Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

EMS MOD > mollecular hallmarks of cancer and carcinogenesis > Flashcards

mollecular hallmarks of cancer and carcinogenesis Flashcards

1
Q

what are the main characteristics of the biological hallmarks of cancer?

A

there is no one single feature - they have acquired capabilities of cancer but not all cancers have the same acquired functional capabilities - various mechanistic strategies to acquire these

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

how are biological hallmarks used?

A

6 main and they are later used for prognosis, prediction and treatment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what are the six main biological hallmarks of cancer?

A

sustained angiogenesis, evading apoptosis, tissue invasion and metastasis, self sufficient in growth signals, insensitive to anti growth signals and limitless replicative potential

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what are other biological hallmarks of cancer?

A

avoiding immune destruction, tumour promoting inflammation, deregulating cellular energetics, genome instability and mutations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what is meant by self sufficiency in positive growth factors?

A

a lot of signally pathways and targeted and changed in carcinogenesis. The most fundamental trait of cancer is the ability to sustain chronic proliferation. This occurs through signals by growth factors that bind to cell surface receptors and generally contain the intracellular tyrosine kinase domain. This then signals into the cell and the intracellular signalling pathways will regulate the progression through the cell cycle and growth

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

how are cancer cells monitored?

A

they are not monitored by the outside they progress independently.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

how do tumours commonly evade growth supressors?

A

Rb protein is a key regulator of the cell cycle and controls the progression if G1 to S phase. There is negative GF control of the Rb protein - GF will inhibit the cell cycle by activating the Rb protein. A mutation in the Rb gene will render it resistant to the negative growth factor and make it inactive, therefore there is no gatekeeper between G1 and S phase.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

how do tumours often evade immune destruction?

A

very often a tumour cell will have an infiltration of immune cells into the surrounding cells. There will be interaction between the tumour and immune cells.
The tumour cell will express receptor PD1 which will bind to T cell PDL1 - silences the T cell so cannot attack

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

how can the interaction between the T cell and tumour be stopped?

A

inhibitors can stop this through blocking binding. The antigen of the T cell and the T cell receptor of the tumour cell bind, anti PDL1 will bind to the PD1 receptor on the tumour cell and anti PD1 to the T cell and therefore it cannot bind with T cell a

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

how do cells normally stop replicating?

A

each cycle of replication the telomere of the daughter cell gets shorter so there is a finite replicative life

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

how can tumour cells enable replicative immortality?

A

the can maintain the length of the telomere and telomerase - infinite divisions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what is tumour inflammation?

A

there is dense inflammatory infiltrate of some tumours compared to others - the tumour associated inflammation can promote the progression of the tumour and cancer and therefore it benefits the tumour.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

how can tumours be divided?

A

into categories depending on inflammation - different prognosis and amount of immune therapy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what are some cytokines that are released in TAI?

A

IFN-y, IL-6 and TNF-a

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

how can a tumour metastasise?

A

cancer becomes dysplastic and changes from a low to high grade dysplasia - breaks through the basal lamina and the ability to metastasis grows - can go to the endothelium of blood vessels and then metastasise into different tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what influences metastasis?

A

the tumour type

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what is less worrying for a tumour?

A

when it has not metastasised - can locally destruct but not systemically
when there is a normal tumour that has a lining around it

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

how does metastasis result in a secondary tumour?

A

the cells will adhere to and penetrate a capillary wall and then through extravasation will form a secondary tumour once dividing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what process can be targeted in cancer therapy by antibodies?

A

inducing angiogenesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

how is angiogenesis induced?

A

small tumour will grow and will send different messangers to capillaries - these will start to grow and will supply the tumour will blood, oxygen and nutrients

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

how can angiogenesis aid the formation of secondary tumours?

A

the supply of nutrients and oxygen can help the spread

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

how does genomic instability help the tumour?

A

the instability allows it to progress quicker as it can react to changes more quickly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

what are the three outcomes of DNA damage?

A

single stranded - apoptosis or DNA repair

double stranded - DNA repair or senescence/arrest

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

what is the deregulation of metabolism in cancer cells?

A

where normal tissue has oxidative or anaerobic pathways that will produce different ATPs depending on the pathway, tumour cells are adapted to lack of O2 and therefore do anaerobic metabolism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

what are proto-oncogenes?

A

they are normal genes that promote cell proliferation, survival and angiogenesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

what are oncogenes?

A

they are mutated versions of proto that result in the increased expression/ overactivation of protos and therefore the increased and uncontrolled activity of expressed proteins - they are cancer causing agents

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

what does dominant gain-of-function mean?

A

oncogenes have this - it means that one mutant copy of the gene acts dominantly to the remaining normal parental gene
mutation in one of the two alleles is sufficient

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

where is the mutation to make oncogenes?

A

in somatic cells - it is not inherited

there is some tissue preference

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

what are TSGs?

A

they act to maintain checkpoints such as Rb and p53. They control genomic stability

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

how will a mutation be expressed in a TSG?

A

it is recessive so both copies of the gene/both alleles need to be affected - a mutation in one can easily happen when born

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

what does a mutation in TSG result in?

A

loss of function of protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

where are mutations of TSGs?

A

they can be inherited i.e. in a germ cell or in a somatic cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

which tissues are affected by TSG mutations?

A

there is strong tissue preference such as the effect of the Rb gene in the retina

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

what are proto-oncogenes for?

A

they encode for a protein that us directly involved in control of cell proliferation and can allow for checkpoints to be overcome - Ras and myc

35
Q

are proto-oncogenes dominant?

A

yes

36
Q

how can a proto-oncogene progress to cancer?

A

a proto-oncogene with a cancer promoting agent such as UV light or chemicals becomes an oncogene which can make a cancerous cell

37
Q

what are the four mechanisms of oncogene activation?

A

translocation, point mutation, amplification or insertion

38
Q

how does translocation of an oncogene work?

A

the oncogene is translocated from a site of low to active transcriptional activity - therefore there is aberrant expression of the oncogene which will produce a fusion gene - happens in Burkitt’s lymphoma

39
Q

how does point mutation activate an oncogene?

A

there is substitution of a single base within the amino acid sequence resulting in a hyperactive oncogene with a changed protein or no change at all

40
Q

how does amplification activate an oncogene?

A

insertion of multiple copies of the oncogene resulting in increased expression such as HERT2 and therefore more signalling and growth

41
Q

how can insertion activate an oncogene?

A

a promoter or enhancing gene is inserted by retroviruses near to oncogene and therefore there is increased expression such as with HPV

42
Q

what are examples of oncogenes?

A

myc, RAS, RAF, HER2 and EGFR

43
Q

what is Ras?

A

it is a family of proteins with 3 genes - KRAS, HRAS and NRAS

44
Q

what is the HERT2 blocker used for?

A

it is a new blocking drug that is effective for outcome in breast cancer

45
Q

what are tyrosine kinases for?

A

they are involved in signalling for cell division and stimulation

46
Q

what leads to tumour growth and proliferation?

A

overactivation if the activating component

47
Q

with regards to HER2 what will a normal cell comprise?

A

a few HER2 receptors on outside, HER2 gene in nucleus

48
Q

with amplification and overexpression what will comprise a HER2 cell?

A

lots of HER2 receptors and genes - overexpression and proliferation

49
Q

what is the role of TSGs?

A

they are inhibitory genes with 2 types:
the antioncogenes or gatekeepers are negative regulators of the cell cycle and proliferation and positive regulators of apoptosis
the caretakers are for maintaining genomic stability

50
Q

how many mutations are needed in TSGs for loss of function?

A

2

51
Q

what are the mechanisms of loss in TSGs?

A 
carcinogens will induce molecular abnormalities in TSGs that result in reduced or absent protein expression or function 
inactivating point mutation 
deletions 
translocations
epigenetic silencing
52
Q

what is epigenetic silencing?

A

it is the methylation of the CpG islands in the promoter regions in the TSGs that inactivate those genes and the ones further downstream

53
Q

what is important to consider in TSG mutations?

A

they can be heritable - implications for family

54
Q

what is meant by loss-of-function in TSGs?

A

a mutation will inactivate and it will not work properly - there is no dominant as two need to be mutated to render it inactive

55
Q

what genes are implicated in what cancers?

A

p53 - breast
RB - retinoblastoma
APC - polyps in colon - may turn cancerous
BRCA1/2 - ovarian and breast
hMLH1/2 - DNA mismatch repair genes - CRC

56
Q

how can genotoxic stress affect p53 normally?

A

genotoxic stress can cause activation or tetramerization of p53. Tetramerization will lead to transactivation of target genes or mRNA processing. Transactivation can cause apoptosis and both can cause cell cycle arrest. Activation results in protein interaction resulting in apoptosis

57
Q

which cancer genes are associated with cancer syndromes?

A

TSGs such as retinoblastoma in children

58
Q

what is p53 central to?

A

the cell cycle and is therefore implicated in a range of cancers

59
Q

how can TSG mutations result in a familial cancer?

A

inheritance of a mutant copy of a TSG or caretaker gene - carriers suffer from a 70-90% chance of developing cancer depending on syndrome

60
Q

why does a caretaker mutation result in cancer?

A

caretakers promote genetic stability, with a mutation they are unable to do this and therefore the individual is predisposed to developing cancer

61
Q

what does the risk of developing cancer depend on?

A

the penetrance - not certain

62
Q

what cancer syndromes result from the TSG mutations in genes RB1, p53 and APC?

A

RB1 - retinoblastoma - primary tumour is retinoblastoma
p53 - Li Fraumeni - primary tumour is sarcoma and breast
APC - familial adenomatous polyposis - primary tumour is CRC

63
Q

what cancer syndromes result from mutations in the caretaker genes BRCA1/2 and hMLH1/2?

A

BRCA - familial breast cancer with primary tumour as breast and ovarian
hMLH - hereditary non-polyposis colorectal cancer - CRC and endometrial primary tumours

64
Q

where is the mutation in Lynch Syndrome?

A

germline (HNPCC)

65
Q

what testing is done for familial cancers?

A

immunohistochemistry stains
can see genetics and pathways
darker - overexpressed and paler - under
genetic counselling if have mutations

66
Q

what is the carcinogenic process if adenoma/carcinoma ?

A

there is oncogene activation and tsg inactivation. TSG inactivation leads to removal of growth inhibition. Oncogene action then leads to neoplastic transformation - neoplasia (abnormal growth and excessive division) then malignant neoplasia and then metastasis and invasion.

67
Q

what is expressed for replication immortality?

A

telomerase

68
Q

what are the drivers for transformation of normal to neoplastic cell?

A

minimum of 3-6 genetic alterations in adenoma carcinoma

69
Q

what is the clinical process of tumours?

A

diagnosis, prognosis, therapy, monitoring

70
Q

what is diagnosis?

A

identification of type and subtype - cannot yet tell if malignant

71
Q

what is prognosis?

A

looking for certain mutations which confer worse survival

72
Q

what is therapy?

A

predictive makers for therapeutic response and development of targeted drugs or gene therapies for personalised medicine

73
Q

what is monitoring?

A

response to treatment and directing relapse

74
Q

for carcinogenesis of colon cancer describe the genes and stages involved?

A 
normal epithelium 
mutation in APC - early adenoma 
mutation in KRAS - intermediate adenoma 
mutation is SMAD4 - late adenoma 
mutation in p53 - adenocarcinoma
75
Q

what are serum markers used for?

A

diagnosis adjunct or monitoring

76
Q

what serum markers are used in diagnosis adjunct?

A

AFP, CA125, hCG and PSA

77
Q

what serum markers are used in monitoring?

A

CEA, thyroglobulin

78
Q

why are serum markers not used for screening?

A

non have sufficient sensitivity or specificity

79
Q

how does HER2 link to breast cancer?

A

it is overexpressed in 30% of breast cancers

80
Q

what do patients with HER2 overexpression receive as therapy?

A

Herceptin - without the overexpression of HER2 receptors there is no beneficial effect

81
Q

how would you identify HER2 overexpression?

A

through FISH - lots of red compared to green shows amplification

82
Q

what do around 50% of CRC have?

A

a tyrosine kinase mutation in the KRAS gene

83
Q

what blocks EGFR?

A

cetuximab and panitumumab - licenced for those patients who have WT tumours

84
Q

what do cetuximab and panitumumab do?

A

they block to EGFR receptor so KRAS does not signal to BRAF, MEK and ERK/MAPK therefore there is no angiogenesis, proliferation, migration or survival

EMS MOD (28 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions