Molecular Testing in the Diagnosis of Cancer Flashcards Preview

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Flashcards in Molecular Testing in the Diagnosis of Cancer Deck (28):
1

5 ideal drug target

- drives tumor growth
-turns on key mechanisms of cancer progression
- reversible by inhibition
- dispensable in normal cells
-target is measurable in tumor tissue used for diagnosis

2

Molecular Diagnostic Methods

Real time pcr
dna sequencing
array

3

challenge of molecular oncology testing

-normal genome vs. cell genome
-primary vs metastasis
-heterogeneity-- tissue vs. tumor
-% tumor cell content
-recurrence- accurate testing of minimal residual disease
-monitoring

4

Qualitative Testing

Diagnostic mutation analysis
ex) tracking of B and T cell rearrangements
ex2) HPV testing

5

High risk forms of HPV

16, 17

6

low risk forms of Hpv

6, 11-genital warts

7

Quantitative Molecular oncology testing

minimal residual disease/tumor burden
ex) Chronic myelogenous leukemia-- philadelphia chromosome and bcr-abl in 95% of cases

8

Rx goals in CML (3)

1- hematological- normal pb value and spleen size
2- cytogenic response- reduction of ph+ cells in blood/bone marrow
3- molecular response- reduction or elimination of bcr-abl mrna in marrow or pb

9

pharmacogenetics

use genetic informaton to predict drug response (metabolism) in patent with same dx taking a certain drug

10

PGXm

studying metabolism- how fast person metabolizes drug

11

PGXt

targeted treatment

12

irinotecan

topoisomerase inhibitor used for colon cancer

13

metabolism of irinotecan

CPT-11 (orally)-->SN 38 active form--> UGT1A1 (enzyme)-->SN 38 glucouronide (inactive)-->excreted

14

mutation in UGT1A1 promoter

increase in TA repeats above 7--> BM toxicity & increased diarrhea

should use diff drug/lower doses

15

syndromes where this mutation is seen

Criger-Najjar Type 1
Gilbert's Syndrome (hyperbilirubinemia)

16

immediate effects of chemo

extravasation
emesis
hypersensitivity
tumur lysis

17

early effects chemo

myelosuppression
mucositis
alopecia
cystitis

18

delayed effects chemo

cardiotoxicity
lung fibrosis
P. neuropathy
hepatotoxicity
nephrotoxicity

19

late effects chemo

second cancer
encephalopathy
sterility
teratogenicity

20

her2 gne

codes for an estrogen receptor linked to signal transduction pathways that promote cell replication
--35% breast cancers-->multiple copies her2-->more replication

21

herceptin

a mAb specific for her2 to secreen breast cancers for increased her2 so that tamoxifen (a her2 antagaonist) can be used

22

most common carcinoma in non-smokers

non-small celllung carcinoma

23

what is special about non-small lung carcinoma?

conventional cytotoxic chemo has little effect

24

EGFR

Receptor tyrosine kinase-- two mutations make it constiuently active (fram del 19 and pt mutation 21)

if people have this mutation, can give anti-EGFR mAbs, but need to test to see if they have it first

25

colorectal carcinomas with mutated KRAS

resistant to Rx with panitumamb

26

KRAS mutations are associated with

smoking

27

more about KRAS mutations

occurs most often in codons 12 and 13

missence mutations (change of amino acid)

7 common mutations

28

successfully screening for more than 1 biomarker

high density microarray analysis
next generation sequencing