Chapter 1: Molecular biology of Cancer
Definitions of keywords
Incidence
The incidence of cancer is defined to be the number of new cases that is registered within a
certain period (mostly 1 year). To be able to follow the incidence in time, or to enable
comparison between regions, the incidence is mostly expressed as the number of new cases
per 100.000 inhabitants/persons each year: the crude incidence rate.
Prevalence
The prevalence of cancer comprises all persons who somewhere in time have been
diagnosed with cancer; and are still living at a certain date. Hence, this is a diverse group,
ranging from persons who have been cured from cancer in the past to persons who just
have been diagnosed with cancer. The period can be unlimited, but also defined. As an
example: the 5-year prevalence on January 1st, 2010, comprises all still living people who
have been diagnosed with cancer during the previous 5 years.
Mortality
The mortality of cancer comprises the number of patients who died as a result of cancer
within a certain period (mostly 1 year).
Survival
Survival is the percentage of patients still living at a certain period after diagnosis. The
presented survival is a relative survival that approaches the “cancer-specific survival”. This
means that the survival observed is corrected for the expected death within a comparable
population (with respect to country/region, gender, age, and calendar year).
Cancer
What is the clinical definition of cancer?
Cancer is a group of diseases. More than 100 cancer types can be distinguished, and every
tumor is different. It is characterized by uncontrolled cell growth, which is usually invasive of
other tissues and can form metastases.
Does a patient with a tumor always have cancer?
No, a tumor is a mass of cells. However, not every tumor is invasive and metastasizing.
Benign tumors are not cancer, only malignant tumors are.
Why is a malignant tumor life threatening?
Malignant tumors can invade organs, which disturbs the organ function. The cancer cells
compete with normal cells for nutrients and oxygen. Growing tumors can also cause
obstructions.
What is the difference between certain tumors?
- Carcinomas: arise from epithelia (about 85% of all cancers)
- Adenocarcinomas: arise from glandular tissues (e.g., breast)
- Sarcomas: arise from mesodermal tissue (e.g., bone, muscle)
- Lymphomas: arise from (progenitors of) white blood cells
1
,Why is the incidence of carcinomas much higher?
Carcinomas are derived from epithelial cells. Epithelial cells are the cells that align our body
on the in- and outside. They are also the type of cell that are most exposed to carcinogens.
Cancer is a disease of the genome
What is a carcinogen?
A carcinogen is an agent causing cancer, as it causes alterations in the DNA of a cell. Cancer
cells contain many alterations in the DNA. The accumulation in the DNA of a cell causes
stepwise development of cancer (oncogenesis, carcinogenesis).
Is cancer inheritable?
No, almost all the mutations develop in somatic cells and will not be passed to the next
generation of offspring. However, some inherited germline mutations can increase the
chance to develop cancer and can be passed on to the next generation of offspring. These
mutations are rarely involved in causing cancer immediately.
Why does the risk to develop cancer increase at older age?
An accumulation of mutations in the DNA is needed for the development of cancer. It is
usually a matter of chance and time (exposure to carcinogens). The incidence of cancer is
increasing, due to the longer life expectancy.
The growth of a tumor
- Disturbed balance between proliferation, cell death
and differentiation
- Stimulation of proliferation, and loss of cell death and
differentiation
- Oncogenes and suppressor genes
2
, Characteristics of cancer cells
Is it possible to recognize cancer cells in tissue culture?
- Cancer cells have a different morphology
- Cancer cells can grow in low serum culture media
- Cancer cells show no/decreases contact inhibition
- Cancer cells can grow without substrate for attachment
How can oncogenes be identified in a laboratory
1. The gene is isolated from tumor cells.
2. Transfection of DNA into immortalized primary cells
3. Evaluation whether transfected cells obtain altered growth characteristics
Factors playing a role in the development of cancer
- Environment (soot, sunlight, asbestos)
- Diet (fruit, vegetables, fish) and exercise
- Alcohol (head and neck, breast)
- Smoking (>80 carcinogens; 40% of all cancer deaths)
- Reproduction, contraception, hormone replacement therapy
- Viruses (sexually transmittable)
- Own metabolism (by-products of metabolism and errors in DNA replication)
Treatment of cancer
The aim is to develop novel anti-cancer agents with selective activity against cancer cells,
thus causing less toxicity: targeted drugs. Therefore, we must learn about the differences
between tumor cells and normal cells.
The ‘conventional’ modalities of cancer treatment: basic principles
- Surgery
- Radiotherapy
- Chemotherapy
- Prevention of cell division (cytostatic effect)
- Killing of cancer cells (cytotoxic effect)
What are the limitations of conventional chemotherapy?
- Adverse events or toxicity on tissues
- The therapeutic index/window of most chemotherapeutics is relatively small
The therapeutic index/window is the difference between maximum tolerated dose (MTD)
and the minimum dose needed to exert anti-cancer activity.
What is the efficacy of current drugs?
Only a small proportion of patients benefits from treatment with the current drugs, because
tumors differ from each other. Genomics has shown that every tumor has its own unique
genetic profile. Different patients therefore need different treatments: ‘targeted therapy’ or
‘personalized medicine’.
3
Definitions of keywords
Incidence
The incidence of cancer is defined to be the number of new cases that is registered within a
certain period (mostly 1 year). To be able to follow the incidence in time, or to enable
comparison between regions, the incidence is mostly expressed as the number of new cases
per 100.000 inhabitants/persons each year: the crude incidence rate.
Prevalence
The prevalence of cancer comprises all persons who somewhere in time have been
diagnosed with cancer; and are still living at a certain date. Hence, this is a diverse group,
ranging from persons who have been cured from cancer in the past to persons who just
have been diagnosed with cancer. The period can be unlimited, but also defined. As an
example: the 5-year prevalence on January 1st, 2010, comprises all still living people who
have been diagnosed with cancer during the previous 5 years.
Mortality
The mortality of cancer comprises the number of patients who died as a result of cancer
within a certain period (mostly 1 year).
Survival
Survival is the percentage of patients still living at a certain period after diagnosis. The
presented survival is a relative survival that approaches the “cancer-specific survival”. This
means that the survival observed is corrected for the expected death within a comparable
population (with respect to country/region, gender, age, and calendar year).
Cancer
What is the clinical definition of cancer?
Cancer is a group of diseases. More than 100 cancer types can be distinguished, and every
tumor is different. It is characterized by uncontrolled cell growth, which is usually invasive of
other tissues and can form metastases.
Does a patient with a tumor always have cancer?
No, a tumor is a mass of cells. However, not every tumor is invasive and metastasizing.
Benign tumors are not cancer, only malignant tumors are.
Why is a malignant tumor life threatening?
Malignant tumors can invade organs, which disturbs the organ function. The cancer cells
compete with normal cells for nutrients and oxygen. Growing tumors can also cause
obstructions.
What is the difference between certain tumors?
- Carcinomas: arise from epithelia (about 85% of all cancers)
- Adenocarcinomas: arise from glandular tissues (e.g., breast)
- Sarcomas: arise from mesodermal tissue (e.g., bone, muscle)
- Lymphomas: arise from (progenitors of) white blood cells
1
,Why is the incidence of carcinomas much higher?
Carcinomas are derived from epithelial cells. Epithelial cells are the cells that align our body
on the in- and outside. They are also the type of cell that are most exposed to carcinogens.
Cancer is a disease of the genome
What is a carcinogen?
A carcinogen is an agent causing cancer, as it causes alterations in the DNA of a cell. Cancer
cells contain many alterations in the DNA. The accumulation in the DNA of a cell causes
stepwise development of cancer (oncogenesis, carcinogenesis).
Is cancer inheritable?
No, almost all the mutations develop in somatic cells and will not be passed to the next
generation of offspring. However, some inherited germline mutations can increase the
chance to develop cancer and can be passed on to the next generation of offspring. These
mutations are rarely involved in causing cancer immediately.
Why does the risk to develop cancer increase at older age?
An accumulation of mutations in the DNA is needed for the development of cancer. It is
usually a matter of chance and time (exposure to carcinogens). The incidence of cancer is
increasing, due to the longer life expectancy.
The growth of a tumor
- Disturbed balance between proliferation, cell death
and differentiation
- Stimulation of proliferation, and loss of cell death and
differentiation
- Oncogenes and suppressor genes
2
, Characteristics of cancer cells
Is it possible to recognize cancer cells in tissue culture?
- Cancer cells have a different morphology
- Cancer cells can grow in low serum culture media
- Cancer cells show no/decreases contact inhibition
- Cancer cells can grow without substrate for attachment
How can oncogenes be identified in a laboratory
1. The gene is isolated from tumor cells.
2. Transfection of DNA into immortalized primary cells
3. Evaluation whether transfected cells obtain altered growth characteristics
Factors playing a role in the development of cancer
- Environment (soot, sunlight, asbestos)
- Diet (fruit, vegetables, fish) and exercise
- Alcohol (head and neck, breast)
- Smoking (>80 carcinogens; 40% of all cancer deaths)
- Reproduction, contraception, hormone replacement therapy
- Viruses (sexually transmittable)
- Own metabolism (by-products of metabolism and errors in DNA replication)
Treatment of cancer
The aim is to develop novel anti-cancer agents with selective activity against cancer cells,
thus causing less toxicity: targeted drugs. Therefore, we must learn about the differences
between tumor cells and normal cells.
The ‘conventional’ modalities of cancer treatment: basic principles
- Surgery
- Radiotherapy
- Chemotherapy
- Prevention of cell division (cytostatic effect)
- Killing of cancer cells (cytotoxic effect)
What are the limitations of conventional chemotherapy?
- Adverse events or toxicity on tissues
- The therapeutic index/window of most chemotherapeutics is relatively small
The therapeutic index/window is the difference between maximum tolerated dose (MTD)
and the minimum dose needed to exert anti-cancer activity.
What is the efficacy of current drugs?
Only a small proportion of patients benefits from treatment with the current drugs, because
tumors differ from each other. Genomics has shown that every tumor has its own unique
genetic profile. Different patients therefore need different treatments: ‘targeted therapy’ or
‘personalized medicine’.
3
