Year 1 What is Cancer? Flashcards
1
Q
Define cancer?
A
- An abnormal growth of cells
- multiply in an uncontrolled way
- in some cases metastasize
2
Q
Define tumour or neoplasm?
A
- abnormal mass of tissue growing in an uncontrolled or uncoordinated matter
- can be benign or malignant
3
Q
What are neoplastic cells?
A
- lost control of normal processes such as growth
- irreversible process, cannot go back to being normal cells
4
Q
Define a mutation
A
Abnormal change in a gene
5
Q
Define oncology
A
Study of tumours or neoplasia
6
Q
Define benign tumours
A
Grow locally and do not invade nearby tissue
7
Q
Define malignant tumours
A
May invade nearby tissues and metastasise
8
Q
Define metastasis
A
Spread of cancer cells from primary tumour to surrounding tissues and distant organs
- can develop a secondary tumour
9
Q
Define carcinogenesis
A
multi-step process transforming normal cell to a cancer cell
10
Q
Define transformation
A
Conversion of one cell phenotype to another
11
Q
Define carcinogen
A
An agent which changes a cell population and can cause cancer
12
Q
Define carcinoma
A
Cancer which arises from the epithelium of the skin or internal organs
13
Q
Define differentiation
A
Process by which cell develops/matures allowing it to perform a specific function
14
Q
What is cancer?
A
- unregulated growth of malignant tumours
- can invade surrounding tissues and metastasise
- caused by a number of mutations (multi-hit process)
- can be solid or haematological malignancies
15
Q
What is the significance of cell signals?
A
- cancer cells do not require external signals to tell them to grow as mutations over-ride this signalling
16
Q
What cells are needed for tumour development?
A
- immune inflammatory cells
- endothelial cells for vasculature for oxygen
- pericytes
- cancer associated fibroblast
- stem cell
- cancer cell
- invasive cancer cell
17
Q
What are the 6 hallmarks of cancer?
A
- self sufficiency in growth signals
- insensitivity to anti-growth signals
- evade apoptosis
- limitless reproductive potential
- sustained angiogenesis
- tissue invasion and metastasis
18
Q
How do cancer cells have self sufficiency in growth signals?
A
- normal cells require mitogenic growth signals to move into active proliferative state
- oncogenes in cancer mimic normal growth and tumour cells generate own growth signals (autocrine signalling)
19
Q
How are cancer cells insensitive to anti-growth signals?
A
- normal cells have anti-proliferative signals maintaining cellular quiescence
- growth inhibitory signals received by transmembrane cell surface receptors coupled to intracellular signalling
- antigrowth signals block proliferation by forcing out cells from cell cycle in G0 or induce cells to enter post mitotic state for terminal differentiation
20
Q
How do cancer cells evade apoptosis?
A
- determined by rate of proliferation and cell attrition
21
Q
How do cancer cells have a limitless replicative potential?
A
- maintain the telomeres so do not shorten preventing apoptosis
22
Q
What are the enabling characteristics of cancer cells?
A
- modify metabolism to support growth
- evade destruction by immune system (exploited by immunotherapy)
- genomic instability promote more genetic alterations
- inflammation by immune cells are tumour promoting
23
Q
What is a proto-oncogene?
A
- responsible for cell growth, division, motility
- undergo mutations in cancer cells creating uncontrolled growth
- once mutated = becomes an oncogene
- gain of function
24
Q
What are tumour suppressor genes?
A
- allow cell to stop at checkpoint in cell cycle and allow DNA repair
- if mutation cell mutation is not stopped and replication is continued
- loss of function as DNA repair cannot occur
25
What are the 5 categories of proto-oncogenes?
- growth factors
- growth factor receptors
- signal transduction proteins
- transcription factors
- pro or anti apoptotic proteins
26
What is an example of GF overexpression?
- VEGF = BPH
- PDGF = glioblastoma
- TGFa elevated levels = oesophageal cancer
- HER2/ErB2 = breast cancer
27
What happens if the HER2/ErB2 GF is overexpressed?
- uncontrolled growth
- mutated cells survive
- tumour cells invade
- tumour cells migrate
(receptor activated when GF absent, unregulated autocrine loops)
28
What is an example of a signal transduction proteins?
- K-ras
- normally binds to GTP causing phosphate to phosphorylate K-ras and activate it, protein gets dephosphorylated and deactivated in a normal cell (under control of phosphorylation)
- phosphorylated k-ras activates ERK pathway
- when K-ras mutated, GTP very slowly very slowly hydrolysed to GDP so K-ras phosphorylated for longer and activating MAP kinase pathway for longer (major growth pathway)
29
What is an example of a TF?
- c-MYC regulates normal functions (cell cycle, DNA replication, cell adhesion, differentiation, growth, metabolism)
- promotes transcription of cyclin genes which promote cell cycle progression
- elevated expression in cancer cells
- c-MYC translocations = Burkitt lymphoma
- c-MYC overexpression = breast cancer, colon, lung
30
What is the difference between c-MYC translocations and overexpression?
- overexpression alone cannot induce tumorigenesis
| - need additional translocations and evade tumour suppressing checkpoints to induce tumorigenesis
31
What are the significance of apoptotic and anti-apoptotic proteins?
- cancer cells undergo up regulation of anti-apoptotic proteins
- survive even when challenged by DNA damaging compounds
- balance between Bax (anti-apoptotic) and Bcl-2 (pro-apoptotic) required for normal apoptosis as form a dimer
- mutation within Bax = apoptosis
- increased Bcl-2 = cells immortalised
- In B cell lymphomas translocation of Bcl-2 occurs using stronger promoter of immunoglobulin gene to evade apoptosis
32
How do tumour suppressor genes work?
- act to block development of cancer
- mutations enable loss of function of these genes and therefore lose restriction of cell growth enabling tumour survival
33
How do tumour suppressor genes restrict cell proliferation?
- control cell cycle and division
| - induce apoptosis when other mechanisms have failed
34
What do mutations of tumour suppressor genes do?
- act recessively releasing cells from growth control
- greatly increase probability of mutations
- may prevent apoptosis or allow or allow cell division of mutated cells
35
What are gatekeeper genes?
- type of tumour suppressor genes
- stop cell cycle progression when DNA damage is detected
- p53 TF mutations are most common genetic alteration in cancer
- pRB transcription inhibitor
(both examples of gatekeeper genes)
36
What is the function of p53?
- TF
- activated by DNA damage, hypoxia or cell injury
- activates p21 to inhibit cyclin complex preventing cell leaving G1 and entering S phase
- cell cycle arrest/DNA repair/entry to apoptotic pathway
- mutant p53 = cells progress through cycle with DNA damage and so mutations accumulate becoming cancerous
37
What is the function of pRB?
- prevents cell cycle progression past G1 phase by inhibiting S phase genes
- mutant pRB = retinoblastoma
38
What are caretaker genes?
- maintain genomic stability
- repair DNA damage during cell cycle arrest
- BRCA (DNA repair protein) (breast and ovarian cancer)
- MMR (mismatch repair genes)
39
What are BRCA1 and BRCA2?
- breast cancer
- repair damaged dsDNA crosslinks at G2/M checkpoint
- loss = strand breaks and aneuploidy after cell division
40
What is BRCA1?
- interacts with cyclins and CDKs triggering CDK inhibitor, p21 and p53 = controls cell cycle
- involved in DNA repair
- if BRCA1 deficient = genomic instability
41
What is BRCA2?
- facilitates homologous recombination
| - if deficient = cannot recruit ssDNA binding proteins to repair double strand breaks from homologous recombination
42
What are the physiological factors of cancer cells?
- growth signals not required for survival, growth and differentiation
- unresponsive to growth inhibitory signals
- evasion of apoptosis
- defects in DNA repair
- cells become immortal
- ability to invade and metastasise
- angiogenesis sustained and increased
