Chemo Lecture

Front 1

What is an example of 2-hit paradigm in cancer?

Back 1

Rb

Front 2

Trastuzumab

Back 2

Treats HER2 amplification

Front 3

That is an example of haplioinsufficiency in cancer?

Back 3

p53, even if only one gene one the risk of cancer increases

Front 4

What is an example of quasi-sufficiency?

Back 4

PTEN

Front 5

What steps are in multi-hit colon cancer?

Back 5

APC mutation -> KRAS mutation -> SMAD 2/4 Loss -> TP53 mutation/loss

Front 6

What are the 3 drugs used to treat myelosuppressors?

Back 6

1) EPO (Erythropoietin, normally in kidney and liver)
2) G-CSF (Granulocyte colony-stimulating factor)
3) GM-CSF (Granulocyte-macrophage colony-stimulating factor)

Front 7

What pathway does EPO signal through?

Back 7

JAK's

Front 8

What does G-CSF do?

Back 8

Stimulate production of neutrophils, can PEGylate to increase half-life

Front 9

What does GM-CSF do?

Back 9

Stimulates production of monocytes and granulocytes

Front 10

What chemo drug targets S-phase?

Back 10

Antimetabolites
1) Methotrexate
2) Thiopurine
3) 5-FU (Fluorouracil)

Front 11

What chemo drug targets G1-S phase?

Back 11

Topoisomerase II inhibitors
1) Etoposide
2) Teniposide
(Epipodophyllotoxins)

Front 12

What chemo drug targets M-phase?

Back 12

1) Taxoids
2) Vinca alkaloids

Front 13

What do alkylating agents (chemo drug) do?

Back 13

- Irreversibly change DNA (including cross-linking)

Nitrogen mustard

Front 14

What does Methotrexate do?

Back 14

- (like folic acid) inhibits dihydrofolate reductase

(antimetabolite)

Front 15

What do antimetabolites do?

Back 15

Retards DNA synthesis and inhibits protein synthesis

Front 16

What does Thiopurine do?

Back 16

- Purine analogs
- Mutigentic effect by pairing with both C and T
- (6-MP, 6-TG, Azathioprine)
- (antimetabolite)

Front 17

What does 5-FU (Fluorouracil) do?

Back 17

- Pyrimidine analog
- Blocks thymidylate synthase
- (antimetabolite)

Front 18

What does Vinca Alkaloids do?

Back 18

- Bind to tubulin and prevent mitotic spindle formation
- M-phase disrupter

Front 19

What does Taxoids do?

Back 19

- Pacliaxel/Taxol
- Induce polymerization/stabilization of microtubules
- isolated from tree bark
- M-phase disrupter

Front 20

What the 4 main (streptomyces derived) antibiotics used to treat cancer?

Back 20

1) Actinomycin D
2) Adriamycin
3) Mitomycin
4) Bleomycin

Front 21

What are Topotecan/Iriontecan

Back 21

Camptothecins (tree) family - Inhibits Topoisomerase I
- Breaks single-stranded DNA
- Topotecan - ovary
- Irinotecan - colon and rectum

Front 22

What is Etoposide, Teniposide?

Back 22

- Inhibit Topoisomerase II
- Breaks double-stranded DNA
- Epipodophyllotoxin family
- Mayapple plant
- G1-S inhibitor

Front 23

Cisplatin

Back 23

- Crosslinks DNA
- Treats carcinoma of testes, ovary, etc..

Front 24

As2O3

Back 24

Acute promyelocytic leukemia

Front 25

Asparaginase

Back 25

- Depletes Asn levels
- Acute lymphocytic leukemia

Front 26

Flutamide

Back 26

Anti-androgens for prostate carcinoma

Front 27

Tamoxifen

Back 27

Anti-estrogen for postmenopausal breast cancer

Front 28

Letrozole

Back 28

- Aromatase inhibitors
- Prevent conversion of testosterone to estradiol
- For advanced breast cancer

Front 29

Fulvestrant

Back 29

- Selective estrogen receptor downregulators
- Destroys estrogen receptor
- Given to tamoxifen-resistant patients

Front 30

What are the Cell cycle non-specific groups?

Back 30

1) Alkylating agents
2) Platinum analogs
3) Antitumor Anthracyclines antibiotics
4) Topoisomerase I inhibitors

Front 31

Nitrogen Mustard

Back 31

- Alkylating agents
- irreversibly cross-links DNA

Front 32

Doxorubicin (Adriamycin)

Back 32

Intercalates in DNA

Front 33

Mitomycin

Back 33

After intracellular activation, reacts with DNA and inhibits its synthesis

Front 34

Bleomycin

Back 34

Chelates metal ions leading to production of superoxide and hydroxide free radicals which cause DNA cleavage, lipid (and other) peroxidation

Front 35

Tretinoin

Back 35

- Retinoic Acid receptor targeter
- Used to treat acute promyelocytic leukemia (and acne) - Acid form of Vitamin A

Front 36

Alitretinoin

Back 36

- Retinoic acid receptor targeter
- Targets RAR and RXR
- Used to treat AIDS-related Kaposi' sarcoma

Front 37

Bexarotene

Back 37

- targets RXR
- Treats cutaneous T-cell lymphoma

Front 38

Fighting Hallmarks of Cancer:

Back 38

1. Sustaining proliferative signaling - EGFR inhibitors
2. Evading growth suppressors - Cyclin-dependent kinase inhibitors
3. Avoiding immune destruction - Immune activating anti-CTLA4 mAB
4. Enabling replicative immortality - Telomerase inhibitors
5. Tumor promoting inflammation - Selective anti-inflammatory drugs
6. Activitating invasion and metastasis - Inhibitors of HGF/c-Met
7. Inducing angiogenesis - Inhibitors of VEGF signalling
8. Genome instabilit and mutation - PARP inhibitors
9. Resisting cell death - Proapoptotic BH3 mimetics
10. Deregulating cellular energetics - Aerobic glycolysis inhibitors

Front 39

Imatinib/Gleevic

Back 39

i. Pathway - Tyrosine kinase inhibitor
ii. Treat- Ph+ Chronic Myeloid Leukemia, BCR-ABL fusion (Philadelphia chromo), Ph+ Acute Lymphocytic Leukemia

Front 40

Trastuzumab (Herceptin)

Back 40

i. Pathway - Monoclonal anti-HER2 antibody
ii. Treat - HER2/Neu breast cancers

Front 41

Lapatinib

Back 41

i. Pathway - Kinase inhibitor
ii. Treat - HER2/Neu breast cancers

Front 42

Erlotinib (Tarceva)

Back 42

i. Pathway - Kinase inhibitor
ii. Treat - EGFR, advanced NSCLC

Front 43

Gefitnib (Iressa)

Back 43

i. Pathway - Kinase inhibitor
ii. Treat - EGFR, advanced NSCLC

Front 44

Cetuximab (Erbitux)

Back 44

i. Pathway - prevents EGF binding, only if no K-Ras mutation
ii. Treat - squamous cell carcinoma and colon cancer

Front 45

Bevacizumab (Avastin)

Back 45

i. Pathway - prevents VEGF from binding to receptor
ii. Treat - colorectal cancer, NSCLC
a) Can be also used for age-related macular degeneration (instead of Lucentis)

Front 46

Sunitinib (Sutent)

Back 46

i. Pathway - VEGFRs, PDGFRs and cKit inhibitor
ii. Treat - Renal cell carcinoma and imatinib-resistant GIST

Front 47

Sorafenib (Nexavar)

Back 47

i. Pathway - VEGFRs, PDGFRs and cKit, Raf-1, B-Raf inhibitor
ii. Treat - Renal cell carcinoma and hepatocellular carcinoma

Front 48

Vemurafenib (Zelboraf)

Back 48

i. Pathway - V600E B-Raf inhibitor
ii. Treat - late-stage melanoma

Front 49

Bortezomib (Velcade)

Back 49

i. Pathway - 26S proteasome active site inhibitor
ii. Treat - multiple myeloma

Front 50

Azacitidine (Vidaza)

Back 50

i. Pathway - Reactivation of tumor suppressor gene by incorporating into DNA and RNA
ii. Treat - myelodysplastic syndrome (pre-leukemia)

Front 51

5-Aza-2'-deoxycytidine (Decitabine)

Back 51

i. Pathway - Reactivation of tumor suppressor gene but does not incorporate into RNA
ii. Treat - myelodysplastic syndrome

Front 52

Vorinostat/SAHA (Zolinza)

Back 52

i. Pathway - Deacetylation of histone
ii. Treat - T-cell lymphoma

Front 53

Romidepsin (Istodax)

Back 53

i. Pathway - Deacetylation of histone, isolated from natural bacteria
ii. Treat - T-cell lymphoma

Front 54

IL-2

Back 54

i. Pathway - Antigen binding to T-cell receptor leadings to Interleukin-2, JAK-STAT
ii. Treat - renal cell carcinoma and malignant melanoma

Front 55

IFN-α 2a

Back 55

i. Pathway - Response normally produced by viruses, JAK-STAT
ii. Treat - renal cell carcinoma

Front 56

IFN-γ

Back 56

i. Pathway - Response normally produced by viruses, JAK-STAT
ii. Treat - renal cell carcinoma

Front 57

Levamisole

Back 57

i. Pathway - non-specific immunostimulatory properties
ii. Treat - colon cancer, melanoma, head/neck cancer [withdrawn from market due to side effects]
- Used as cutting agent in cocaine

Front 58

Provenge (sipuleucel-T)

Back 58

i. Pathway - autologous cellulur immunotherapy to vaccinate own leukocytes
ii. Treat - prostate cancer

Front 59

Ipilimumab

Back 59

i. Pathway - Blocks CTLA-4(which arrests cell) to promote proliferation of t-cell
ii. Treat - prostate and lung cancer

Front 60

Denileukin Diftitox (Ontak)

Back 60

i. Pathway - Bind Diphtheria toxin to IL-2
ii. Treat - T-cell lymphoma

Front 61

Adcetris (brentuximab vedotin)

Back 61

i. Pathway - antibody conjugated to poison
ii. Treat - Hodgkin's and large cell lymphoma