TyChucks Cancer Chemo Cards Flashcards
Drug combo that treats HER2 (increased aggressiveness) overexpression profile in breast cancer:
1) Blocks receptor action
2) Blocks receptor dimerization
1) Action blocking - trastuzumab
2) Dimer blocking - Pertuxumab
Some patients have an abnormally active tyrosine kinase driving proliferation… What tyrosine kinase inhibitors should be used for specific neoplasms?
Imatinib for chronic myeloid leukemia
Gefitinib for non-small cell lung cancer (Epidermal growth factor TK) – screen for specific EGFR mutation profile to see if you’re in 10% that responds extremely well to Gefitinib TK inhibitor
Inhibitors of angiogenesis
1) Bevacizumab - mAb against VEGF
2) Sunitinib - TK inhibitor of VEGF (also sorafenib)
Suberoylanilide Hydroxamic Acid
Epigenetics: it’s a histone deacetylase inhibitor (HDACi) keeping DNA transcriptionally active so that down-regulated tumor suppressor genes will be re-activated
Azacytidine & Decitabine
EpiG: inhibit methylation; thus reactivating innappropriately silenced tumor suppressor genes
Methylguanine Methyltransferase (MGMT)
EpiG: MGMT repairs alkylating damage to DNA; theory…methylate MGMT and treat with Temozolomide (alkylating agent) to induce damage and prevent repair
High levels of this metabolite in urine are associated with an increased invasion and metastasis
Sarcosine
Drug to prevent chemotherapy-induced side effects of headache, dizziness, diarrhea, and constipation
Serotonin Receptor Antagonist (Dolasetron & Palonosetron)
MOA of alkylating agents
covalently bind DNA and alter their structure and function… thus NON cycle-active
Name the (5) alkylating agents
Chlorambacil Cyclophosphamide Carmustin (BCNU) Busulfan Mechlorethamine
Important chemo drug for chronic leukemias (hint: its also the least toxic alkylating agent)
Chlorambucil
Requires metabolism to be active; alkylating agent
Cyclophosphamide
lipid soluble alkylating agent (thus great for CNS tumors)
Carmustin (BCNU)
alkylating agents used primarily for myelosuppression
Busulfan
Non-alkylating, non-cycle active drug that inhibits DNA synthesis and alters template activity… effective against a variety of solid tumors
Gemcitabine
Cancer drug analogous to trimethoprim (ie both used to inhibit dihydrofolate reductase thus stopping folic acid synthesis)… gets metabolized by adding glucuronic acid thus making it more water soluble and trapping it intracellularly
methotrexate
Used to “rescue” especially bone marrow during methotrexate-induced toxicity
folinic acid
Antimetabolites
methotrexate
purine analogues
pyrimidine analogues
***ALL DNA analogues MUST be metabolized to “nucleoside monophosphate” level to be incorporated into cell cycle
Purine Analogues
6-mercaptopurine
thioguanine
hydroxyurea
Pyrimidine Analogues
5-FU
cytarabine
MOA of 5-FU
inhibits thymidylate synthetase enzyme required to make thymidine monophosphate
Natural Products to treat cancer
Paclitaxel (taxol)* vincristine* vinblastine * etoposide toptecan
- = blocks mitosis!!!
Vincristine
remission, acute leukemia
advantage = minimal myelo suppression
Vinblastine
solid tumors, Hodgkins disease, testicular tumors
adv = less neuro toxic
disadv = myelosuppressive
Natural chemo drugs (2 of em) analogous to fluoroquinolones and their specific cancer uses
MOA: inhibit topoisomerases ===> DNA strand break
1) etoposide for testicular cancer
2) topotecan for ovarian and lung cancer
List the 4 natural antibiotics that act as cancer chemo drugs
1) doxorubicin
2) actinomycin D
3) Bleomycin
4) Mitomycin
natural antibiotic… inhibits RNA polymerase; non-cycle active… VERY toxic
Actinomycin D
natural antibiotic… mix of drugs that breaks DNA strands… NON-cycle active… unique toxicity = pulmonary fibrosis
Bleomycin
natural antibiotic that inhibits topoisomerases… thus is cycle-active… and cardiotoxic ===> arrythmias and CHF
Doxorubicin
natural antibiotic that is an alkylating agent… works against solid tumors
Mitomycin
Tamoxifen
Metabolized via CYP2D6 in the liver to endoxifen…. this MUST occur to be active
IF pt is taking another drug metabolized by cyp2d6 (ie anti-depressants like paxil, prozac…) this metabolism will be slowed down and it won’t be as effective
**MOA = anti-estrogen!!! ***
Exemestane & Anastrozole
MOA = aromatase inhibitors
thus aid in ER+ breast cancers… because they inhibit formation of estrogen to slow the proliferation that is typically induced by estrogen in such cancers
oral antiandrogen that prolongs life especially in men with metastatic prostate cancer
Flutamide
MOA = blocks uptake of androgens
MUST be given with leutinizing hormone releasing hormone analogue (ie leuprolide)
Platinum-containing drug that works similiarly to alkylating agens by causing DNA breaks… severe nephrotoxicity
Cis”plat”in – discovered at MSU
Cycle-active drug that inhibits ribonucleotide reductase resulting in an inhibition to go for ribo to deoxyribo…. thus inhibiting BOTH purine and pyrimidine synthesis
Hydroxyurea!
why is there typically an outgrowth of resistant subpopulations? (don’t overthink it)
tumors are heterogeneous… and any cells within the tumor that are resistant (which is likely) will survive to re-populate a new tumor that is unaffected by such treatment
