Module 2.1: The Pathology Of Cancer Flashcards
Cancer
Abnormal cell population that:
- divide uncontrollably
- Invade and potentially spread to other tissues
Neoplasm
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
Tumor
non specific term for neoplasm
means ‘Mass’, any swelling or abnormal enlargement
Benign Tumours
- 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
Malignant Tumour
- 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
Metastasis
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
Carcinoma
Type of cancer that affects epithelial cells (skin, blood vessels, urinary tract and organs)
Sarcoma
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
Lymphoma
cancer in the lymphocytes (infection fighting cells of immune system, found in glands, nodes and lymphoid tissue)
Glioma
tumours arise from connective tissues of the brain
Leukemia
cancer of blood and bone marrow cells. Occurs when healthy blood cells change and grow uncontrollably
Etiology of Cancer
caused by genetic mutations
cancer risk proportional to the likelihood of mutation occuring
Impact of Cancer on First Nations People
see companion guide
Cancer Risk Factors: Tobacco
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.”
Cancer is a Genetic Disease
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
Environmental Risk Factors: UV Radiation
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
Variation in Cancer Risk
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%
Silent Mutation
change in DNA sequence that does not change amino acid sequence or protein product
Oncogenic Mutation
Mutation that directly contributes to development of cancer
Cancer Evolution: Transformation
normal cell has change in genetic code, becomes tumour cell, and divides more rapidly than unaffected cells
Cancer Evolution: Progression
Accumulation of mutations in daughter cells after tumour divides. Can be clone mutations or different, leading to variants.
Cancer Evolution: Proliferation
As cell proliferate, mutations of daughter cell can provide further growth advantages
Cancer Evolution: Tumour Heterogeneity
well-established
cancers can be quite heterogeneous - representing tens or hundreds of genetically different cancer
cells within the same tumour. Each variant and subclone may offer different physiological
characteristics (i.e., metastatic, invasive, drug resistant, etc.) to the tumour
Challenges to Treatment
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
Oncogenes
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.
Tumour Suppressor Gene: TP53
TP53 is mutated in some capacity in nearly all cancers. The protein product of T P53 is known as p53 and
regulates cell division.
Tumour Suppressor Genes
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.
Protein P53
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
Mechanism of P53 Activity
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.
Oncogenes: ERBB-1
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
Epidermal Growth Factor Receptor (E G F R)
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.
Gene Expression Through EGFR
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.
Oncogenic Activation of EGFR
- 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 - 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.
