3.1 Targeted Therapy - Shah

idk fam

what is targeted therapy?

A cancer treatment that targets proteins/genes associated with growth and metastasis of cancer

targeted therapy acts on _________

specific molecular targets

targeted therapy is ____ and chemotherapy is ____

a. cytotoxic, cytotoxic

b. cytostatic, cytotoxic

c. cytotoxic, cytostatic

d. cytostatic, cytostatic

b

chemotherapy acts on…

all rapidly dividing cells

why is companion diagnosis essential for targeted therapy? (3)

1. can tell if a pt would benefit from a specific targeted therapy

2. can tell if a pt would be at a higher risk for ADE from specific targeted therapies

3. can monitor treatment and progression in pts on targeted therapy

name the two types of targeted therapy

small molecule inhibitors

monoclonal antibodies

how do small molecule inhibitors work?

they enter cells and inhibit intracellular targets

SMIs:

1. admin route

2. typical targets

1. oral

2. kinases

monoclonal antibodies targets are …

on the cell surface

Which targets intracellular pathways?

a. small molecule inhibitors

b. monoclonal antibodies

a

mabs admin route

IV

common ADE of all targeted therapies (3)

diarrhea, liver problems, and skin problems

other ADE of targeted therapies include… (6)

HTN

Fatigue

Rash

Mouth sores

Nail changes

Loss of hair color

Which oncogene is most commonly mutated?

RAS

What happens when Ras is mutated?

cancer growth due to constant activation

what type of receptor is EGFR?

tyrosine kinase receptors

when EGFR is activated, it leads to…

increased proliferation

increased metastasis

decreased apoptosis

cells expressing EGFR are resistant to…

cytotoxins

Which receptor is important in breast cancer?

HER2

of the HER dimers, which is the most potent and activates RAS MAPK and the STAT pathways?

HER1/HER2

Cetuximab

1. class

2. what is its target?

1. mab

2. EGFRs

Erbitux

1. mab or SMI?

2. what is its target?

1. mab

2. EGFR

name 2 mabs that target EGFR

Cetuximab

Erbitux

which drugs targets HER2

Trastuzumab

pertizumab

pertizumab

1. mab or SMI?

2. target?

1. mab

2. HER2

Trastuzumab

1. mab or SMI?

2. target?

1. mab

2. HER2

Trastuzumab MOA

downregulates HER2 signaling by masking protease cleavage site and blocking shedding of the receptor

ultimately leads to activation of the TK domain to

panitumumab

1. mab or SMI?

2. target

1. mab

2. EGFR

consequences of HER targeted therapies

drug resistance

name 4 tyrosine kinase inhibitors

Afatinib

Erlotinib

getitinib

osimertinib

Afatinib

1. mab or SMI?

2. target

3. fatal ADE

1. SMI

2. TK EGFR, HER 2, and HER4

3. intersitial lung disease, sepsis, and pneumonia

Erlotinib

1. mab or SMI?

2. target

3. most common ADE

1. SMI

2. TK EGFR

3. rash and diarrhea

Gefitinib

1. mab or SMI?

2. target

1. SMI

2. TK EGFR

Osimertinib

1. class

2. target

1. SMI

2. TK EGFR

Sunitinib

1. mab or SMI?

2. target

1. SMI

2. EGFR

Sorafenib

1. mab or SMI?

2. target

1. SMI

2. multikinase, serine, threonine, and tyrosine kinases

what does ALK code for

tyrosine kinases

MOA of ALK tyrosine kinase inhibitors

competitive inhibition of the ATP binding site on the ALK receptor

cizotinib

1. class

2. target

1. SMI

2. ALK receptor

ceritinib

1. mab or SMI?

2. target

1. SMI

2. tyrosine kinase, ALK, IGF1, and ROS1

Alectinib

1. class

2. target

1. SMI

2. ALK and RET

Lorlatinib

1. class

2. target

1. SMI

2. ALK and ROS1

Brigatinib

1. class

2. target

1. SMI

2. ALK and ROS1

what proteins are considered molecular switches?

RAS

Dabrafenib

1. class

2. target

3. severe ADE

1. SMI

2. BRAF

3. carcinoma, hypotension, kidney failure

name the MEK inhibitor

Trametinib

Trametinib

1. class

2. target

3. ADE

1. SMI

2. MEK

3. rash, diarrhea, edema

name the CDK inhibitor

Palbociclib

name the PI3K inhibitor

Idelalisib

name the mTOR inhibitor

Everolimus

what pathway promotes growth / proliferation

RAS / MAPK

what pathway promotes survival (anti-apoptosis)

PI3K / AKT / mTOR

which pathway promotes the cell cycle division

CDK

name the proteins that are pro-apoptosis

BAD

NOXA

BAX

BAK

name the proteins that are anti-apoptosis

Bcl-2

Bcl-xl

Which of the following does not promotes apoptosis?

a. bcl-2

b. NOXA

c. BAD

d. BAK

a