Tx: Cancer Mech: _Alkylating agent_ Add alkyl group to DNA Causes DNA cross linking, inhibits cell replication, and RNA synth Prodrug given IV

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

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

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

Cancer Chemo Flashcards by Aaron Henley

Neoplasm

Uncontrolled growth of cells

May or may not form tumors. Usually don’t.

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Invasiveness

Movement of neoplastic cells to adj. tissues

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Metastasis

Movement of neoplastic cells to distant tissues

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Tx of neoplasia

Surgery (solid tumor)

Radiation therapy (disrupt DNA of abnormal cells)

Pharmacologic agents (usually adjunct but sometimes primary modality)

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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”

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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

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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

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Lomustine

Tx: Cancer

Mech: Alkylating agent

Add alkyl group to DNA
Causes DNA cross linking, inhibits cell replication, and RNA synth

Prodrug given IV

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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

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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*

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Dactinomycin

Tx: Cancer

Mech: Intercalates w/ DNA and interferes w/ mRNA synth

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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)

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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

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5-fluorouracil

Tx: Cancer

Mech: Inh. thymidylate synthatase→inh. thymidine synth

Prodrug–Pyrimidine analog

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cytarabine

Tx: Cancer

Mech: Inh. DNA polymerase

Prodrug–Pyrimidine analog

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6-mercaptopurine

Study These Flashcards

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

Study These Flashcards

Tx: Cancer

Mech: Bind to microtubules and block cell mitosis

Route: IV

Natural product

Paclitaxel

and other “-taxel”s

Study These Flashcards

Tx: Cancer

Mech: Forms abnormal microtubules

Natural-from western yew tree. But now purely synthetic

”-_t_axels” make _t_errible _t_ubules

Eribulin

Study These Flashcards

Tx: Cancer

Mech: inh. microtubules-prevents mitosis, causes apoptosis

Fully synthetic

Ixabepilone

Study These Flashcards

Tx: Cancer

Mech: Binds to microtubules

Natural product

Ixabepilone *
Pixabepilone*
Pixy sticks=tube=microtubules*
Yeah this one is a stretch…*

Etoposide

Study These Flashcards

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

Study These Flashcards

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”

Study These Flashcards

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

Study These Flashcards

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 **_CR_**azy _eyes_ _Tamoxifen_ _blocks estrogen receptor_. Side effects associated w/ _eyes_: **_C_**ataracts and **_R_**etinal 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 ## Footnote *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

1. Not all cancer cells divide rapidly 2. Normall cells are affected * Hair * Bone marrow * GI * Skin * Oral mucosa * Reproductive Increase in renal and bladder tox. Chemobrain 3. Not all cancer cells killed by drug--may regrow 4. Cancer cells can become resistant 5. Drugs may not enter CNS--problem for brain cancer 6. 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)

Cancer Chemo Flashcards

(38 cards)