Targeted Therapies

Question 1

What is a Philadelphia chromosome?

Answer 1

Results in a fusion protein tyrosine kinase that drives CML

Question 2

What percentage of most cancers are due to identifiable cancer susceptibility genes?

Answer 2

5-10% are genetic, heredited

Question 3

Which BRCA gene is most commonly mutated in African Americans?

Answer 3

BRCA II (Jews- BRCA1)

Question 4

What mutation would lead to GIST?

Answer 4

upregulation of c-kit which acts mainly via the RAS/RAF/MEK/ERK pathway

can treat with Gleevec

symptoms: decreased appetite, early satiety, and need to expand his belt.

Question 5

What is c-kit? Pathway?

Answer 5

transmembrane receptor that is activated by the ligand ScF (stem cell factor)

acts through RAS/RAF/MEK/ERk and also produces AKT which helps dissociate APC from B-catenin so it can enter the nucleus

Question 6

Fact about metastatic lung cancer.

Answer 6

In some patients pill produce better responses than intravenous drugs

5 yr survival rate about 2%

Once in the brain, it can be cured.

Asians and Americans have a different disease

Question 7

EGFR kinase mutation is common in which cancers?

Answer 7

lung cancer. Upregulated

Activating mutations present in 5% smokers, 15% non smokers, and 50% never smokers with adenocarcinoma

Question 8

Risk factors for EGFR mutations?

Answer 8

female, young, Asian, non-smoker

Question 9

How could you treat EGFR mutation?

Answer 9

Erlotinib (Tarceva)

Question 10

EML4-ALK fusion mutation causes what?

Answer 10

adenocarcinoma lung cancer

present in about 5% of lung cancers

Question 11

Risk factors for EML4-ALK mutation?

Answer 11

increased in never smokers, Asian, females

Question 12

How would you treat a EML4-ALK mutation?

Answer 12

Crizotinib- 57% response- better than chemo

Question 13

Describe the EGFR pathway.

Answer 13

Ligand (EGF, TGFa) bind to receptor, causing it dimerize and act via a JAK/STAT pathway to promote cell growth and proliferation

mutated (from hereditary or smoking, etc.)= over-expressed=tumor risk

Question 14

What drug can block ligand binding to EGFR?

Answer 14

Cetuximab (monoclonal antibody)

Question 15

What drug can prevent autophosphorylation of JAK?

Answer 15

Geftinib

Question 16

Facts about brain cancer.

Answer 16

Not all are fatal

There are 4 WHO grades of gilomas

gliomas are the most common brain neoplasm

Question 17

What are the most common brain neoplasms?

Answer 17

gilomas

WHO Grade I-II considered benign, Grade III-IV considered malignant.

Grade IV= giloblastoma (looks like a single ring-enhancing lesion)

Question 18

How does VEGF-A work?

Answer 18

via a VEGFR2 receptor (on vessel walls) and RAS/RAF/MEK/ERK pathway that causes cell proliferation and blood vessel formation

Question 19

How can VEGF be prevented from binding to mutated, over-expressed VEGF receptors?

Answer 19

Bevacizumab (Avastin)

Question 20

What does Sunitinib do?

Answer 20

used in renal cancer to block auto-phosphorylation of JAK in VEGF pathway

Question 21

What medicine can block an estrogen receptor?

Answer 21

Tamoxifen

Question 22

What is Everolimus?

Answer 22

mtor inhibitor that can be added to tamoxifen in hormone therapy failure in metastatic breast cancer

Question 23

What is Trastuzumab?

Answer 23

can block the HER-2 NEU receptor in breast cancer

Question 24

What is the pathway used in prostate regulation?

Answer 24

androgen pathway. ligand is testosterone

Question 25

What drug blocks androgen receptors?

Answer 25

Enzalutamide (Zytiga)

Question 26

What does Vemurafenib treat?

Answer 26

BRAF V600E/K mutation common in melanomas

Question 27

What is a hedgehog inhibitor?

Answer 27

Vismodegib