Molecular Testing in the Diagnosis of Cancer Flashcards
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
Molecular Diagnostic Methods
Real time pcr
dna sequencing
array
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
Qualitative Testing
Diagnostic mutation analysis
ex) tracking of B and T cell rearrangements
ex2) HPV testing
High risk forms of HPV
16, 17
low risk forms of Hpv
6, 11-genital warts
Quantitative Molecular oncology testing
minimal residual disease/tumor burden
ex) Chronic myelogenous leukemia– philadelphia chromosome and bcr-abl in 95% of cases
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
pharmacogenetics
use genetic informaton to predict drug response (metabolism) in patent with same dx taking a certain drug
PGXm
studying metabolism- how fast person metabolizes drug
PGXt
targeted treatment
irinotecan
topoisomerase inhibitor used for colon cancer
metabolism of irinotecan
CPT-11 (orally)–>SN 38 active form–> UGT1A1 (enzyme)–>SN 38 glucouronide (inactive)–>excreted
mutation in UGT1A1 promoter
increase in TA repeats above 7–> BM toxicity & increased diarrhea
should use diff drug/lower doses
syndromes where this mutation is seen
Criger-Najjar Type 1
Gilbert’s Syndrome (hyperbilirubinemia)
immediate effects of chemo
extravasation
emesis
hypersensitivity
tumur lysis
early effects chemo
myelosuppression
mucositis
alopecia
cystitis
delayed effects chemo
cardiotoxicity lung fibrosis P. neuropathy hepatotoxicity nephrotoxicity
late effects chemo
second cancer
encephalopathy
sterility
teratogenicity
her2 gne
codes for an estrogen receptor linked to signal transduction pathways that promote cell replication
–35% breast cancers–>multiple copies her2–>more replication
herceptin
a mAb specific for her2 to secreen breast cancers for increased her2 so that tamoxifen (a her2 antagaonist) can be used
most common carcinoma in non-smokers
non-small celllung carcinoma
what is special about non-small lung carcinoma?
conventional cytotoxic chemo has little effect
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
