Millikan B IHO Week 3

Question 1

3 reasons that we have not been able to cure more patients with chemotherapy?

Answer 1

1. altered threshold for apoptosis 2. drug avoidance mechanisms 3. toxicity to the host

Question 2

What was the first drug to target Bcl-2 to restore pro-apoptotic signals

Answer 2

Venetoclax

Question 3

What mimics the action of BH3 domain (an inhibitor of Bcl-2) to promote apoptosis

Answer 3

Venetoclax

Question 4

Curative

Answer 4

only a fraction of patients will be cured

Question 5

Control

Answer 5

treatment that has less than 5% chance of cure

Question 6

what is the phrase for using agents of different mechanistic classes

Answer 6

non-cross resistant

Question 7

Name a large natural product that induces DNA strand breaks; MOA unkown

Answer 7

Bleomycin

Question 8

What causes potentially fatal pulmonary fibrosis; higher is smokers and prohibitive in presence of pulmonary hemorrhage or pulmonary embolism?

Answer 8

Bleomycin

Question 9

Combination used for germ cell tumors in Stage 2 ds

Answer 9

BEP (Bleomycin, Etoposide, Cisplatin)

Question 10

Combination that is standard tx for intermediate risk non-Hodgkin lymphoma, in favorable risk patients, 80% curative

Answer 10

R-CHOP (Rituximab, Cytoxan, Doxorubicin, Vincrisitne, Prednisone)

Question 11

Standard tx for Hodgkins’s, favorable risk cure is 90%

Answer 11

ABVD (Doxorubicin, Bleomycin, Vinblastine, Prednisone)

Question 12

Standard induction for AML, 20-30% cure

Answer 12

3+7 (Daunrubicin, Ara-C)

Question 13

Standard adjuvant treatment for breast cancer

Answer 13

AC–>T (Doxorubicin, Cyclophosphamide, Taxane)

Question 14

What combines well with DNA damaging agents (including radiotherapy?)

Answer 14

Gemcitabine

Question 15

What is much safer from a cardiac perspective, but more prone to cause hand/foot syndrome and is the first liposomal cancer drug

Answer 15

Liposomal Doxorubicin

Question 16

Drug very active agains CD30 expressing lymphomas, built from antibody and a highly toxic anti-tubule drug that is too toxic to use non-targeted

Answer 16

Brentuximab Vedotin

Question 17

Used in breast cancers that overexpress Her2, built from an antibody and a highly toxic anti-tubule drug that is way too toxic to be used in a non-targeted way

Answer 17

Trastuzumab-Maytansine (T-DM1) aka ado-trastuzumab

Question 18

A polymer with camptothecin

Answer 18

CRLX101

Question 19

signal transduction inhibitor, ligand reduction, small, breast cancer

Answer 19

Anastrozole

Question 20

signal transduction inhibitor, receptor antagonist, MAB, Her2 over expressing Breast and upper GI cancers

Answer 20

Trastuzumab

Question 21

signal transduction inhibitor, receptor antagonist, MAB, EGFR driven cancers of aerodigestive tract

Answer 21

Panitumumab

Question 22

signal transduction inhibitor, receptor antagonist, small, breast cancer

Answer 22

Tamoxifen

Question 23

signal transduction inhibitor, receptor antagonist, small, Prostate

Answer 23

Enzalutamide

Question 24

signal transduction inhibitor, receptor antagonist, peptide, prostate and breast

Answer 24

Leuprolide

Question 25

signal transduction inhibitor, TKI, small, B cell malignancies, especially CLL

Answer 25

Ibrutinib

Question 26

signal transduction inhibitor, TKI, small, CML, GIST, Ph+ALL

Answer 26

Imatinib

Question 27

signal transduction inhibitor, TKI, small molecule, lung cancers with ALK or ROS1 activation, c-met overexpressing thyroid cancer

Answer 27

Crizontinib

Question 28

signal transduction inhibitor, TKI, small molecule, renal cell carcinma, C-kit driven cancers

Answer 28

Pazopanib

Question 29

3 ways to lower hormone concentration

Answer 29

1. decrease synthesis (turn down synthesis stimulus, direct drug based inhibition) 2. increase catabolism 3. neutralizing antibody to 'soak up' all the hormone

Question 30

Decrease Testosterone

Answer 30

1. remove testicles and/or adrenals 2. pituitary gland 3. remove pituitary gland 4. use LHRH antagonist 5. LHRH super-agonist or super-agonist or antagonist 6. inhibitor of steroid biosynthesis 7. use a neutralizing antibody

Question 31

what binds very strongly to the LHRH receptor and INCREASES in LH and testosterone for a couple of days and then paradoxical fall; nearly no side effects

Answer 31

LHRH (aka GnRH) superagonists

Question 32

What will you see iatrogenic osteoporosis consequences of worsening insulin resistance and intervention-requiring affective disorders in up to 30%?

Answer 32

LHRH super agonists (Leuporlide and Goserelin)

Question 33

What has no 'flare' but is a pure antagonist that results in castrate testosterone levels within 24 hours

Answer 33

Dagarelix

Question 34

what is a steroid analog expected to bind to several enzymes in metabolic pathway; must be given with physiologic replacement of adrenocorticoids?

Answer 34

Abiraterone (lyase inhibitor)

Question 35

How to block testosterone?

Answer 35

block conversion of T to DHT (5-alpha-reductase) and block androgen receptor (AR)

Question 36

What is a great target with minimal tweaking of all the other steroids would be expected (slightly higher androgen)?

Answer 36

The final step of estrogen synthesis (Aromatase)

Question 37

What is an aromatase inhibitor that causes arthralgia and myaligia sufficient for patients to stop taking the drug in about 20% of patients?

Answer 37

Anastrozole

Question 38

Name an aromatase inhibitor that is also a suicide substrate and can cause arthralgia and myalgia

Answer 38

Exemstande

Question 39

Name a selective estrogen recetpor modulator (SERM); it is not a full antagonist

Answer 39

Tamoxifen

Question 40

Name a pure estrogen receptor antagonist that generally outperforms tamoxifen

Answer 40

Fulvestrant

Question 41

What is a metabolite of Tamoxifen that is 100x more potent; how do you get to it?

Answer 41

Endoxifen; via CYP3A4/5 to CYP2D6

Question 42

TK

Answer 42

Tyrosine Kinase

Question 43

Ligan binding domain versus tyrosine kinase domain

Answer 43

extracellular versus intracellular

Question 44

Various adapter proteins connect the RTK phosphorylation event to various 'second messengers.' Name one specifically

Answer 44

SH2 domains-recognize phospho-tyrosine

Question 45

What causes degradation of HIFalpha

Answer 45

prolyl hydroxylase, vitamin C, a-ketoglutarate, oxygen all combine to cause ubiquitin attachment with help of E3 ligase activity

Question 46

What happens if HIF alpha is constitutively active (low oxygen state)?

Answer 46

induction of hypoxia-inducible genes (VEGF, PDGF)

Question 47

TKI

Answer 47

tyrosine kinase inhibitor

Question 48

AE of VEGFR inhibitors

Answer 48

htn, hypothyroidism, loss of hair pigmentation, rare: GI perforation, pericardial effusion, myelosuppression, hepatic toxicity

Question 49

Member of the EGFR family, marker of clinically aggressive ds, intracellular kinase activity w/NO LIGAND BINDING DOMAIN, effects different based on heterodimer

Answer 49

Her2 aka Erb-B2

Question 50

humanized antibody to the extracellular domain of the Her2 protein, combination with chemotherapy metastatic breast cancer improvement, used in adjuvant

Answer 50

Trastuzumab

Question 51

Blocks both the EGFR and Her-2 with more AE

Answer 51

Lapatinib (TKI)

Question 52

5% of patients with adenocarcinoma of the lung will have what issue

Answer 52

EGFR activating mutation or activated ALK signaling

Question 53

Who is most likely to respond to EGFR directed therapy

Answer 53

patients with del exon 19 or L858R

Question 54

in RTK drivers in lung cancer which patients are most likely to have resistance

Answer 54

T790M mutation

Question 55

Which meds to use in TKIs in lung cancer? Which do you use with a T790M mutation?

Answer 55

Gefitnib or erlotinib; with resistance use Osimertinib