Cancer Chemo Flashcards
Neoplasm
Uncontrolled growth of cells
May or may not form tumors. Usually don’t.
Invasiveness
Movement of neoplastic cells to adj. tissues
Metastasis
Movement of neoplastic cells to distant tissues
Tx of neoplasia
Surgery (solid tumor)
Radiation therapy (disrupt DNA of abnormal cells)
Pharmacologic agents (usually adjunct but sometimes primary modality)
Non-specific vs cell cycle specific agents
What about newer agents?
Non-specific
Act on cell in all phases of replication and resting-all cells
Form covalent bonds w/ all cell DNA
Prevent DNA cell fxn
Cell cycle specific
Act on cells replicating rapidly
Act on more defined sites
Anti-metabolites, enzyme inh, mitotic spindle inh.
Newer agents
Very specific
Kinase inh-“nibs”
Monoclonal antibodies-“nabs”
Alkylating agents
Names and mech.
Cyclophosphamide
Lomustine
Cisplatin
Mech
- Add alkyl group to DNA
- Causes DNA cross linking, inhibits cell replication, and RNA synth
- Non specific
- Inhibit non-replicating tumor cells
- Worry about extravasation-leakage into surrounding tissue
Cyclophosphamide
Tx: Cancer
Mech: Alkylating agent
- Add alkyl group to DNA
- Causes DNA cross linking, inhibits cell replication, and RNA synth
Nitrogen mustard
Developed from mustard gas-destroys everything it touches
Prodrug given orally or IV
Stops cell from replicating once it hits DNA
Lots of collateral damage
Lomustine
Tx: Cancer
Mech: Alkylating agent
- Add alkyl group to DNA
- Causes DNA cross linking, inhibits cell replication, and RNA synth
Prodrug given IV
Cisplatin
Tx: Cancer
Mech: Alkylating agent
- Add alkyl group to DNA
- Causes DNA cross linking, inhibits cell replication, and RNA synth
Contains platinum (expensive)
Associated w/ renal damage and ototoxicity
Doxorubicin
And other rubicins
Tx: Cancer
Mech: Intercalates w/ DNA→blocks DNA and RNA synth
Produces free radicals→break down DNA strands
Class: Antibiotic (produced by microorganisms)
SE:
- Can cause heart m. degeneration
- Irr. due to free radicals
- Fall in love w/ Ruby but she’s a free radical and breaks your heart.*
- Rubicin. Causes free radicals–> heart damage. Breaks DNA*
Dactinomycin
Tx: Cancer
Mech: Intercalates w/ DNA and interferes w/ mRNA synth
Bleomycin
Tx: Cancer
Mech: Intercalates w/ DNA-causes DNA strand breakage
SE: pulmonary fibrosis
_Bl_eo_my_cin _bl_ows my DNA apart
_Bleo_mycin affects your ability to blow (Pulmonary fibrosis)
Methotrexate
Tx: Cancer (and RA and psoriasis)
Mech:
- Analog of Folic Acid
- Inh. enzyme: Dihydrofolate reductase
- PABA→Folic acid⇒Dihydrofolic acid⇒tetrahydrofolic acid
- ⇒ indicate where DHFR works
SE:
- Myelosuppression-inh. of blood cells
- Can be dealt w/ by giving leucovorin-THFA analog
- Does not require DHFR
- Will rescue “normal” cells, but not malignant cells
- Can be dealt w/ by giving leucovorin-THFA analog
5-fluorouracil
Tx: Cancer
Mech: Inh. thymidylate synthatase→inh. thymidine synth
Prodrug–Pyrimidine analog
cytarabine
Tx: Cancer
Mech: Inh. DNA polymerase
Prodrug–Pyrimidine analog
6-mercaptopurine
Tx: Cancer
Mech: Converted in cell to an analog that inhibits several enzymes needed for purine synth
Prodrug–purine analog
- Azathioprine=immunosuppressant prodrug. *
- Gets converted into 6-mercaptopurine.*
- Used for Chron’s, RA, and transplants*
Vincristine and vinblastine
Tx: Cancer
Mech: Bind to microtubules and block cell mitosis
Route: IV
Natural product
Paclitaxel
and other “-taxel”s
Tx: Cancer
Mech: Forms abnormal microtubules
Natural-from western yew tree. But now purely synthetic
”-_t_axels” make _t_errible _t_ubules
Eribulin
Tx: Cancer
Mech: inh. microtubules-prevents mitosis, causes apoptosis
Fully synthetic
Ixabepilone
Tx: Cancer
Mech: Binds to microtubules
Natural product
- Ixabepilone *
- Pixabepilone*
- Pixy sticks=tube=microtubules*
- Yeah this one is a stretch…*
Etoposide
Tx: Cancer
Mech: Inhibits topoisomerase II→unrepairable DNA breaks
Natural product
- You know its a topoisomerase inhibitor but which one?*
- Add the first letter of one vs two to the front. If it makes sense it’s correct*
- Tetoposide vs oetoposide*
- **T-etoposide so topoisomerase Two***
Topotecan
and irinotecan
Tx: Cancer
Mech: inhibits topoisomerase 1
- You know its a topoisomerase inhibitor but which one?*
- Add the first letter of one vs two to the front. If it makes sense it’s correct*
- ttopotecan vs otopotecan*
- **O-topotecan so topoisomerase One***
Flutamide
and other “lutamides”
Tx: Cancer (prostate)
Mech: Blocks androgen receptor
Androgen receptor inside cell
Some tumors are hormone dependent
- Careful:*
- Flunomides-inh dihydroorate DH*
- Flutamides-block androgen receptor*
Abiraterone
Tx: Cancer (prostate)
Mech: Inhibits 17-hydroxylase lyase (CYP 17)
Inhibits androgen synthesis
Inhibits P450
- Get this man a beer, at least 17 sips, he can’t make any androgens.*
- Get this men abir-aterone, 17 CYP, can’t make any androgens*
- P450 inhibitors from this unit: Abiraterone and -flunomides*
Leuprolide
Tx: Cancer (prostate)
Mech: Activates GnRH receptor
Initially increases test synth, but eventually down regulates it
Used in comb. w/ other drugs
Lou Ferrigno was a pro bodybuilder w/ _AR_nold–initially boosted test. synth but eventually downregulated it
Leu-pro-lide _A_ctivates GnRH _R_eceptor–initially boosted test. synth but eventually downregulated it
Tamoxifen
Tx: Cancer
Mech: Blocks estrogen receptor
SE:
- Cataracts
- Retinal changes
Tammy is as big as an ox because her estrogen receptor is blocked. She’s obsessed w/ Ron Swanson and has CRazy eyes
Tamoxifen blocks estrogen receptor. Side effects associated w/ eyes: Cataracts and Retinal damage
Fulvestrant
Same as Tamoxifen
Tx: Cancer
Mech: Blocks estrogen receptor
SE:
- Cataracts
- Retinal changes
Anastrazole
Tx: Cancer
Mech: Inh. aromatase
Aromatase converts test→estr.
- Ana is strong b/c aromatase inh. so test can’t be converted to est. *
- Ana-stro-zole. Aromatase Inh so no conversion to est.*
- *Both of the estrogen blockers have a woman’s name and a reference to strength**
Tam-ox-ifen
Ana-stro-zole
Prednisone
Tx: Cancer-leukemias and lymphomas
Mech: Inh. immune system fxns (refer to other lecture)
SE: lots of them
Imitinib
Tx: Chronic myelogenous leukemia (CML)
Mech: Kinase inh.
In CML a gene codes for a kinase that shuts off apoptosis
So cells keep multiplying and don’t die=cancer
Imitinib inhibits the kinase so that apoptosis occurs again
Orally
SE: Edema (only a few SE)
-nib
Nib=inhibitor, usually of a kinase
Newer “nibs” inhibit specific pathways in cancer cells
Bortezomib
and carfilzomib
Tx: Multiply myeloma
Mech: Proteasome/protease inh.
Enzyme inhibitors
Allows excess proteins to accumulate and kill myeloma
“Zomibs” inh. proteaZomes
Trastuzumab
Tx: Cancer
Mech: vs HER2
Human epidermal growth factor receptor
- Don’t hook up w/ her too, that’s trashy*
- Don’t hook up w/ HER2, thats tras-tuzumab*
Bevacizumab
Tx: Cancer
Mech: blocks VEGF
Prevents Vascular epi. growth factor from binding to receptor
Tumor can only grow w/ blood supply-this blocks it
_Beave_rs are _veg_etarians
Beva-cizumab–VEGF
Rituximab
Tx: Chronic lymphocytic leukemia and RA
Mech: vs CD20
Ibritumomab
Tx: Cancer
Mouse MAB
Severe infusion rxn
Difficulties in treating neoplasia
- Not all cancer cells divide rapidly
- Normall cells are affected
- Hair
- Bone marrow
- GI
- Skin
- Oral mucosa
- Reproductive
Increase in renal and bladder tox.
Chemobrain
- Not all cancer cells killed by drug–may regrow
- Cancer cells can become resistant
- Drugs may not enter CNS–problem for brain cancer
- Alkylating agents may cause neoplasia
Successes w/ cancer
Curable (>5yr survival rate)
- Choriocarcinoma
- ALL
- Hodgkin’s lymphoma
- Testicular cancer
- Osteosarcoma
Greater success:
- Breast
- Ovarian
- Colon
- Multiple myeloma
Give larger doses early on
Better combinations
Prevent side effects (EPO w/ bone marrow loss)
