Module 2.1 Flashcards
1
Q
cancer
A
- Cancer is the name given to a collection of related diseases.
- In all types of cancer, the body’s cells divide uncontrollably and spread to surrounding tissues.
- when enough damage or mutations accumulate within a cell, the cell usually dies. In some cases this build up of mutations provides selective growth advantages to the cells, making them more likely to thrive and continue dividing. This is how cancers begin.
2
Q
Cancer and Population Health
A
- Cancer poses a large and growing impact on the Canadian population and healthcare system
- Almost half of Canadians are expected to receive a diagnosis of cancer in their life.
- Age-standardized cancer mortality rates have decreased substantially since they peaked in 1988, cancer remains the leading cause of death among Canadians
- Cancer caused 29.6% of deaths in 2016
3
Q
Neoplasms
A
- defined as any abnormal tissue that forms when cells grow and divide more than they should, or when they don’t die when they should
- Can also refer to harmless growths of cells like skin tags, or cancerous growths
4
Q
Tumour
A
- specific term for a neoplasm. Means “mass” any swelling or abnormal enlargement in or on the human body may be called a tumour
- Can be harmless benign or cancerous malignant
5
Q
benign tumours
A
- cant invade or spread
- attain sizes of 50 kg or more without killing a patient
- smooth and round contours like a sea sponge
6
Q
malignant tumours
A
- Able to invade into other tissues. When they spread to other areas of the body, it is known as metastasis
- Can start to spread and may kill before they reach 50g. Considered a malignant neoplasm
- Have spiky contour like that of a crab
7
Q
Metastasis
A
- When cancers spread to other areas of the body, it is known as metastasis
- Troublesome characteristic of cancer, and one that remains difficult to control. Major mechanism by which cancers kill
- In adult cancers, invasion happens first. Eventually, the cancer can spread through the bloodstream and colonize distant sites
- Spread and may kill before they reach 50g
8
Q
Carcinoma
A
- type of cancer that affects epithelial cells. Usually form solid tumours
- Examples include prostate cancer, breast cancer, lung cancer and colorectal cancer
9
Q
Sarcoma
A
begin in tissues that support and connect the body. Can develop in fat, muscles, nerves, tendons, joints, blood vessels, lymph vessels, cartilage or bone.
10
Q
Lymphoma
A
type of cancer that begins in the lymphocytes
11
Q
Glioma
A
- tumours that arise from connective tissues of the brain
- Example of this is a glioblastoma
12
Q
Leukemia
A
cancer of blood and bone marrow cells. Occur when healthy blood cells change and grow uncontrollably
13
Q
What is the lifetime prevalence of cancer in Canada?
A
almost 50%
14
Q
what is cancer ultimately caused by?
A
genetic mutations and the risk is proportional to the likelihood of such mutations
15
Q
Incidence of cancer and first nations people
A
higher incidence of cancer cases compared to non First Nations peoples.
- Colorectal cancer is higher in First Nations populations of all age groups and for both sexes compared to other people in Ontario
16
Q
Prevalence of cancer and first nations people
A
- Most prevalent cancers among First Nations peoples are female breast cancer and male prostate cancer.
- The next most prevalent cancer type in First Nations was colorectal cancer.
17
Q
Mortality from cancer in relation to first nations people
A
- Mortality rate is significantly higher in First Nations peoples living in ontario compared to non First Nations peoples such as colorectal cancer.
- First Nations males have a lower mortality rate from leukemia than non First Nations males.
18
Q
survival of cancer in relation to first nations people
A
- 43% of First Nations males compared to 54% of the non-First Nations males and 49% of First Nations females compared to 60% of non-First Nations females survive 5 years or longer after their initial diagnosis.
19
Q
according to WHO how much of cancer is preventable
A
- 30-50% of cancers are preventable, tobacco being the largest most preventable cause of cancer in the world. - - Tobacco, particularly smoking, causes ⅓ - ½ of all cancer cases.
20
Q
Tobacco
A
smoke can kill epithelial cells that line the airway and the lungs
21
Q
Injury with relation to tobacco caused cancer
A
- when these cells die, it is up to stem cells to repair the damage.
- Stem cells exist at resting state, but they can grow when injuries require it.
- stem cells begin rapid asymmetrical cell division to repair the damage
22
Q
Repair with relation to tobacco caused cancer
A
epithelial layer restores and stem cells stop dividing
23
Q
resting state with relation to tobacco caused cancer
A
successful completion of repair.
- Exit cell cycle.
24
Q
Persistent activation with relation to tobacco caused cancer
A
because they are already growing, and moving, stem cells can be vulnerable to mutations
- repeated exposure to chemical mutagens from smoke causes them to reactivate.
25
damage from UV
Damage from UV radiation is cumulative; the risk for developing cancer increases over time with continued direct exposure to the sun.
26
are all cancers preventable?
No
- Although some cancers can be decreased by lifestyle changes and limited exposure to risk factors, most cancers tend to be a product of bad luck.
- Cells in the body can experience insults to its DNA, and when it escapes the protective mechanisms, cancer develops.
27
risk of lung cancer
6.8%
28
risk of liver cancer
0.6%
29
risk of brain cancer
0.6%
30
risk of thyroid cancer
1.3%
31
Stem cell renewal and cancer risk
Tissues with higher rates of stem cell divisions are at higher lifetime risk for developing cancer
32
Transformation of cancer cell
normal cell undergoes change in its genetic code, leading to a tumour cell, which can divide more rapidly than its unaffected neighbours
33
Tumour Heterogeneity
since each cancer cell can accumulate a different set of advantageous mutations, well-established cancers can be quite heterogeneous- representing tens or hundreds of genetically different cancer cells within the same tumour.
- Variants and subclones can offer different physiological characteristics
34
challenges with understanding cancer: Various Tissue Types
tissue types respond differently to treatments. Drugs used to treat breast cancer are not effective in treating brain cancer
35
challenges with understanding cancer: continuous mutation
- tumours can be heterogeneous as they contain different subclones. - - - Each subclone differs in its ability to metastasize as well as its response to cancer drugs.
- Poses a challenge to cancer treatment as not all cells that make up a tumour will respond to a drug.
36
Frequently Mutated Genes in Cancer
- Despite variabilities between cancers, there are regions of the genome that are commonly mutated.
- graph on slide shows that the cancers all have a common mutation in the TP53 gene
- Common mutations like this show that processes and the proteins associated with them are necessary in the evolution and inherent resilience of cancer
37
Cancer-Associated Genes
can be broadly categorized into two types: Oncogenes or tumour suppressor genes
38
Oncogenes
- once mutated, produce proteins with new or altered functions which provide growth advantages to cancer cells, unmutated forms and normal proteins they code for are called proto-oncogenes.
- Typically involved in growth factor receptor pathways that mediate embryonic growth, homeostasis and injury repair
- mutation in just one allele is sufficient for an oncogene to elicit pro-cancer effects.
- Cancer causing mutations turn growth stimulating proteins on that makes them impossible to turn off
- Gain of function mutations- produce cancerous effects as soon as theyre produced
39
Tumour Suppressor Genes
- contribute to cancer progression as mutations disable their normal functions usually associate with preventing uncontrolled growth and inducing cell death
- Other than acting as cell checkpoints, these genes play important roles in developmental processes that require apoptosis.
- both tumor suppressor alleles must be mutated to contribute to cancer progression
- Function to restrain cancer growth, loss of function mutation can cause cancer, if BOTH alleles have this mutation
- One allele on the chromosome can keep cancer at bay, even if the other one is non functional
40
can you be born with cancer?
no it emerges throughout lifetime
41
TP53
suppressor gene
- an extensively studied tumor suppressor gene,
- TP53 is mutated in some capacity in almost all cancers. - The protein product of TP53, is known as p53 which regulates cell division.
42
ERBB-1
oncogene
- codes for the protein epidermal growth factor receptor (EGFR)
43
p53
- The p53 protein, coded by this gene plays roles in determining cell survival and death.
- prominent role is responding to genomic damage by activating repair and or cell death programs
- prevents cells with cancer causing mutations from surviving. (Acts like brakes on a car)
- p53 deficient cells can tolerate or even thrive with oncogenic mutations which provide them with selective advantage over cells with p53 intact.
- a component of the G1/S checkpoint.
- If DNA damage is undetected before replication, the mutations will carry forward to future generations of that cell.
44
Activation of p53
- DNA damage leads to the activation and accumulation of normal p53.
- Binding of p53 to specific DNA sequences results in cell cycle arrest in G1and induction of DNA repair by transcriptional upregulation of repair genes
45
p53: DNA repair
- Proteins activated by p53 attempt to repair mutations in gene sequences.
- Successful repair of DNA allows cells to proceed with the cell cycle.
- If DNA repair fails, p53 triggers either apoptosis or senescence.
46
Inactive p53
- in cells with loss of or mutated TP53, DNA damage does not lead to p53 accumulation or binding of p53 to the specific DNA sequences.
- As a result, there is no cell cycle arrest and/or DNA repair.
- Cells with DNA damage can proliferate and eventually give rise to malignant tumours
47
stats about ERBB-1 gene
ERBB-1 gene was affected in over 25% of glioblastoma cases and almost 15% of lung adenocarcinomas.
48
How many genes are in the human growth factor effected family and what are they all considered?
20
- All are considered proto-oncogenes as they each have the potential to become oncogenes via mutations
49
EGFR
- detects extracellular signals or ligands, and forms dimers in order to transmit that signal into the cell, EGFR starts up a lot of processes associated with cell growth and survival. - - Signal is tightly regulated in normal cells to avoid unwanted proliferation.
50
Gene Expression Through EGFR
Receptor tyrosine kinase that detects extracellular ligands and induces gene expression.
51
Ligand binding (EGFR)
upon ligand binding components of EGFR undergo a structural change, activating the receptor
52
Phosphorylation (EGFR)
- structural change and activation of the receptor leads to a phosphorylation of EGFR in the cytoplasm. - - - - -
- Secondary messengers are also phosphorylated by the active EGFR. These activated messengers then transmit the signal to the nucleus.
53
Gene expression (EGFR)
EGFR signal thats been transmitted to the nucleus then increases transcription of genes involved in cell proliferation and survival, This signal also drives mechanisms outside the cell like cell migration across tissues and angiogenesis
54
Termination (EGFR)
Ligand is released or the receptor is broken down.
- can get broken down in lysosomes
55
Hyperactivation of EGFR
- some mutations can cause the EGFR activity to be hyperactivated.
- With the same amount of ligand binding, there are more secondary messengers that are activated than normal.
- This ultimately increases the signal being sent to the nucleus and ramps up pro-cancer processes (angiogenesis, cell proliferation, inhibition of apoptosis, migration adhesion and invasion)
56
Constitutive Activation of EGFR
- is able to signal without stimulus from a ligand.
- Given that there is no stimulus that initiates this signal, it can't be terminated and is active at all times, this results in pro-cancerous processes always being on
57
Chemotherapy and EGFR
does not target EGFR directly, but kills any rapidly dividing cells in the body
58
Antibodies and EGFR
EGFR ligand bonding domain is extracellular making it susceptible target for antibody-based therapies
59
Kinase inhibitors
- Both EGFR and its secondary messengers have kinase activity.
- Small molecule inhibitors can cross the plasma membrane and disrupt signalling cascades.
