Week 3: Combo therapy

Question 1

Name 3 ways we have not been able to cure more patients with chemotherapy?

Answer 1

Altered threshold for apoptosis, Drug avoidance mechanisms in the cancer cells, Toxicity of the drugs to the host

Question 2

Explain the apoptotic pathway?

Answer 2

BH3 inhibits Bcl-2, allowing Bak and Bax to bind, BID turns into tBID as well, cytochrome C leaks out of mitochondria, caspase 9 is cleaved, as well as many other caspases leading to PARP cleavage and apoptosis

Question 3

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

Answer 3

Venetoclax

Question 4

What is the MOA of venetoclax?

Answer 4

mimics the action of BH3 domain, inhibiting Bcl-2, promoting apoptosis

Question 5

What do you have to worry about with treatment with venetoclax?

Answer 5

It is so potent it will cause extensive tumor lysis syndrome, causing hyperkalemia

Question 6

What is the definition of a curative clinical intent?

Answer 6

Treatment will result in cure fraction of at least 5%

Question 7

What is the definition of control clinical intent?

Answer 7

treatment has a

Question 8

What is the definition of palliative care?

Answer 8

treatment is designed to alleviate symptoms or to pre-emptively address an issue that will reliably be morbid

Question 9

What is the catch-phrase of using combination regimens?

Answer 9

Using agents of different mechanistic classes “non-cross resistant”

Question 10

What is the MOA of bleomycin?

Answer 10

induces DNA strand breaks by uncertain mech

Question 11

What can be the fatal DLT of bleomycin?

Answer 11

Can cause pulmonary fibrosis that can be fatal

Question 12

What drug reliably causes pulmonary fibrosis?

Answer 12

Bleomycin

Question 13

Does Bleomycin cause myelosuppression?

Answer 13

very little

Question 14

What drugs are included in BEP and what’s the intent of this drug combo?

Answer 14

Bleomycine, etoposide, cisplatin; used for germ cell tumors with a clinical intent of curative 95% of the time

Question 15

What drugs are included in R-CHOP; whats the cure rate?

Answer 15

Rituximab, cytoxan, doxorubicin, vincristine, prednisone; 80% of the time

Question 16

What are the drugs included in ABVD? What the cure rate?

Answer 16

Doxorubicin, bleomycin, vinblastine, dacarbazine; 90%

Question 17

What are the drugs in 3+7? What is the cure rate?

Answer 17

Daunorubicin, Ara-C; 20-30%

Question 18

What is included in AC –> T; what is it used for?

Answer 18

Doxorubicin, cyclophosphamide, taxane; breast cancer

Question 19

What drug combines well with DNA damaging agents, including radiotherapy?

Answer 19

gemcitabine

Question 20

What are the most promising ways of delivering drugs directly to tumor cells?

Answer 20

liposomes, targeted liposomes, antibody-drug conjugates drugs within polymers

Question 21

What are some liposome features for drug delivery?

Answer 21

proteins on the surface, antibodies that are targeted to the tumor, peptides, carbs, and small molecules

Question 22

What are the positive and negatives for liposomal doxorubicin?

Answer 22

not as much cardiac depression, but more prone to cause hand/foot syndrome

Question 23

What are elements of an antibody-drug conjugate?

Answer 23

antibody that is specific for tumor-associated antigen, linker to the cytotoxic agent that is stable in circulation and releases the agent inside targeted cells, cytotoxic agents designed to kill cells when internalized

Question 24

What is the brentuximab- vedotic used to treat?

Answer 24

CD30 expressing lymphomas (hodgkin lymphomas)

Question 25

What is trastuzumab-maytansine used to treat?

Answer 25

breast cancers over-expressing Her2

Question 26

What is so promising about camptothecin recently?

Answer 26

found ways to turn it into nanoparticles that are much better at targeting cells, with a great survival curve

Question 27

What do liposomes show great promise in delivering to targeted tumors?

Answer 27

traditional drugs, DNA, shRNA and toxins