Week 3: Combo therapy Flashcards
Name 3 ways we have not been able to cure more patients with chemotherapy?
Altered threshold for apoptosis, Drug avoidance mechanisms in the cancer cells, Toxicity of the drugs to the host
Explain the apoptotic pathway?
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
What was the first drug to target Bcl-2 in order to restore pro-apoptotic signals
Venetoclax
What is the MOA of venetoclax?
mimics the action of BH3 domain, inhibiting Bcl-2, promoting apoptosis
What do you have to worry about with treatment with venetoclax?
It is so potent it will cause extensive tumor lysis syndrome, causing hyperkalemia
What is the definition of a curative clinical intent?
Treatment will result in cure fraction of at least 5%
What is the definition of control clinical intent?
treatment has a
What is the definition of palliative care?
treatment is designed to alleviate symptoms or to pre-emptively address an issue that will reliably be morbid
What is the catch-phrase of using combination regimens?
Using agents of different mechanistic classes “non-cross resistant”
What is the MOA of bleomycin?
induces DNA strand breaks by uncertain mech
What can be the fatal DLT of bleomycin?
Can cause pulmonary fibrosis that can be fatal
What drug reliably causes pulmonary fibrosis?
Bleomycin
Does Bleomycin cause myelosuppression?
very little
What drugs are included in BEP and what’s the intent of this drug combo?
Bleomycine, etoposide, cisplatin; used for germ cell tumors with a clinical intent of curative 95% of the time
What drugs are included in R-CHOP; whats the cure rate?
Rituximab, cytoxan, doxorubicin, vincristine, prednisone; 80% of the time
What are the drugs included in ABVD? What the cure rate?
Doxorubicin, bleomycin, vinblastine, dacarbazine; 90%
What are the drugs in 3+7? What is the cure rate?
Daunorubicin, Ara-C; 20-30%
What is included in AC –> T; what is it used for?
Doxorubicin, cyclophosphamide, taxane; breast cancer
What drug combines well with DNA damaging agents, including radiotherapy?
gemcitabine
What are the most promising ways of delivering drugs directly to tumor cells?
liposomes, targeted liposomes, antibody-drug conjugates drugs within polymers
What are some liposome features for drug delivery?
proteins on the surface, antibodies that are targeted to the tumor, peptides, carbs, and small molecules
What are the positive and negatives for liposomal doxorubicin?
not as much cardiac depression, but more prone to cause hand/foot syndrome
What are elements of an antibody-drug conjugate?
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
What is the brentuximab- vedotic used to treat?
CD30 expressing lymphomas (hodgkin lymphomas)
What is trastuzumab-maytansine used to treat?
breast cancers over-expressing Her2
What is so promising about camptothecin recently?
found ways to turn it into nanoparticles that are much better at targeting cells, with a great survival curve
What do liposomes show great promise in delivering to targeted tumors?
traditional drugs, DNA, shRNA and toxins
