Angela's Biologic Therapy

Question 1

What monoclonal antibodies inhibit EGFR?

Answer 1

Cetuximab, Panitumumab

Question 2

What is EGF?

Answer 2

Transmembrane tyrosine kinase protein growth factor

Upstream of KRAS, NRAS, BRAF, MEK

Question 3

What mABs inhibit EGFR?

Answer 3

Cetuximab, Panitumumab

Question 4

What agent targets HER2/ERBB?

Answer 4

Trastuzumab (Herceptin)

Question 5

Which test should be used to confirm number of DNA gene copies of ERBB2/HER2 prior to initiating treatment?

Answer 5

FISH

Question 6

What does herceptin target?

Answer 6

HER2 receptor

Question 7

What is the mechanism of action of bevacizumab

Answer 7

Monoclonal antibody against VEGF-A, preventing it from binding VEGFR-1 and 2 on endothelial cells

Question 8

What is the MOA Farletuzumab?

Answer 8

Folate receptor alpha monoclonal antibody

Far - folate alpha receptor

Question 9

What small molecular inhibitor is an oral RAF and VEGFR inhibitor?

Answer 9

Sorafenib

Mnemonic
Ora - oral
Raf

Question 10

What small molecular inhibitor is an PDGFR and VEGFR inhibitor?

Answer 10

Sunitinib

Think: It’s always SUNNY in PDGFR VEGFR (Philadelphia). It’s a stretch, I know.
AW edit: Pazopanib (VEGFR, both PDGFR-a/b), Lenvatinib (VEGFR, PDGFR-a), Sorafinib (VEGFR, PDGFR-b)

Question 11

What small molecular inhibitor is an EGFR inhibitor?

Answer 11

Gefitinib (Iressa)

Mnemonic
Ge.f - EGFr
Erlotinib

Question 12

What small molecular inhibitor is an EGFR and ERBB2 inhibitor?

Answer 12

Lapatanib
(and neratinib- JS)

Question 13

What small molecule drug targets c-kit, bcr-abl, PDGFR (as well as stem cell factor)?

Answer 13

Imatinib

Question 14

What is imatinib approved for?

Answer 14

GIST and CML

Question 15

What is the most common side effect of bev?

Answer 15

hypertension

Question 16

Where is the gene locus encoding progesterone receptors PRA and PRB?

Answer 16

11q22-23
AW: 11q22 (not sure about -23)

Question 17

What are the 6 regions of steroid receptors (A-F)?

Answer 17

A/B – most variable
C (DNA-binding zinc fingers) and E (Ligand-binding dimerization – most conserved
D – Hinge region
F – Ligand specificity

Question 18

Hormone receptors have (——-) affinity and (——-) capacity

Answer 18

HIGH affinity
LOW capacity

This means they are easily saturable

Question 19

Mechanism of estrogen receptor signalling

Answer 19

Estrogen enters the plasma membrane and binds intracellular ERα and ERβ to exert direct effects by binding to DNA sequences (nuclear). It can also activate intracellular signaling cascades.
ERα - ovary
ERβ - testis, kidney, thymus, small intestines

FYI: Sex steroid (estrogen, androgen, progesterone) receptors are intranuclear, whereas glucocorticoid receptors (GR) are located totally or in part in the cytoplasm of cells in the absence of hormone

Question 20

Mechanism of progesterone receptor signalling

Answer 20

Progesterone binds the PGR to promote the transcription of target genes. It is a nuclear receptor. PGR binds hormone and enters into the nucleus to bind DNA to initiate downstream functions within the cell.

FYI Sex steroid (estrogen, androgen, progesterone) receptors are intranuclear, whereas glucocorticoid receptors (GR) are located totally or in part in the cytoplasm of cells in the absence of hormone

Question 21

ER/PR signalling

Answer 21

Hormone-bound receptor dimerizes and binds to a specific DNA site, the hormone-responsive Element (HRE). This alters the activity of the promoter gene and results in transcription of target genes.

ER and PR are NUCLEAR RECEPTORS - active in the nucleus
ER is initially membrane bound, but moves to intranuclear once it binds its ligand
PR is always intranuclear