Cancer Mutations and Meds Flashcards Preview

CMOD Block 2 > Cancer Mutations and Meds > Flashcards

Flashcards in Cancer Mutations and Meds Deck (55):
1

HER2 is commonly _____ in ______ cancer.

over-expressed in breast cancer
(marker of a poor prognosis)

2

HER2 is targeted with what 2 therapies?

Trastuzumab
TDM-1 (mAb with chemo)

3

c-Kit is commonly _____ in ______.

constitutively active in GIST

4

Mutated c-Kit is targeted by what drug?

Imatinib

5

EGFR is commonly ____ or ____ in what 2 types of cancer?

overexpressed or mutated to be constitutively active in adenocarcinomas of the lung AND head/neck cancers

6

EGFR in LUNG CANCER is targeted using what drug?

Erlotinib

7

EGFR in Head and Neck cancer is targeted using what drug?

Cetuximab (external blockage!!)

8

KRas is commonly ____ in what 3 cancers?

mutated to be constitutively active in colon, pancreatic, and small cell lung carcinoma

9

NF-1 is an example of what?

a GAP (GTPase activating protein) that helps inactivate Ras(GTP) to stop the tyrosine kinase signaling cascade
(tumor supressor gene)

10

NF-1 is _____ in _____.

GERMLINE mutated (disabled) in neurofibromatosis type 1
OR
TUMORAL mutated (disabled) in neurofibromas

11

B-Raf V600 is commonly ____ in ____.

mutated to be overproduced in melanomas

12

B-Raf V600 mutation is treated using what drug?

Vemurafenib

13

EML4-ALK is commonly ___ (with what effect) in ____.

Rearranged to make Ras constitutively active in NSCLC (adenocarcinoma)

14

Cancer with EML4-ALK is treated using what drug?

Crizotinib

15

BRC-ABL is a reciprocal translocation of what 2 chromosomes?

9 (ABL) and 22 (BCR)

16

A BCR-ABL translocation (Philadelphia chromosome) is seen in what type of cancer?

CML

17

At what point in the signaling pathway does BRC-ABL work?

It stimulates activation of everything downstream of Ras

18

How do you treat someone with a BCR-ABL translocation?

Imatinib mesylate (Gleevec)

19

TMPRSS-ETS is a ____ seen in ____. What effect does it have?

Fusion gene seen in prostate cancers that leads to cell survival (mTOR pathway)

20

MEN1 is ____ in ____. What effect does it have?

upregulated in multiple endocrine neoplasia syndrome that stimulates mTOR for cell survival

21

Src is ___ in ____. What effect does it have?

overexpressed due to rearrangement in colon cancer (leading to constant signaling through tyrosine kinase pathway)

22

What is the role of MYC?

activates CDS, represses CDKIs, upregulates genes for the Warburg effect

23

What are the two possibilities for MYC dysregulation in cancer? What cancers are these seen in?

8,14 translocation in Burkitt's Lymphoma

Amplification of NMYC (double minutes or homologously staining region) in Neuroblastomas (children, NOT in brain)

24

HMGA2 is ____ in _____.

Rearranged (so that the 3'-UTR is replaced with another gene that removes miRNA that was repressing it) in Pleomorphic Parotid Adenoma

25

What are the "big 4" mutations?

Cyclin D
CDK4
CDKN2A (p16)
Rb

26

In Breast, Esophagus, liver, and other cancers, Cyclin D is ______.

amplified or overproduced due to a rearrangement

27

What types of cancers do you find CDK4 amplified?

melanomas
Sarcomas
glioblastomas

28

To lead to cancer, would CDKN2A be suppressed or activated?

deleted/inactivated (because this is a CDKI)

29

In what cancers do you see tumoral CDKN2A mutations?

pancreatic and glioblastomas (also esophageal and NSCLC)

30

In what cancers do you see germline CDKN2A mutations?

25% of melanomas

31

Hypophosphorylated Rb does what?

Binds strongly to E2F, preventing it from going to the nucleus and stimulating transcription of Cyclin E (to push cell over G1/S checkpoint)

32

Hyperphosphorylated Rb does what?

Releases E2F which allows cell to progress thorugh the G1/S checkpoint (because Cyclin E is being transcribed)

33

A germline mutation in Rb leads to what?

Retinoblastoma (can be bilateral) and osteosarcoma ONLY if second hit occurs

34

p53 is usually in very low concentrations. What two methods break down p53?

MDM2 and HPV E6 oncoprotein

35

What does p53 do if it senses cell damage?

Tells p21 to prevent cyclin D/CDK phosphorylation of Rb (so cell cycle will halt in G1
OR
stimulates apoptosis by activating Bax

36

BCL2 is commonly ___ in ____.

14.18 rearrangement (so overexpressed) in follicular lymphomas

37

APC is commonly ____ in _____.

Mutated in 100% colon cancer with familial polyposis and 70% of sporatic colon cancers

38

What is the effect of an APC mutation?

cannot break-down Beta-cetenin, so it goes to the nucleus and stimulates transcription of TWIST and SLUG (which represses E-cadherin) and Cyclin D1 and MYC (growth promoters)

39

NF2 produces a protein called what?

merlin

40

What is the role of Merlin?

facilitates E-cadherin mediated contact inhibition

41

What happens if you have homologous loss of NF2?

neurofibromatosis type II

42

What is the effect of a mutated VHL?

cannot break down HIF-1alpha, so it is free to go to nucleus and upregulate transcription of VEGF which leads to angiogenesis

43

VHL mutation is called ____ and leads to _____.

Von Hippel-Lindau disease that leads to renal cell carcinoma

44

How do you treat VHL disease?

sunitinib (prevents VEGF signaling through RTK)

45

VEGF is in VERY high levels in what type of cancer?

glioblastomas

46

What drug is given to block VEGF receptors?

Bevacizumab

47

What is present in some breast cancer that is a good target for therapy?

estrogen receptor

48

What drug can be used to target estrogen receptor positive breast cancer?

tamoxifen (also for adjuvant therapy)

49

What drug is given if tamoxifen therapy fails to treat ER positive breast cancer?

everolimus (mTOR inhibitor)

50

What is present in prostate cancer that serves as a drug target?

androgen receptor

51

What are the multiple places you can target androgen-driven prostate cancer?

pituitary stimulus blockers prevent androgen synthesis
blockage AT the androgen receptor
alock DHT/AR from entering the nucleus

52

What drug prevents DHT-androgen receptor from going into the nucleus?

enzalutamide

53

Sonic Hedgehog is mutated in what type of cancer?

basal cell carcinoma

54

What happens with a sonic hedgehog mutation?

PRCH is forced to release SMO so it can go to the nucleus and drive proliferation

55

How do you treat a sonic hedgehog mutation?

vismodegib