Reverse Pharm Oncology

Question 1

Purine analogs which leads to decr. de novo purine synth

Activated by HGPRT

1 is metabolized into 6-MP

Preventing organ rejection
RA
IBD
SLE
Wean pts. off steroids
Treat steroid refractory chronic disease

Myelosuppresion
GI
LIver

1/2 metabolized by XO, so allopurinol and febuxostat incr. toxicity

Answer 1

azathioprine (1), 6 mercaptopurine (2), and 6 thioguanine

Question 2

Purine analog that has multiple mechanisms (strand breaks, inhibition of DNAP)

Hairy Cell Leukemia

Myelosuppression
Nephrotoxicity
Neurotoxicity

Answer 2

Cladribine (2 CDA)

Question 3

Pyrimidine analog leading to inhibition of DNAP

Leukemias (AML), lymphomas

Leukopenia
thrombocytopenia
megaloblastic anemia

Answer 3

Cytarabine

Question 4

Pyrimidine analog that Inhibits thymidylate synthase leading to decr. dTMP leading to decr. DNA

Colon cancer, pancreatic cancer, basal cell CA (topical)

Myelosuppresion (not reversible with leucovorin)

Answer 4

5FU

Question 5

Folic aid analog that competitively inhibits DHFR leading to decr. dTMP and decr. DNA synth

Cancers: Leukemias (ALL), lymphomas, chorioCA, Sarcomas

Ectopic pregnancy
Medical abortion (with misoprostol)
RA
Psoriasis
IBD
Vasculitis

Myelosuppresion (reversible with leucovorin)
Hepatotoxicity
Mucositis
Pulm. fibrosis

Answer 5

methotrexate

Question 6

Induces free radical formation lt breaks in DNA strands

Testicular cancer, Hodgkins lymphoma

Pulm. fibrosis, skin hyperpig, mucositis
Minimal myelosuppresion

Answer 6

Bleomycin

Question 7

intercalates in DNA

Wilms tumor
EWING sarcoma
rhabdomyosarcoma
childhood tumors (children ACT out)

Myelosupprsion

Answer 7

dactinomycin

Question 8

Generates free radicals
Intercalates in DNA lt breaks in DNA lt decr. replicaiton

Solid tumors, leukemias, lymphomas

Cardiotoxicity (dil cardiomyopathy)
myelosuppression
Alopecia

Dexrazoxane used to prevent CM

Answer 8

Doxorubicin and daunorubicin

Question 9

cross links DNA

CML
ablate patients bone marrow prior to transplant

Severe myelosuppresion (in almost all cases)
pulm. fibrosis
hyperpigmentation

Answer 9

Busulfan

Question 10

Cross link DNA at guanine N-7.
Bioactivation by liver

Solid tumors, leukemia, lymphomas

Myelosuppresion
Hemorrhagic cystitis

Answer 10

cyclophosphamide, ifofsamide

Question 11

Require bioactivation
Cross BBB
Cross link DNA

Brain tumors (including GBM)

CNS toxicity (convulsions, dizziness, ataxia)

Answer 11

nitrosoureas (carmustine, lomustine, semustine, streptozocin

Question 12

Hyperstabilizes microtubules in M phase so taht mitotic spindle cannot break down (anaphase cannot occur)
“It is taxing to stay polymerized”

Ovarian and breast CAs

Myelosuppresion
Alopecia
HSR

Answer 12

Paclitaxel

Question 13

Vinca alkaloids that bind beta tubulin and inhibit its polymerization into microtubules lt preventing of mitotic spindle formation

Solid tumors, leuk, HL (2), NHL (1), lymphomas

1=neurotoxicity (areflexia, periph neuritis, paralytic ileus)
2=myelosuppression

Answer 13

1-Vincristine

2=vinblastine

Question 14

Cross link DNA

Testicular, bladder, ovary, and lung CA

Nephrotoxicity, ototoxicity

Answer 14

cisplatin, carboplatin

Question 15

Inhibits topoisomerase II lt incr. DNA degradation

Solid tumors (test and Small Cell lung cancer)
leuk and lymph

myelosuppresion, GI upset, alopecia

Answer 15

etoposide, teniposide

Question 16

Inhibit topoisomerase I and prevent DNA unwinding and replication

Colon cancer-1
ovarian and small cell lung cancers-2

Severe myelosuppresion
Diarrhea

Answer 16

irinotecan (1), topotecan (2)

Question 17

Inhibits ribonucleotide reductase leading to decr. DNA synth

Melanoma, CML, Sickle cell disease (incr. HbF)

Severe myelosuppression
GI upset

Answer 17

hydroxyurea

Question 18

Various; bind intracytoplasmic receptor; alter gene transcription

Most commonly used glucocorticoids in cancer chemo
CLL, NHL
Immunosuppressants (auto immune)

Cushing like symptoms: weight gain, central obesity, muscle breakdown, cataracts, acne, osteoporosis, hypertension, peptic ulcers, hyperglycemia, psychosis

Answer 18

prednisone, prednisolone

Question 19

MAB against VEGF. Inhibits angiogenesis

Solid tumors (CRC, RCC)

Hemorrhage, blood clots, impaired wound healing

Answer 19

bevacizumab

Question 20

EGFR tyrosine kinase inhibitor

Non-small cell CA

Rash

Answer 20

erlotinib

Question 21

Tyrosine kinase inhibitor of BCR-ABL (CML; 9;22) and c-kit (GIST)

CML, GIST

Fluid retention

Answer 21

imatinib

Question 22

MAB against CD20, found in most b cell neoplasms

NHL, CLL, IBD, RA

Incr. risk of progressive multifocal leukoencephalopathy (JC virus)

Answer 22

rituximab

Question 23

SERMs-receptor antag in breast and agonists in bone
Block binding of estrogen to ER + cells

1=Breast cancer treatment and prevention
2=prevent osteoporosis

1=partial agonist in endometrium, which incr. risk of endometrial cancer; hot flashes
2=no incr. in endometrial CA b/c it is an antag there

Answer 23

tamoxifen (1), raloxifene (2)

Question 24

MAB against HER-2, and tyr kin receptor
Kills cancer cells that overexpress HER-2 through inhibition of HER-2 initiated cellular signaling and antibody dependent cytotoxicity.

HER-2 + breast cancer and gastric cancer

Cardiotoxicity

Answer 24

trastuzumab (herceptin)

Question 25

small molecule inhibitor of BRAF oncogene + melanoma

Metastatic melanoma

Answer 25

vemurafenib