Brainscape's Knowledge GenomeTM

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


See full index

OSD_GI > Colorectal Cancer > Flashcards

Colorectal Cancer Flashcards

1
Q

Of the following, which are tumor suppressor genes, which are oncogenes, & which are DNA repair enzymes?

p53, APC, hMSH2, SMAD, ras, MYH, DCC, c-myc, hMLH1

A

Oncogenes: ras, c-myc

Tumor Suppressor: APC, p53, DCC, SMAD

DNA Repair Genes: hMSH2, hMLH1, MYH

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

In what test is the K-Ras mutation detectable?

A

Mutations detectable in stool

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

Which gene, when inactivated, promotes the formation of other pro-oncotic mutations?

A

p53 (chromosome 17)
b/c it normally arrests the cell at the G1/S checkpoint, permitting the cell to locate & fix other mutations.
w/out this “repair time”, other mutations accumulate
(thus correlates w/ poor prognosis)

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

Name the gene defects in each step of the microsatellite instability pathway:

Normal
(a)  
-- DNA hypomethylation --
Early adenoma
(b)
Advanced Adenoma
(c)
Invasive cancer (& may lead to metastases)
A

a) APC
b) K-ras
c) p53

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

What is the rate-limiting step for initiation of most CRC?

A

APC mutation

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

~70% of FAP has what mutation?

A

APC mutation – 90% of these are a truncated APC protein

other 30% sporadic

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

What is the central mutational cause of Hereditary Non-Polyposis Colorectal Carcinoma?

A

Faulty DNA Mismatch Repair

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

Compare HNPCC & Sporadic Colorectal Carcinoma:

Age at diagnosis?

A

HNPCC: 45

Sporadic: 67

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

Compare HNPCC & Sporadic Colorectal Carcinoma:

Frequency of multiple colon cancers?

A

HNPCC: 35%

Sporadic: 4-11%

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

Compare HNPCC & Sporadic Colorectal Carcinoma:

Proximal locatin?

A

HNPCC: 72%

Sporadic: 35%

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

Compare HNPCC & Sporadic Colorectal Carcinoma:

Excess malignant tumors at other sites? (yes or no)

A

HNPCC: Yes

Sporadic: No

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

Compare HNPCC & Sporadic Colorectal Carcinoma:

Prognosis?

A

HNPCC: Favorable

Sporadic: Variable

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

What is the Amsterdam Criteria used for?

A

Used to determine if people have are likely to have Lynch Syndrome (HNPCC)

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

What are the Amsterdam Criteria?

A

3 : 2 : 1

3 relatives w/ an HNPCC-ass’d cancer (CRC, endometrial, SB, ureter/renal pelvis)

2 generations spanned

1 at age <50

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

Are DNA Replication Errors a common theme of:

  • HNPCC?
  • Sporadic Colorectal Carcinoma?
A

HNPCC: Yes (79%) (mostly Microsatellite Instability genes)

Sporadic: No (17%)

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

What is a polyp?

A

Visible protruding mass covered w/ mucosa

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

What does it mean to refer to polyps as sessile or pedunculated?

A

Sessile = Flat

Pedunculated = Stalked

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

What clinical diagnosis is made that calls for a prophylactic colectomy in young adulthood?

A

Familial Adenomatous Polyposis (FAP)

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

What type of gene is BAT26?

A

Microsatellite Instability gene

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

Some symptoms of Colorectal Carcinoma?

A
  • Melena/Hematochezia
  • Iron Deficiency Anemia
  • Change in bowel habits (stool caliber & frequency)
  • Abdominal pain
  • NO symptoms!
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is Carcinoembryonic Antigen?

A

Cell Surface Adhesion Glycoprotein that can be elevated in a variety of cancers such as Colorectal, Breast, Lung, & Gastric
- Expressed in 80-85% of Colon Cancers

  • It’s also elevated in non-cancer states such as Colitis, Pancreatitis, Cirrhosis, & Smoking
    (therefore not useful for screening)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Is Carcinoembryonic Antigen useful for screening?

A

No, but it may be useful for prognosis & follow-up

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

What are some poor prognostic factors for Colon Cancer?

A
  • Obstruction or Perforation
  • Elevated Carcinoembryonic Antigen pre-op
  • Fewer nodes removed at surgery (minimum = 12)
24
Q

What are some “good” prognostic factors for Colon Cancer?

A
  • Microsatellite Instability
  • – ass’d w/ HNPCC
  • Lower stage
25
Q

3 major differences between Colon vs. Rectal cancers?

A 
Colon = Melena
Rectal = Hematochezia

Rectal = much HIGHER risk of relapse after surgery

Rectal = usually require local RADIATION b/c of higher risk of relapse post-surgery

26
Q

General Tx for Stages I-IV: Colon Cancer

A 
Stage I (small tumor, negative nodes)
- Surgical resection
Stage II (bigger tumor, negative nodes)
- Surgical resection
~~ Post-op Chemo if Stage IIb or perforation / obstruction / lymphovascular invasion

Stage III (positive nodes)

  • Surgical resection
  • Post-op Chemo

Stage IV (distant metastases)

  • Chemotherapy
  • Surgery may play role if…
  • – Bowel obstruction
  • – Bleeding
  • – Isolated liver metastases

**note: rectal cancer is same, except add Radiation @ stages 2-3 & definite chemo @ 2

27
Q

General Tx for Stages I-IV: Rectal Cancer

A 
Stage I (small tumor, neg nodes)
- Surgical resection

Stage II (bigger tumor, neg nodes)

  • Pre- or post-operative Radiation & Chemo
  • Surgical Resection
  • Postoperative Chemo

Stage III (positive nodes)

  • Pre- or post-operative Radiation & Chemo
  • Surgical Resection
  • Post-operative Chemo

Stage IV (distant metastases)

  • Chemotherapy
  • Most will need surgery or radiation for palliation of primary tumor
28
Q

Fluorouracil- absorption?

A

Poor oral absorption
(rapidly taken up into cells & phosphorylated)

Capecitabine is oral prodrug

29
Q

Fluorouracil- MOA?

A

Interferes w/ DNA

  • Inhibits Thymidylate Synthase
  • Incorporated into DNA

Interferes w/ RNA

30
Q

Fluorouracil- Toxicities?

A
  • Myelosuppression
  • Mucositis
  • Diarrhea
  • Photosensitivity
  • Hand-foot Syndrome

Uncommon:

  • Cardiac Syndrome
  • Biliary Fibrosis
31
Q

A congenital deficiency of Dihydropyrimidine Dehydrogenase in 0.5% of population, puts you at risk for what?

A

Increased Fluorouracil toxicity

32
Q

Leucovorin- use/effects?

A

Augments the cytotoxicity/effectiveness of Fluorouracil

Leucovorin is Reduced Folate

33
Q

What is Capecitabine?

A

Oral prodrug of Fluorouracil

b/c Fluorouracil is poorly absorbed

34
Q

What are the 2 current standard drugs used for adjuvant therapy of Colorectal Cancer?

A

Fluorouracil

    • Capecitabine (oral prodrug)
    • Leucovorin (augments effect)

Oxaliplatin

35
Q

Fluorouracil is a _____ _____ (type of drug)

A

Halogenated Pyrimidine

36
Q

Oxaliplatin- MOA?

A

Mainly forms N7-d(GpG) intrastrand adduct

  • blocks DNA replication
  • blocks Transcription

*adduct = combo of 2 or more compounds

37
Q

How is resistance to Oxaliplatin mediated?

A

Nucleotide Excision Repair Genes

38
Q

Oxaliplatin- method of delivery?

A

IV only (undergoes non-enzymatic conversion)

39
Q

Oxaliplatin- Toxicities?

A
  • Myelosuppression
  • Peripheral neuropathy
  • Diarrhea
  • Mucositis
40
Q

Metastatic (stage IV) Colorectal Cancer:

  • Median Survival?
  • Cure?
A

~2 yrs.

Currently no cure

41
Q

Colorectal Cancer: Hematogenous & Local metastatic tendencies?

A

Hematogenous:

  • Liver
  • Lungs
  • Bone, Brain

Local

  • Intra-abdominal
  • Intra-pelvic
42
Q

Drugs for Metastatic (stage IV) Colorectal Cancer?

A
  • Fluorouracil
  • Oxaliplatin
  • Irinotecan
  • Bevacizumab
  • Cetuximab/Panitumomab
43
Q

Irinotecan- MOA?

A

Topoisomerase I inhibitor

44
Q

Irinotecan- Resistance mechanisms?

A
  • Impaired transport/Enhance efflux
  • Topoisomerase mutations
  • Enhanced metabolism
45
Q

Irinotecan- method of delivery?

A

IV only

46
Q

Irinotecan- Toxicities?

A
  • Myelosuppression
  • Diarrhea
  • Mucositis
47
Q

Bevacizumab- MOA?

A

Humanized anti-VEGF antibody

48
Q

Bevacizumab- method of delivery?

A

Given by vein w/ chemotherapy

49
Q

Bevacizumab- Toxicities?

A
  • Hypertension
  • Thrombosis
  • Bleeding
  • Infusion rxns
  • Inc toxicity of chemotherapy
50
Q

Cetuximab/Panitumomab- MOA?

A
  • Antibodies directed at extracellular domain of EGFR

- Block binding of EGF to receptor

51
Q

Cetuximab/Panitumomab- Toxicities?

A
  • Rash
  • Diarrhea
  • Mucositis
52
Q

Cetuximab/Panitumomab- Mechs of Resistance?

A

Activating mutations in K-ras & BRAF render cells resistant to antibodies

(these convey poor natural history)

53
Q

@ what stage does post-operative Chemotherapy become standard use in Colorectal Cancer?

A

Stage III

sometimes used in Stage II

54
Q

@ what stage does Chemotherapy become standard use in Rectal Cancer?

A

Stages II & III

55
Q

@ what stage does Radiation become standard use in Rectal Cancer?

A

Stages II & III

56
Q

T or F? Stage IV Colorectal Cancer is incurable, but Tx prolongs life.

A

True

OSD_GI (13 decks)

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