Biology of Cancer

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Questions and Answers

What is the main reason why pancreatic and ovarian cancers have a higher percentage of fatalities compared to breast and prostate cancers?

They have a higher incidence rate

The cancers are more aggressive and spread faster

Fewer treatment options are available for these cancers

They are often diagnosed at a later stage (correct)

What is the primary mechanism by which viruses contribute to the development of cancer?

By inducing genomic instability

By inducing apoptosis in infected cells

By inserting viral DNA into the host genome (correct)

By activating growth suppressors

What is the term for the process by which cancer cells develop a blood supply?

Metastasis

Invasion

Apoptosis

Angiogenesis (correct)

Which of the following is NOT a hallmark of cancer?

Inducing immune destruction Signup and view all the answers

What is the term for the genetic changes that occur in cancer cells that affect gene expression or function?

Mutations Signup and view all the answers

What is the primary mechanism by which radiation contributes to the development of cancer?

Increasing cell turnover and injury Signup and view all the answers

What is the term for the process by which cancer cells resist programmed cell death?

Resisting cell death Signup and view all the answers

What is the term for the process by which cancer cells develop the ability to multiply indefinitely?

Enabling replicative immortality Signup and view all the answers

What is the primary function of the p53 gene?

To act as a 'guardian of the genome', detecting genomic damage Signup and view all the answers

What is a characteristic of cancer cells?

They do not exhibit contact inhibition and can grow uncontrollably Signup and view all the answers

What is the result of inactivating tumor suppressor genes in cancer cells?

Increased HIF-1α and increased angiogenesis Signup and view all the answers

What is the role of VEGF in cancer?

It is a vascular endothelial growth factor that promotes angiogenesis Signup and view all the answers

What is the result of increased HIF-1α in cancer cells?

Increased resistance to chemotherapy Signup and view all the answers

What is the function of angiogenesis inhibitors in normal tissue?

To bind to cellular surface receptors and decrease vessel growth Signup and view all the answers

What is the role of p53 in the intrinsic apoptosis pathway?

It is an activator of apoptosis Signup and view all the answers

What is the result of p53 suppression in cancer cells?

Decreased apoptosis and increased angiogenesis Signup and view all the answers

What is the hallmark of inducing angiogenesis in cancer?

Establishing new blood vessels and promoting vascularization Signup and view all the answers

What is the role of Li-Fraumeni syndrome in cancer?

It is a familial cancer syndrome caused by a mutation in the p53 gene Signup and view all the answers

What is the primary function of the G1 checkpoint in the cell cycle?

To verify that DNA is undamaged and resources are available Signup and view all the answers

What is the result of the t(9;22) translocation in chronic myeloid leukemia (CML)?

A BCR-ABL fusion protein that promotes growth of myeloid cells Signup and view all the answers

What is the role of proto-oncogenes in normal cell proliferation?

To encode components of pathways that regulate normal cell proliferation Signup and view all the answers

What is the function of the M checkpoint in the cell cycle?

To ensure that sister chromatids are attached to mitotic spindles Signup and view all the answers

What is the effect of the HER2/neu gene overexpression in breast cancer?

Hyper-responsiveness to growth factors Signup and view all the answers

What is the role of the Rb tumor suppressor gene in normal cell proliferation?

To monitor anti-growth cellular signals and block activation of the growth/division phase Signup and view all the answers

What is the result of the t(8;14) translocation in Burkitt Lymphoma?

An excess production of a proliferative factor Signup and view all the answers

What is the effect of the BCR-ABL fusion protein in chronic myeloid leukemia (CML)?

Promotion of growth of myeloid cells Signup and view all the answers

What is the primary function of oncogenes in cancer cells?

To promote cell growth and division independent of normal regulatory mechanisms Signup and view all the answers

What is the effect of the Rb gene mutation in retinoblastoma?

Less regulation of cell growth Signup and view all the answers

What is the primary mechanism by which immune cells like cytotoxic T cells and NK cells contribute to cancer treatment?

By activating the intrinsic pathway for apoptosis Signup and view all the answers

What is the primary limitation of using tumor markers for cancer diagnosis?

They are not useful for screening healthy individuals Signup and view all the answers

What is the primary advantage of using surgery as a cancer treatment?

It allows for the relief of symptoms caused by tumor obstruction Signup and view all the answers

What is the primary goal of cancer treatment using a combination of drugs?

To target the hallmarks of cancer Signup and view all the answers

What is the primary mechanism of action of radiation therapy in cancer treatment?

It targets rapidly dividing cells, including cancer cells and normal cells Signup and view all the answers

What is the key characteristic that distinguishes a malignant tumor from a benign tumor?

Invasion of normal tissue Signup and view all the answers

What is the primary advantage of using chemotherapy in combination with other drugs?

It allows for the targeting of multiple weaknesses in cancer cells Signup and view all the answers

What is the term for the formation or presence of a new, abnormal growth of tissue?

Neoplasm Signup and view all the answers

What is the primary goal of immunotherapy in cancer treatment?

To change the immune response to cancer cells from protective to destructive Signup and view all the answers

What is the term for a benign tumor that arises from fat cells?

Lipoma Signup and view all the answers

What is the primary advantage of targeted cancer therapy?

It targets specific growth characteristics of a class of tumor Signup and view all the answers

What is the term for a premalignant condition characterized by abnormal growth and cellular atypia?

Dysplasia Signup and view all the answers

What is the primary role of molecular and genetic analyses in cancer treatment?

To classify the spectrum of mutations underlying a specific cancer phenotype Signup and view all the answers

What is the primary limitation of using chemotherapy as a cancer treatment?

It is not effective for cancer cells that are resistant to chemotherapy Signup and view all the answers

What is the term for the study of the functions and interactions of all the genes in the genome?

Genomics Signup and view all the answers

What is the primary mechanism of action of monoclonal antibodies in cancer treatment?

They target unique antigens on cancer cells and induce apoptosis Signup and view all the answers

What is the term for a malignant tumor that arises from epithelial tissues?

Carcinoma Signup and view all the answers

What is the term for a preinvasive epithelial tumor that is localized to the epithelium and has not penetrated the local basement membrane?

Carcinoma in situ Signup and view all the answers

What is the term for the process by which cancer cells develop increased vascularity?

Angiogenesis Signup and view all the answers

What is the term for a benign tumor that arises from uterine smooth muscle?

Leiomyoma Signup and view all the answers

What is the primary difference between genetics and genomics?

Genomics includes both germ cell and somatic cell mutations, as well as genetic interactions. Signup and view all the answers

What is the main characteristic of sporadic cancers?

They involve genetic changes in somatic cells. Signup and view all the answers

What is the purpose of a family pedigree in identifying hereditary cancer?

To identify which gene to test for and whom to consider testing. Signup and view all the answers

What is the significance of BRCA1 and BRCA2 genes in hereditary breast cancer?

They are tumor suppressor genes that regulate DNA repair. Signup and view all the answers

What is the typical lifetime risk of developing breast cancer for women with BRCA1 or BRCA2 mutations?

50-80% Signup and view all the answers

What is the role of PTEN gene in breast cancer?

It is a gene that increases the risk of breast cancer. Signup and view all the answers

What is the main difference between hereditary and familial cancers?

Hereditary cancers are caused by genetic mutations, while familial cancers are caused by environmental factors. Signup and view all the answers

What is the approximate increase in the risk of colorectal cancer for individuals with one affected first-degree relative?

2-3 times higher Signup and view all the answers

What is the main characteristic of autosomal dominant mutations?

One parent must have the disorder. Signup and view all the answers

What is the purpose of genetic counseling and testing in hereditary cancer?

To identify individuals at high risk of cancer and provide preventive measures. Signup and view all the answers

What is the primary function of the APC gene related to cancer?

Tumor suppressor Signup and view all the answers

What is the result of inactivating the BRCA tumor suppressor gene?

The repair of damaged DNA is impaired. Signup and view all the answers

What is the approximate lifetime risk of colorectal cancer for individuals with Hereditary Nonpolyposis Colorectal Cancer (HNPCC)?

80% Signup and view all the answers

What is the purpose of predictive genetic testing in the context of cancer?

To identify inherited gene mutations that increase cancer risk Signup and view all the answers

What is the mode of inheritance of Hereditary Nonpolyposis Colorectal Cancer (HNPCC)?

Autosomal Dominant Signup and view all the answers

What is the percentage of colorectal tumors that have an APC mutation?

85% Signup and view all the answers

What is the primary role of a genetic counselor in the context of cancer risk?

To evaluate family history and counsel on risk and management Signup and view all the answers

What is the name of the criteria used to identify patients with Hereditary Nonpolyposis Colorectal Cancer (HNPCC)?

Both A and B Signup and view all the answers

Study Notes

Cancer Incidence in the US

Pancreas and ovary have a lower incidence of cancer, but a higher percentage of those who develop these cancers die
Breast and prostate cancers are more survivable than lung and bronchus cancers

What is Cancer?

A disease caused by an uncontrolled division of abnormal cells in a part of the body

Inheritance of Cancer

Heritable cancer syndromes exist, but the majority of cancers are not familial
Cancer is a genetic disease, but most mutations that lead to cancer are somatic (occur in body cells, not germ cells)

Hallmarks of Cancer

8 Hallmarks and 2 traits that enable cancer progression:
- Avoiding immune destruction
- Sustaining proliferative signaling
- Deregulating cellular energetics
- Resisting cell death
- Inducing angiogenesis
- Genomic instability (mutator phenotype)
- Activating invasion and metastasis
- Tumor-promoting inflammation
- Enabling replicative immortality
- Evading growth suppressors

Genetic Changes in Cancer

Mutations: DNA alterations that affect expression or function of a gene
Epigenetic effects: DNA methylation, histone acetylation, altered expression of non-coding RNA
Causes of genetic mutations:
- Viruses (e.g. HPV increases risk of cervical cancer)
- Bacteria (e.g. chronic H. pylori increases risk of gastric adenocarcinoma)
- Chemicals (e.g. smoking increases risk of lung cancer)
- Radiation (e.g. UV and ionizing radiation increase risk of skin cancer)

Multiple Hits Lead to Cancer

Exposure, infection, or mutation can render a "hit" that increases the risk of cancer
One or two "hits" can leave a cell more prone to mutation and cancer development

Hallmark: Sustained Proliferative Signaling

Cancer cells do not obey or require normal signals for cell division
Proto-oncogenes: genes that encode components of pathways that regulate normal cell proliferation
Mutated proto-oncogenes (oncogenes) can lead to checkpoint dysfunction

Cell Division

Checkpoints: G1, S, and M (in Metaphase)
G1 checkpoint: cell checks for DNA damage and resource availability
S checkpoint: cell checks for DNA errors
M checkpoint: cell checks for sister chromatid attachment

Hallmark: Evading Growth Suppressors

Tumor-suppressor genes: genes that monitor antigrowth cellular signals and block cell growth
Examples: Rb, p53
Mutations in tumor-suppressor genes can lead to persistent cell growth

Hallmark: Inducing Angiogenesis

Angiogenesis: the process of establishing new blood vessels
Angiogenic factors and inhibitors normally control vessel development
In cancer, angiogenesis is up-regulated, leading to increased blood supply

Hallmark: Resisting Cell Death

Apoptosis: programmed cell death
In cancer, apoptosis is disrupted, leading to uncontrolled cell growth
Two pathways to apoptosis: intrinsic and extrinsic

Tumor Markers

Substances produced by both benign and malignant cells
Examples: hormones, enzymes, genes, antigens, and antibodies
Useful for:
- Screening and identifying individuals at high risk for cancer
- Diagnosing specific types of tumors
- Following the clinical course of a tumor

Cancer Treatment

Surgery: allows for diagnosis and staging of disease, and can be used for prevention in high-risk groups
Radiation therapy: used to kill cancer cells while minimizing damage to normal structures
Chemotherapy: attacks rapidly dividing cells, often used in combination with other treatments
Immunotherapy: targets unique antigens on cancer cells or changes the immune response to a tumor
Targeted disruption of cancer: uses a combination of drugs to target specific hallmarks of cancer

Tissue Pathology of Cancer

Definitions:
- Neoplasm/Tumor: a new, abnormal growth of tissue
- Malignant: a tumor that tends to invade normal tissue or recur after removal
- Benign: a slow-growing tumor that is non-invasive and does not metastasize
Cancer: a malignant tumor

Cancer Classification

Based on:
- Tissue and organ of origin
- Extent of distribution (stages)
- Microscopic appearance of the malignant tumor
- Critical genetic changes in the cancer cells

Progression to Malignancy

Cancers develop incrementally as they accumulate genetic mutations
Careful surveillance can detect atypical cells or abnormal growth before it has progressed to malignancy

Genetics and Cancer

Genomics: the study of functions and interactions of all genes in the genome
Genomics vs Genetics:
- Genetics: applies to mutations that can be inherited
- Genomics: applies to germ cell mutations and somatic cell mutations, and interactions between genes and environment
All cancers involve genes:
- Critical cancer genes: oncogenes and tumor suppressor genes
- These genes regulate cell growth, division, differentiation, and death### Breast Cancer
Most common cancer in women
5-10% of breast cancer cases in the US are inherited
90% of breast cancer cases are not inherited
BRCA1 and BRCA2 are the genes associated with inherited breast cancer
Women with BRCA1 mutations have a 50-80% lifetime risk of developing breast cancer
Women with BRCA2 mutations have a 50-80% lifetime risk of developing breast cancer
BRCA1 also associated with 20-50% lifetime risk of ovarian cancer and moderate risk of colon and prostate cancer
BRCA2 also associated with 10-20% lifetime risk of ovarian cancer
Both BRCA1 and BRCA2 are tumor suppressor genes that code for proteins important in DNA damage repair
Mutations in BRCA1 and BRCA2 impair DNA repair, increasing cancer risk

Colorectal Cancer

Family history increases the risk of colorectal cancer
Risk of colorectal cancer in people with one affected first-degree relative is 2-3 times higher than the general population
Hereditary syndromes that increase the risk of colorectal cancer include Familial Adenomatous Polyposis (FAP) and Hereditary Nonpolyposis Colorectal Cancer (HNPCC)

Familial Adenomatous Polyposis (FAP)

Caused by a mutation in the APC gene, which encodes a tumor suppressor
Can occur sporadically in somatic cells, but inherited mutations lead to FAP
85% of colorectal tumors have an APC mutation

Hereditary Nonpolyposis Colorectal Cancer (HNPCC)

Also known as Lynch Syndrome
Caused by mutations in any of 6 genes involved in DNA repair
Affected individuals have an 80% lifetime risk of colorectal cancer
Autosomal dominant inheritance pattern
Increases risk of colon (80%), endometrial (60%), ovarian, stomach, small intestine, biliary tract, renal, and skin cancers

Genetic Testing for Cancer Risk

Predictive genetic testing looks for inherited gene mutations that increase cancer risk
May be suggested for individuals with a strong family history of certain cancers, a personal history of cancer, or family members of someone with an inherited gene mutation
Genetic counseling involves evaluating family history, creating a family pedigree, and counseling on risk and management of inherited cancer

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Description

This quiz covers cancer incidence in the US, types of cancer, inheritance of cancer, and what cancer is as a genetic disease.