Module 2.1: The Pathology Of Cancer

Question 1

Cancer

Answer 1

Abnormal cell population that:
- divide uncontrollably
- Invade and potentially spread to other tissues

Question 2

Neoplasm

Answer 2

any abnormal tissue that forms when cells grow and divide more than should or don’t die when meant to
can be harmless growth, or cancerous

Question 2

Tumor

Answer 2

non specific term for neoplasm
means ‘Mass’, any swelling or abnormal enlargement

Question 3

Benign Tumours

Answer 3

• non cancerous
• can’t invade or spread
• can attain size of 50 kilograms or more without killing patient
• appearance is smooth and round contour which reminiscent of a sea sponge

Question 4

Malignant Tumour

Answer 4

• cancerous
• can invade into other tissues. This spreading is known as metastasis
• can spread and kill before even reaches 50 kilograms
• have spiky contour reminiscent of a crab

Question 5

Metastasis

Answer 5

process of malignant neoplasm invading other tissues
difficult to control and major mechanism of cancer that kills patients
Invasion commonly happens first, eventually spreading through bloodstream to colonize

Question 6

Carcinoma

Answer 6

Type of cancer that affects epithelial cells (skin, blood vessels, urinary tract and organs)

Question 7

Sarcoma

Answer 7

cancer begins in tissues that support and connect to the body
develop in fat, muscles, nerves, tendons, joints, blood vessels, lymph vessels, cartilage or bone

Question 8

Lymphoma

Answer 8

cancer in the lymphocytes (infection fighting cells of immune system, found in glands, nodes and lymphoid tissue)

Question 9

Glioma

Answer 9

tumours arise from connective tissues of the brain

Question 10

Leukemia

Answer 10

cancer of blood and bone marrow cells. Occurs when healthy blood cells change and grow uncontrollably

Question 11

Etiology of Cancer

Answer 11

caused by genetic mutations
cancer risk proportional to the likelihood of mutation occuring

Question 12

Impact of Cancer on First Nations People

Answer 12

Incidence: Higher cancer rates overall, especially colorectal cancer, across all age groups and sexes.
Prevalence: Most common cancers are female breast, male prostate, and colorectal cancer.
Mortality: Higher death rates for most cancers, including colorectal cancer. Exception: lower leukemia mortality in First Nations males.
Survival: Lower five-year survival rates — 43% for males and 49% for females, compared to 54% and 60% in non-First Nations populations.

Question 13

Cancer Risk Factors: Tobacco

Answer 13

Tobacco is carcinogenic
Tobacco Smoke & Injury: Inhaled tobacco smoke contains toxic chemicals that kill epithelial cells in the airway and lungs.
Repair Mechanism: Stem cells at the injury site activate to repair damage through rapid cell division. Once repair is complete, stem cells return to a resting state.
Cancer Risk: Chronic injury (e.g., from smoking) can cause repeated stem cell activation, increasing the risk of mutations that lead to cancer.
Concept: Chronic injury and repair cycles, like those caused by smoking, may result in cancer. “Cancer is a wound that does not heal.”

Question 14

Cancer is a Genetic Disease

Answer 14

carcinogen or risk factors lead to genetic changes.
A genetic diseases is a disorder caused by a mutation in genes, chromosomal damages or a combination of mutations and environmental risk factors

Question 15

Environmental Risk Factors: UV Radiation

Answer 15

Risk Factor
Damage from ultraviolet (U V) radiation is cumulative; the risk for developing cancer increases over
time with continued direct exposure to the sun.
Damage
Exposure to U V radiation from the sun increases the risk of sustaining damage to the genome of
normal cells.
Cancer
When enough damage or mutations accumulate within a cell, the cell typically dies. However, in some
cases this build up of mutations provides selective growth advantages to the cells, making them more
likely to thrive and to continue dividing. This is how most cancers begin

Question 16

Variation in Cancer Risk

Answer 16

Certain tissues more susceptible to becoming cancerous because higher rate if stem cell divisions.
Lung Cancer: 6.8%
Liver Cancer: 0.6%
Brain Cancer: 0.6%
Thyroid Cancer: 1.3%

Question 17

Silent Mutation

Answer 17

change in DNA sequence that does not change amino acid sequence or protein product

Question 18

Oncogenic Mutation

Answer 18

Mutation that directly contributes to development of cancer

Question 19

Cancer Evolution

Answer 19

Transformation: A normal cell acquires genetic changes and becomes a tumour cell that divides faster than normal cells.

Progression: Tumour cells accumulate more mutations over time, creating genetically different variants (subclones) from the original cell.

Proliferation: Continued cell division leads to new mutations, giving some cells a growth advantage.

Tumour Heterogeneity: Tumours become genetically diverse, with many subclones that may differ in traits like invasiveness, metastasis, and drug resistance.

Question 20

Challenges to Treatment

Answer 20

Tissues Types: various types respond differently to treatments
Continuous Mutations: tumours can be heterogeneous as they contain genetically different subclones. Each
subclone may differ in its ability to metastasize, and response to cancer drugs. Not all of the cells that make up a tumour will respond to a specific
drug
Diversity: not two tumours re alike

Question 21

Oncogenes

Answer 21

Oncogenes are mutated versions of proto-oncogenes that produce proteins with altered functions, giving cancer cells a growth advantage. These genes typically regulate growth factor receptor pathways involved in processes like embryonic development, homeostasis, and injury repair. A mutation in just one allele can trigger cancer-promoting effects. Oncogenes are most often linked to sporadic (non-inherited) cancers.

Question 22

Tumour Suppressor Gene: TP53

Answer 22

TP53 is mutated in some capacity in nearly all cancers. The protein product of T P53 is known as p53 and
regulates cell division.

Question 22

Tumour Suppressor Genes

Answer 22

Tumor suppressor genes help prevent cancer by regulating uncontrolled cell growth and promoting cell death. They act as checkpoints in the cell cycle and are involved in developmental processes that require controlled apoptosis. For tumor suppressor genes to contribute to cancer progression, both alleles must be mutated. These mutations are frequently seen in familial (inherited) cancers.

Question 23

Protein P53

Answer 23

p53’s most prominent role is to respond to genomic damage by activating repair and/or cell death programs. This function prevents cells with cancer-causing mutations from surviving. In other words, p53 puts the “brakes” on cells so they don’t divide too quickly. In contrast, p53-deficient cells can tolerate or even thrive with oncogenic mutations, providing them with a selective advantage over cells with p53 intact. In G1 and S checkpoint

Question 24

Mechanism of P53 Activity

Answer 24

Activation of p53: DNA damage leads to the activation and accumulation of normal p53. p53 binds to specific DNA sequences, causing: Cell cycle arrest in G1. Induction of DNA repair through upregulation of repair genes. DNA Repair: Proteins activated by p53 attempt to repair DNA mutations. If repair is successful, the cell proceeds through the cell cycle. If repair fails, p53 triggers: Apoptosis (programmed cell death) or Senescence (permanent cell cycle arrest). Inactive p53: In cells with mutated or lost TP53: DNA damage does not lead to p53 activation or DNA binding. No cell cycle arrest or DNA repair occurs. Damaged cells can continue proliferating, leading to the potential development of malignant tumors.

Question 25

Oncogenes: ERBB-1

Answer 25

The E R B B-1 gene codes for the protein Epidermal Growth Factor Receptor (E G F R). gene was affected in over 25% of glioblastoma cases and nearly 15% of lung adenocarcinomas

Question 26

Epidermal Growth Factor Receptor (E G F R)

Answer 26

E G F R detects extracellular signals, or ligands, and forms dimers in order to transmit that signal into the cell. E G F R kicks off a large number of processes associated with cell growth and survival. This signal is tightly regulated in normal cells to avoid unwanted proliferation.

Question 27

Gene Expression Through EGFR

Answer 27

EGFR (Epidermal Growth Factor Receptor) Mechanism of Action: Ligand Binding: When an extracellular ligand binds to EGFR, it induces a structural change in the receptor's intracellular domains. This structural change activates the receptor. Phosphorylation: The activation of EGFR leads to its phosphorylation in the cytoplasm. Secondary messengers are also phosphorylated by the active EGFR. These activated messengers transmit the signal to the nucleus. Gene Expression: The signal in the nucleus increases the transcription of genes involved in: Cell proliferation and survival. Cell migration and angiogenesis (formation of new blood vessels). Termination: Termination of the EGFR signal is essential to prevent excessive or unwanted proliferation. The response is terminated by: Ligand release. Receptor degradation.

Question 28

Oncogenic Activation of EGFR

Answer 28

1. Hyperactivation of EGFR Mechanism: EGFR receptor activity is drastically increased with the same amount of ligand binding. Effect: More secondary messengers are activated, amplifying the signal sent to the nucleus. Outcome: Promotes pro-cancer processes: Angiogenesis Cell proliferation Inhibition of apoptosis Migration, adhesion, and invasion 2. Constitutive Activation of EGFR Cause: Other mutations in ERBB-1 cause EGFR to signal without any ligand (no external stimulus). Mechanism: EGFR is always active, as there’s no signal termination. Effect: The pro-cancerous processes (e.g., angiogenesis, proliferation, etc.) remain active constantly. Outcome: Continuous activation of cancer-promoting pathways.