Properties of Cancer Cells Flashcards
1
Q
How many people worldwide does cancer affect?
A
1 in 3
2
Q
What was the cancer incidence in the UK in 2007?
A
297,991
3
Q
What was the cancer mortality in the UK in 2007?
A
156,723
4
Q
How many people that get cancer die from it?
A
Only about half
5
Q
What were the top 4 most commonly diagnosed cancers in the UK in 2007?
A
Breast
Lung
Colorectal
Prostate
6
Q
What were the top 4 most common causes of death from cancer in the UK in 2007?
A
Lung
Colorectal
Breast
Prostate
7
Q
Define cancer
A
A group of diseases characterised by an unregulated increase in cell number, and invasion and metastasis
8
Q
When is a tumour classed as benign?
A
If the neoplastic cells are clustered in a single mass
9
Q
When is a tumour classed as malignant?
A
Once the tumour cells have undergone metastasis
10
Q
Cancer is a single disease, true or false?
A
False, it is a group of diseases
11
Q
How many types of cancer have been classified?
A
> 100 types
12
Q
In what characteristics do cancers differ?
A
Tissue of origin Causal factor(s) Molecular mechanisms
13
Q
How are tumour types classified?
A
According to the tissue of origin?
14
Q
What type of tissue are carcinomas derived from?
A
Epithelial cells
15
Q
What type of tissue are sarcomas derived from?
A
Mesenchymal cell types
16
Q
What type of tissue are leukaemias derived from?
A
Haemopoietic cells
17
Q
What type of tissue are neuroectodermal cancers derived from?
A
Nervous system tissue
18
Q
What type of tissue are melanomas derived from?
A
Neural crest origin tissues
19
Q
What type of tissue do the majority of cancers arise from?
A
Epithelial tissues, i.e. carcinomas
20
Q
Give an example of a carcinoma
A
Small-cell lung carcinoma
21
Q
Give an example of a sarcoma
A
Liposarcoma
22
Q
Give an example of a leukaemia
A
Multiple myeloma
23
Q
Who described the hallmarks of cancer in the year 2000?
A
Weinberg and Hanahan
24
Q
What are the 4 hallmarks of cancer that contribute to an increase in cell number?
A
Sustaining proliferative signalling
Evading growth suppressors
Enabling replicative immortality
Resisting cell death
25
What do cancer cells need to do in order to form tumours?
They need to become immortal
26
What are the emerging hallmarks of cancer?
Deregulating cellular energetics
| Avoiding immune destruction
27
What are the enabling characteristics of cancer?
Genome instability and mutation
| Tumour-promoting inflammation
28
What do the hallmarks of cancer drive?
Tumourigenesis
29
What do the enabling characteristics of cancer promote?
Tumour progression
30
Where can classical and enabling hallmarks be exploited in?
Designing cancer therapies
31
Give examples of epithelial cells
Skin
| Gut
32
Give examples of mesoderm cells
Bone
| Muscle
33
Give an example of glandular tissue
Breast
34
Give an example of haemopoietic cells
Blood
35
What is the name given to the type of cancer that arises in the glandular tissue?
Adenocarcinoma
36
What percentage of cancers are of epithelial origin?
85%
37
Where are epithelial cells found?
Lining external and internal surfaces of organs
38
What are epithelial cells the targets of?
Environmental mutagens
39
Cancer is a genetic disease, true or false?
True
40
What does cancer result from?
Alterations in DNA, i.e. mutations
41
What does the accumulation of mutations over time underlie?
Carcinogenesis
42
What are genetic changes that occur within a cell responsible for inducing?
The hallmarks of cancer
43
What causes most cancers?
Environmental factors, i.e. infectious agents and lifestyle
44
What happens to the cancer rates in migrants which is strong evidence of the role of environment in cancer incidence?
They become similar to those in the local population
45
The incidence of human cancer does not increase with age, true or false?
False, the incidence of human cancer increases with age
46
What percentage of deaths from cancer worldwide are associated with infectious agents such as viruses and bacteria?
~20%
47
What percentage of deaths from cancer worldwide are caused by environmental factors arising from our lifestyle?
~70%
48
What do DNA repair enzymes do?
Fix mutated DNA
49
What enzymes can cancer cells have defects in?
DNA repair enzymes
50
What do tumour initiators do?
Cause damage to DNA
51
What do tumour promoters do?
Do not damage DNA but promote cell proliferation
52
What do inherited defects in repair genes lead to?
Cancer susceptibility
53
Give an example of a cancer susceptibility syndrome
Li-Fraumeni syndrome
54
What does the cell cycle checkpoint between G1 and S phase check?
Have growth factor signals been received?
55
What does the cell cycle checkpoint between S and G2 phase check?
Is DNA duplication complete?
56
What does the cell cycle checkpoint between G2 and M phase check?
Is the cell ready to enter into mitosis?
57
What does the cell cycle checkpoint between M and G1 phase check?
Is mitosis complete?
58
Are cancer cells able to escape cell cycle checkpoints?
Yes
59
How are cancer cells able to sustain proliferative signalling?
By escaping cell cycle checkpoints
60
What are the 6 main hallmarks of cancer?
```
Sustaining proliferative signalling
Evading growth suppressors
Enabling replicative immortality
Resisting cell death
Inducing angiogenesis
Activating invasion and metastasis
```
61
What are the phases of the cell cycle?
G1, S, G2, M
62
At what stage of the cell cycle can arrest occur?
Between M and G1 phase
63
Why does cell cycle arrest occur in normal cells?
To allow for cell differentiation
64
How are cancer cells able to evade growth suppressors and thus evade growth inhibition?
By escaping the cell cycle arrest checkpoint
65
What is the Hayflick limit?
Normal human cells explanted and grown in culture have a limit in their capacity to proliferate
66
How are cancer cells able to enable replicative immortality?
By overcoming the Hayflick limit
67
How many cells need to be present in a tumour to make it first visible on an x-ray?
E8 cells
68
How many cells need to be present in a tumour to make it first palpable?
E9 cells
69
How many cells need to be present in a tumour to allow it to cause the death of the patient?
E12 cells
70
How are cancer cells able to resist cell death?
By evading apoptosis
71
What would DNA damage/death signals normally lead to in normal cells?
Apoptosis
72
What is the initial cell called in haemopoiesis?
Pluripotent haematopoietic stem cell (HSC)
73
What types of cells can be produced during haemopoiesis?
Granulocytes, monocytes, eosinophils, erythrocytes, megakaryocytes, T and B cells of the immune system
74
What is leukaemia?
A collection of diseases that result from an increase in cell number
75
From which cells does chronic myelogenous leukaemia (CML) arise from?
Pluripotent stem cells
76
From which cells do acute lymphocytic leukaemia (ALL) and lymphoma arise from?
Lymphoid progenitor cells
77
From which cells does acute myeloid leukaemia (AML) arise from?
Myeloid progenitor cells
78
Why is the gastrointestinal tract a common site of tumours?
Due to a large amount of cell replenishment occurring
79
What is angiogenesis?
The development of a blood supply
80
Why do normal cells depend on blood vessels?
To supply oxygen and nutrients to the cells
81
Why do cancer cells induce angiogenesis?
In order to survive and expand
82
How do normal cells derive the bulk of their ATP?
Through oxidative phosphorylation
83
How do cancer cells derive the bulk of their ATP?
Through glycolysis (the Warburg effect)
84
Do cancer cells show an enhanced or decreased mutation rate? What does this promote?
Enhanced, promoting the formation of malignant cancer
85
Are cancer cells genetically stable or unstable? What does this promote?
Unstable, promoting the formation of malignant cancer
86
Give an example of a therapeutic that targets the evasion of growth suppressors in cancer cells
Cyclin-dependent kinase inhibitors
87
Give an example of a therapeutic that targets the avoidance of immune destruction in cancer cells
Immune activating anti-CTLA4 mAB
88
Give an example of a therapeutic that targets the enablement of replicative immortality in cancer cells
Telomerase inhibitors
89
Give an example of a therapeutic that targets the sustainment of proliferative signalling in cancer cells
EGFR inhibtors
90
Give an example of a therapeutic that targets the deregulation of cellular energetics in cancer cells
Aerobic glycolysis inhibitors
91
Give an example of a therapeutic that targets the resistance of cell death in cancer cells
Proapoptotic BH3 mimetics
92
Give an example of a therapeutic that targets the genome instability and mutation in cancer cells
PARP inhibitors
93
Give an example of a therapeutic that targets the induction of angiogenesis in cancer cells
Inhibitors of VEGF signalling
94
Give an example of a therapeutic that targets the activation of invasion and metastasis in cancer cells
Inhibitors of HGF/c-Met
95
Give an example of a therapeutic that targets the tumour-promoting inflammation in cancer cells
Selective anti-inflammatory drugs
96
What does cancer result from?
Genetic changes to the DNA
97
Some individuals inherit a strong susceptibility to cancer. Give examples of diseases that are cause by rare germline mutations and increase cancer susceptibility in affected individuals
Retinoblastoma
Skin cancers
Breast cancer
98
Is there any variation between countries in the incidence of some common cancers?
Yes
99
Give an example of a human cancer causing virus and the cancer it causes
Hepatitis C virus (HCV)
| Causes some hepatocellular carcinoma and some lymphomas
100
Whereabouts in the body does the papillomavirus often infect?
The cervix
101
Give an example of a human cancer causing bacteria and the cancer it causes
Helicobacter pylori
| 30% of gastric carcinomas and 100% of gastric mucosa-associated lymphoid tissue (MALT) lymphoma
102
What are the top 4 lifestyle causes of cancer?
Tobacco
Diet
Reproductive hormones
Alcohol
103
Tumour promoters can cause cancers anywhere in the body?
No, they often have specific sites of action
| E.g. chewing tobacco can cause cancers in the oral cavity
104
Are DNA damaging agents (initiators) diverse or not?
They are diverse
105
Give some examples of chemical carcinogens
Polycyclic aromatic hydrocarbons
Aromatic amines
Azo dyes
106
What are the carcinogenic ionising radiations (in descending order of energy release)?
Atomic particles
X-rays
Ultraviolet light
107
Give an example of a chemical carcinogen that can act directly on DNA
Alkylating agents
108
Give an example of a chemical carcinogen that becomes active after it is metabolised
PAH
109
What enzymes convert PAHs to ultimate carcinogens?
Cytochrome P-450 enzymes
110
What does exposure to UV cause?
DNA damage
111
What do UV photons frequently induce which leads to mutation?
Pyrimidine dimers
112
How does ionising radiation damage DNA?
Directly or by the production of reactive oxygen species
113
What do reactive oxygen species react with?
DNA or other biomolecules to create DNA damage
114
What was the result of the carcinogenic effect of the Chernobyl nuclear accident in 1986?
Local inhabitants were exposed to E-1 Gy causing a 2% increase in lifetime cancer risk
115
What test can be used to test for mutagenicity?
The Ames test
116
In a single day, how many single strand breaks occur to DNA in one human cell?
20,000
117
In a single day, how many alkylating lesions occur to DNA in one human cell?
5000
118
In a single day, how many double strand breaks occur to DNA in one human cell?
10-20
119
In a single day, how many depurination events occur to DNA in one human cell?
10,000
120
In a single day, how many oxidative lesions occur to DNA in one human cell?
2000
121
In a single day, how many deaminations occur to DNA in one human cell?
600
122
Cells are able to deploy a variety of defenses to protect DNA from attack by mutagenes, give examples of these
Physical shielding
Detoxification enzymes
DNA repair enzymes
123
What do repair enzymes do?
Fix mutated DNA
124
Give examples of DNA repair enzymes
Mismatch repair (MMR) enzymes
Methylguanine DNA methyltransferase (MGMT) enzymes
Base excision repair (BER) enzymes
Nucleotide excision repair (NER) enzymes
125
What do repair enzymes do?
MMR enzymes repair nucleotides of normal structure in wrong positions whereas others repair nucleotides of abnormal structure
126
What do MGMT enzymes do?
Remove methyl or ethyl adducts from the O6 position of guanine caused by alkylating agents, e.g. ENU
