over time.
Somatic mutations appear in normal cells of the body
translocations, carcinogenic substances, radiation and
viruses. See below
^^^ Inactivation of the same chromosome X results in
origination of a monoclonal cancer.
Example of a somatic mutation: translocation between chromosome 9
and 22 results in the Philadelphia chromosome.
Cancer arises from the accumulation of mutations over time. What is the
chance a person of 80 has cancer compared to a 20 year old person?
1. 15 fold
2. 150 fold*
The frequency of spontaneous mutations: 1 per gene per 105-106 cell divisions. The incidence of cancer
increases with age, which indicates the accumulation of cancer-causing mutations.
Cancers develop from less abnormal cells are for
example cervical cancer and colon cancer. Different
stages of cancer development: from normal
epithelium via low-grade to high-grade
intraepithelial neoplasm and ultimately carcinoma,
as depicted based on cervical cancer.
,Colon cancer arises from polyps (adenomas):
The process of the development is accelerated through:
• Consecutive cycles of mutations/selections
o Successive cycles of mutations ultimately lead to cancer.
• Increased genetic instability
o There are many changes in cancer cells on a chromosomal level. Chromosomal
instability and changes in a total number of chromosomes are frequently observed in
cancers.
• Decreased cell death (apoptosis) and
differentiation
o Apoptosis: a process of
programmed cell death, play an
important role in embryogenesis
and removal of old epithelial cells
and activated immune cells.
• Increased proliferation
o Polyp formation in the gut is mainly a
consequence of increased proliferation in
the intestinal epithelium.
• Independence from the environment
(metastasizing)
o Major reason why people die of cancer.
Successive cycles of mutations ultimately lead to cancer.
Genetic and epigenetic inactivation of genes: inactivation mutation,
histone modification (histones are differently acetylated, which leads
to different expression of the gene), DNA methylation (promotor is
, not binding anymore, therefore the product is not
made anymore). These are various ways in which
gene expression can be switched off: genetic and
epigenetic
Epigenetic mechanisms >>>>
Not all mutations are vital,
therefore you need a lot of
mutations. They need to
be in the right place and in
the right order to develop
a cancer.
The cancers may arise
from cancer stem cells.
This is done by tumor
initiating cells. A normal
stem cell can renew itself,
due to mutations in the
stem cell or the cell that is made a cancer stem cell is made which will
lead to tumors.
Increased cell division and decreased apoptosis
change the homeostasis and can thus
contribute to tumorigenesis.
Formation of metastasis: crossing the stroma à
vascular growth is required. The metastasis is a few-
stage process, in which tumor cells need to be
decoupled from their environment.
