Cancer 3 Flashcards
What are names of DNA intercalating agents?
- Dactinomycin
- Daunorubicin, Doxorubicin
- Bleomycin
DNA intercalating agents are also called
anti-tumor antibiotics, which are derived from various strains of the soil microbe Streptomyces
what is the mech of DNA intercalating agents?
bind to DNA through intercalation between specific bases and block synthesis of DNA, RNA, or both, cause DNA strands break, and interfere with cell replication
Dactinomycin is also known as
Actinomycin D
what is the mech of Dactinomycin (Actinomycin D)?
intercalates between G-C base pairs of DNA, forming stable dactinomycin-DNA complex. The complex interferes with DNA-dependent RNA polymerase causing inhibition of transcription of DNA
what is the main therapeutic uses of Dactinomycin?
to treat pediatric umors such as Wilms’ tumor, rhabdomyosarcoma and Ewing’s sracoma
what are antrhacycline antibiotics derived from Streptomyces that have a broad spectrum of clinical usefulness in hematologic and solid tumors?
Daunorubicin, Doxorubicin, Epirubicin, and Idarubicin
daunorubicin and idarubicin are mainly used for
AML treatment
what are the toxicity of - rubicin drugs?
irreversible does-limiting cardiotoxicity (cardiomyopathy)
what is a mixture of two copper-chelating peptides obtained from Streptomyces?
bleomycin
what is the mech of bleomycin?
in the presence of Fe and O2, it forms free radical and induce
what is the therapeutic usage of bleomycin?
testicular tumors (usually in combination with vinblastine or etoposide)
toxicity of bleomycin?
pulmonary toxicity (pulmonary fibrosis) cutaenous toxicity (hyperpigmentation)
what are the three monoclonal antibodies?
- Rituximab
- Trastuzumab (Herceptin)
- Cetuximab
what is useful for treating Non-Hodgkin’s lymphomas?
Rituximab
what is a monoclonal antibody that targets the CD20?
Rituximab
what are two tyrosine kinase inhibitors?
- Imatinib (Gleevac)
2. Gefitinib
what is an inhibitor of Abl kinase?
Imatinib
Imatinib also inhibits
PDGFR and c-kit and effective treating CML
Imatinib is approved for CML, but also approved for
gastrointestinal tumor
what are the miscellaneous agents used to treat cancer?
- Hydroxyurea
- Retinoids
- Arsenic Trioxide
- Thalidomide
- Interferons
what is the mech of hydroxyurea?
inhibits the enzyme ribonucleoside diphosphate reductase, which catalyze the conversion of ribonucleotides to deoxyribonucleotides (a critical rate limiting step in the biosynthesis of DNA)
what are the two therapeutic usage of hydroxyurea?
- sickle cell diz
2. myeloproliferative neoplasms polycythemia vera and thrombocythemia
what is all-trans retinoic acid (ATRA) what is useful for treating acute promyelocytic leukemia (APL)?
Retinoids
what is used for relapsed APL?
arsenic trioxide
what is used for treating multiple myeloma and myelodysplastic syndromes?
thalidomide
what is used for treating of hairy-cell leukemia, CML, and AIDS-related Kaposi’s sarcoma?
Interferons
what are the hormone therapies for prostate cancer?
- Leuprolide, Goserelin
2. Flutamide, Bicalutamide
what are gonadotropin-releasing hormone (GnRH) analogs?
Leuprolide, Goserelin
what is the mech for leuprolide?
GnRH analogs, they bind to GnRH receptor and inhibit the release of FSH and LH
as a result of leuprolide what happens?
reduced testicular production of testosterone
what are nonsteroidal androgen-receptor (AR) blockers?
flutamide, bicalutamide
what is the mech of AR blocker (flutamide)
compete with the natural hormone for binding to the androgen receptor and prevent its translocation to the nucleus
what is complete androgen ablation therapy?
it involves combination of GnRH analogs and AR blockers
what is aromatase enzyme?
conversion of androstenedione and testosterone to the estrogen, estrone and estradiol.
in breast cancer pts, there is increased
aromatase activity
what is the 1st generation AI?
aminoglutathamide
paclitaxel can cause what kind of toxicity?
peripheral neuropathy
what is a 3rd generation AI?
Anastrozole
what are selective estrogen-receptor downregulator?
pure anti-estrogens (they are devoid of estrogen agonist activity)
what is the name of SERDs drug?
Fulvestrant
what is Fulvestrant?
the 1st FDA approved SERDs, it binds to ER with much higher affinity (more than 100 fold) than tamoxifen
how is Fulvestrant diff from tamoxifen?
tamoxifen stabilizes or even increase ER expression, fulvestrant reduces the number of ER molecules in cells
what is therapeutic uses of Fulvestrant?
approved for postmenopausal women with ER-positive metastatic breast cancer
dactinomycin is also known as
Actinomycine
the main therapetuic uses of Dactinoomycin is
Wilm’s tumor, Ewing’s sarcoma in children
what are anthracyclines?
daunorubicin, doxorubicin, epirubicin, idarubicin
mech of action of anthracyclines (doxorubicin)?
intercalate between DNA base pairs, donate electrons to make superoxide
sarcomas treatment?
Doxorubicine
what is important about the side effect of anthracycline?
dose-limiting cardiotoxicity,
Dexrazoxone is an
iron-chelating agent that blocks the fomration of free radical
bleomycin is
a mixture of two peptides obtained from Streptomyces, G2 phase specific
therapeutic usage of bleomycin?
- squamous cell caricnomas, ABVD
toxicity of bleomycin?
- minimally myelosuppressive
2. dose-related pulmonary toxicity (pulmonary fibrosis)
microtubule inhibitos
vinca alkaloids, taxanes
mech of vinca?
prevent polymerization of tubulin into microtubules
what is the therapeutic usage of vinca alkaloids?
Vinblastine –> ABVD
Vincristine –> MOPP, used with glucocorticoids in the treatment of childhood ALL
what is the resistance mech of vinca?
P-glycoprotein, mutation in tubulin
what are taxanes?
paclitaxel, docetaxel
where are taxanes from?
alkaloids dervied from the ye tress
the mech of taxanes?
prevent the depolymerization of microtubules
docetaxel is useful against
hormone refractory prostate cancer
what are the toxicity of taxanes?
perepheral neuropathy
topoisomerase inhibitors?
- epipodophyllotoxins: etoposide, teniposide (top II)
2. camptothecin analgos: irinotecan, topotecan (top I)
epidophyllotoxins
inhibit topoisomerase II –> apoptosis
camptothecin analogs
inhibitn topoisomerase I –> apoptosis
hormone therapy is suefull in
lymphomas and leukemia, breast, prostate
glucocorticoids (prednisone, dexamethasone) are used for
lymphomas and leukemia
prednisone is used for
ALL, both Hodkin and non-Hodgkin
breast cancer is usually
estrogen dependent, so it can be suppressed by estrogen antagonist
SERMs
selective estrogen receptor modulators: Tamoxifen
tamoxifen is
a weak agonist in endometrium –> increase risk for endometrial cancer and thromboembolism
SERDs
selective estrogen-receptor downregulators: Fulvestrant
SERD, Fulvestrant
bins to ER with a much higher affinity (more than 100 fold) than tamoxifen
hydroxyurea inhibit
ribonucleotide reductase, for sickle cells
all trans-retinoic acid is for
APL = AML M3 –> promotes differentiation of promyelocyte
inteferone alpha
hairy cell leukemia, Kaposi’s sarcoma
Gefitinib
EGFR inhibitor
Cetuximab is a
mAb against ErbB1 for treatment of metastatic colon cancer
multi-drug resistance
P-glycoprotines –> drug efflux
what is verapamil?
Ca2+ channel antagonist, which inhibits these drug transporters
P-glyoprotein forms
a central channel for the ATP dependent pumping of drugs from the cell
what are the 3 toxicities of cisplatin?
- nephrotoxicity
- ototoxicity
- peripheral neuropathy
what are the 3 toxicities of methotrexate?
- renal toxicity
- hepatotoxicity
- bone marrow toxicity
toxicity of paclitaxel?
perepheral neuropathy
toxicity of vincristine?
neurotoxicity (peripheral neuropahty)
resistance to which anticancer drug is associated with decreased expression of hypoxanthine-guanine phosphoribosyl transferase (HGPRT)?
6-MP
