Brainscape's Knowledge GenomeTM

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


See full index

PHAM02 > GI cancer SD > Flashcards

GI cancer SD Flashcards

1
Q

inherited mutation at APC gene that increases risk of CRC

A

familial adenomatous polyposis (FAP)

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

What is FAP?

A
  • familial adenomatous polyposis
  • inherited mutation in the APC gene
  • formation of many polyps on the colon mucosa
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

risk of CRC with FAP

A

100% lifetime risk

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

How is FAP diagnosed?

A

colonscopy and genetic testing

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

What type of mutations are in the APC gene that cause FAP?

A

mostly point mutations

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

What type of gene is APC?

A

tumour suppressor gene

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

variant forms of FAP

A

attenuated FAP - specific APC mutants, fewer polyps

MUTYH-associated FAP - mutations in MUTYH gene implicated in base excision repair, autsosomal recessive inherited

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

RF for CRC

A
  • diet - red meat, processed meats, dec risk with fibre, chicken, fish
  • lack of physical activity
  • obesity
  • alcohol
  • smoking
  • genetic predisposition
  • protective effetive of aspirin

-> 54% cases preventable through lifestyle

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

gene mutations that can cause CRC

A

KRAS

BRAF

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

Where is IBD related CRC most common?

A

ascending colon

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

Where is sporadic CRC most common?

A

descending colon, sigmoid colon and rectum

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

How long does it take for adenoma to develop into advanced carcinoma?

A

17 years

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

How long does it take for progression from early carcinoma to metastasis?

A

1.8 years

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

staging system for CRC

A

Duke’s Stage A-D

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

most common site for metastases in CRC

A

liver (50% of CRC patients)

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

2nd most common site for metastases in CRC

A

lung

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

Vogelstein model

A
  • model of how CRC arises
  • stepwise accumulation of mutations/epigentic changes and how these form tumours in CRC
  • genes - APC, KRAS, p53
18
Q

screening for CRC

A
  • faecal occult blood test
  • measure of blood in stool
  • testing cards sent to home, posted to lab for analysis
19
Q

guaic faecal occult blood stool test

A

card coated with guaic resin, faeces applied by patient

hydrogen peroxide developer solution applied

detects haemoglobin activity

20
Q

limitations to the guaic faecal test

A
  • red meat, cauliflower, uncooked veg, haemorrhoids all give false positives
  • high vitamin C gives false negative
21
Q

gold standard screening for CRC

A

colonoscopy

22
Q

strict diet days before colonoscopy

A

low fibre
only clear liquids

laxatives to prep bowel

23
Q

difference between flexible sigmoidoscopy and colonscopy

A
  • sigmoidoscopy only covers the descending colon
  • colonscopy provides full coverage of colon
24
Q

advantages of sigmoidoscopy over colonoscopy

A
  • like colonoscopy, can remove polyps/ademonas and take biopsies
  • only covers descending colon but this is where most sporadic CRC tumours originate, coverage for 70-80% CRC cases
  • no sedation required
  • reduces cost
  • shorter duration (10mins vs 30mins)
25
Q

When would colonoscopy be used instead of sigmoidoscopy?

A

preferred for colitis-associated CRC

26
Q

main Tx for CRC

A

surgery to remove the tumour and chemotherapy to reduce the risk of metastases

chemotherapy can be given before surgery to shrink tumour size or after surgery to reduce the chance of recurrence

27
Q

When does adjuvant chemotherapy usually begin after surgery?

A

6 weeks after

28
Q

Is radiotherapy used?

A

no, not common

USED IF:

  • not clear if tumour completely removed (attached to lining of abdomen)
  • patient not healthy enough for surgery
  • more common in rectal cancer as adjuvant therapy to prevent recurrence (stage 2-3)
29
Q

3 signalling and targeted therapies for CRC

A
  1. EGFR inhibitors
  2. VEGFR inhibitors
  3. immunotherapy
30
Q

How to EGFR inhibitors work?

A

target EGFR (epidermal growth factor R) that promotes tumour growth

31
Q

How to VEGFR inhibitors work?

A

target VEGF (vascular endothelial growth factor) that promotes growth of neovasculature

32
Q

How does immunotherapy work?

A
  • target PD-L1 which is expressed on tumours to block immune response
  • PD-1 inhibition increases immune response to the tumour
  • given to patients not responding to chemotherapy
33
Q

How can EGFR signalling promote CRC?

A
  • EGFR activation stimulates multiple downstream pathways
  • these drive cellular proliferation and promote cell survival (anti-apoptosis)
  • components frequently mutated in CRC - activates the pathways irrespective of EGFR activity
  • KRAS
  • BRAF
  • PI3K
  • PTEN
34
Q

How can EGFR signalling promote CRC?

A
  • EGFR activation stimulates multiple downstream pathways
  • these drive cellular proliferation and promote cell survival (anti-apoptosis)
  • components frequently mutated in CRC - activates the pathways irrespective of EGFR activity
  • KRAS
  • BRAF
  • PI3K
  • PTEN
35
Q

What should be tested before Tx for metastatic CRC suitable for systemic Tx? Why?

A

RAS and BRAF V600E mutations in all patients suitable for systemic anti-cancer Tx

it effects Tx choice, mutated receptors, resistance

WT patients can receive cetuximab/Panitumumab -> EGFR MAbs

mutate RAS means this therapy is ineffective

36
Q

What does VEGF do?

A

tumour secretes VEGF

VEGF increases blood vessel expression and movement to tumour

tumour has increased blood supply

37
Q

MAb for VEGF

A

Bevacizumab (Avastin)

38
Q

Where do mutations in KRAS mostly cause CRC?

A

sigmoid
rectum

39
Q

Where do mutations in BRAF mostly cause CRC?

A

ascending
tranverse colon

40
Q

genetic alterations that can be in metastatic CRC that prevent cells from repairing damaged DNA

A

dMMR - mismatch repair deficiency

MSI-H - high microsatelite instability

41
Q

What do dMMR and MSI-H cause?

A
  • prevent cells from repairing DNA damage
  • leads to high rates of DNA mutations
  • some mutations can lead to production of abnormal antigens that can be targeted by immune cells
42
Q

MAb that targets PD-L1 (programmed death ligand 1)

A

Pembrolizumab

PHAM02 (32 decks)

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