Understanding the Biology of Cancer[1]
How does cancer develop?
For normal cells, the rate of cell division is carefully regulated so just enough cellsare produced to replace damaged cells and to provide cells needed for normal growth. Cancer begins when some cells escape from the normal controls on cell division, so too many cells are produced. To learn moreabout how cancers develop, read the first two sections of "Understanding Cancer" (i.e. the introduction through "Cancer as a Multistep Process"), available at
1.In situ or benign tumors can usually be treated successfully by surgical removal. In contrast,cancers (i.e. tumors which have become malignant) are much more dangerous and harder to treat. Explain why.
2.How does exposure to chemicals that cause mutations increase the risk of developing cancer?
Genes and Mutations that Contribute to the Development of Cancer
Proto-oncogenes code for proteins that contribute to normal stimulation of cell division needed for growth and repair. The different types of proteins are underlined in the flow chart below.
Growth factors bind to growth factor receptorsactivate series ofsignaling enzymes
activate protein transcription factors
increased transcription of genes that code for proteins that stimulate cell division
increased cell division = cell proliferation /
(Figure from
An oncogene is amutated proto-oncogenewhich codes for an abnormal protein that stimulates excessive cell division and thus can contribute to the formation of a tumor.
One type oftumor suppressor genecodes for proteins that inhibit cell division, e.g. by interfering with one of the proteins that stimulate cell division.If both copies of a tumor suppressor gene are mutated and code for inactive proteins, this eliminates one of the inhibitory controls oncell division, which can result inexcessive cell division and the formation of a tumor.
The development of an invasive or malignant cancer typically requires the accumulation ofat least five mutations in the same cell line, including:
- mutations of proto-oncogenes to oncogenes
- mutations oftumor suppressor genes so they code for inactive proteins
- other types of mutations that contribute to the variedabnormal characteristics of cancer cells.
3.Why do all of us need to have proto-oncogenes in the DNA of our cells? What would go wrong if our cells had mutated proto-oncogenes that coded for inactive proteins?
4.Match each type of gene in the first list with the type of mutation that would contribute to the development of cancer.
Proto-oncogene ___
Tumor suppressor gene ____
- Both copies of the gene are mutated so they code for inactive protein.
- The mutated gene codes for a protein that is more active than normal.
Explain your reasoning.
5. Some genes code for proteins that help to repair DNA when it has been damaged. Mutations to these genes can result in decreased effectiveness of DNA repair. Explain how reduced effectiveness of DNA repair can contribute to the development of cancer.
Different Types of Cancer
Different types of cancer all develop through the same basic biological processes. However,there are important differences between the types of cancer that develop in different parts of the body. For example:
- The characteristics that increase the risk ofcancer differ for different types of cancer.
- Different types of cancer have a different prognosis (measured as the proportion of patients still alive five years after diagnosis).
Type of Cancer / A Characteristic or Behavior that
Increases the Risk of This Type of Cancer / Prognosis
(Five-year survival)
Lung cancer / Smoking / 16%
Breast cancer / Inherited mutations in BRCA1 and BRCA2 genes / 86%
Melanoma* / Sunburns; high sun exposure during recreation and vacations / 91%
*Melanoma is the most dangerous type of skin cancer.
Cigarette smoke contains multiple cancer-causing chemicals which smokers typically inhale into their lungs. A pack-a-day smoker has about 10 times greater risk of lung cancer than a person who has never smoked. Cigarette smoking accounts for more than 80% of cases of lung cancer.
BRCA1 and BRCA2 genes contribute to DNA repair, and inherited mutations in these genes account for roughly 5% of breast cancers.
The UV radiation in sunlight can damagethe DNA in skin cells.
6.Explain how characteristics or behaviors as different as smoking, inherited mutations in BRCA1 and BRCA2, and intense sun exposure can all contribute to increased risk of cancer. What do all of these different risk factors have in common?
7.Explain why cigarette smoking increases the risk of lung cancer, but not melanoma, whereas intense sun exposure increases the risk of melanoma, but not lung cancer.
8. Explain how your behavior as a teenager (e.g. smoking or intense sun exposure) can affect whether you develop cancer decades later as a middle-aged adult
9.A study of breast cancer in a large sample of female twinsfound the following results.
Type of twin / For twins where at least one twin had breast cancer,% where both twins
had breast cancer / % where the other twin
did not have breast cancer
Identical or monozygotic
(have identical inherited genes) / 20% / 80%
Fraternal or dizygotic (only about half
their inherited genes are the same) / 12% / 88%
Based on these data, which of the following statements is true?
- Inherited genes are the main cause of breast cancer.
- Inherited genes contribute to the risk of breast cancer, but they are not the main cause.
- Inherited genes have no effect on the risk of breast cancer.
Explain how the evidence in the table supports your conclusion.
10.Explain the following statement: "Cancer is always a genetic disease, but cancer is usually not inherited".
11.Behaviors, environmental exposures and inherited genes all contribute to an increased risk of cancer, but to some extent the occurrence of cancer is random and unpredictable. For example, most women who have breast cancer in one breast do not have a second cancer in the other breast, even though both breasts have the same inherited genes, the same hormonal exposures, and usually the same environmental exposures. What is one likely reason why, in many women, a cancer develops in one breast, but not the other?
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[1]By Dr. Ingrid Waldron, Department of Biology, University of Pennsylvania, 2016.Teachers are encouraged to copy this Student Handout for classroom use. A Word file (which can be used to prepare a modified version if desired) andTeacher Notes are available at