Anticancer agents

Question 1

Cancer statistics

Answer 1

Major cause of death in pets (40-45% of all dogs >10 yrs of age)
23% of all dogs die of cancer

Question 2

Hallmarks of cancer

Answer 2

Sustaining proliferative signaling
Evading growth suppression
Resisting cell death
Inducing angiogenesis
Enabling replicative immortality
Activating invasion and metastasis

Question 3

Treating cancer

Answer 3

Surgery
Radiation therapy
Chemmotherapy
Hyperthermia
Photodynamic therapy

Question 4

Chemotherapy

Answer 4

Mono-therapy for systemic cancers
Adjuvant therapies
Neo-adjuvant therapies (prior to surgery to shrink tumor)

Question 5

Chemotherapy activation of immune system

Answer 5

Activates macros, T cells and monos → release pro-inflammatory and activation of apaptotic pathways → cell death

Question 6

Chemotherapy on microtubules

Answer 6

Vincristine inhibition of microtubule aggreggation and Paclitaxel inhibition of microtubule disaggregation → altered function of microtubules → cell arrest

Question 7

Chemotherapy on the nucleus

Answer 7

Oxaliplatin, cisplatin inhibition of DNA replication and mRNA transcription → DNA/RNA polymerase → cell arrest and death

Question 8

Chemotherapy on the mitochondria

Answer 8

Oxaliplatin, cisplatin, Vincristine, pacliaxel alter function of resp. chain→ ↑ ROS
OR
→ altered mitochondrial function → activation of apoptosis

Question 9

Sustained proliferation

Answer 9

Replicative immortality
Cancer cells constantly divide and cycle

Question 10

What are the subclasses of alkalizing agents?

Answer 10

Nitrogen mustards
Nitrosoureas
Alkyl sulphonates
Atypical

Question 11

Alkalizing agents MOA

Answer 11

Add alkyl group to the N7 atom of guanine base of the DNA molecule → cross linking of DNA and strand breaks

Question 12

Alkaline agents in the cell cycle

Answer 12

Binds to DNA in the S-phase

Question 13

Nitrogen mustards

Answer 13

Cyclophosphamide
Ifosfamide
Melphalan
Chlorambucil

Question 14

Ifofsamide

Answer 14

Isomer of Cyclophosphamide
Slow IV infusion
Toxicity: Neutropenia, hemorr. cystitis, CNS

Question 15

MESNA (Mesnex)

Answer 15

Rescue agent for hemorr. cystitis
Well tolerated, could cause N/V

Question 16

Cyclophosphamide

Answer 16

Most used nitrogen mustard in vet med
Prodrug given IV or oral
Lymphomas K9 and cats
Malignant mammary gland tumors

Question 17

Cyclophosphamide toxicity

Answer 17

Myelosuppression, alopecia, neutropenia, hemorr cystitis
GI (cats)
Bladder irritation

Question 18

Amelioration of Ifofsamide and Cyclophosphamide toxicity

Answer 18

Adequate hydration
Diuresis by IV furosemide
Co-admin of MESNA

Question 19

Melphalan

Answer 19

Orally and IV
Multiple myeloma in K9 and cats, plasma cells tumors, extramedullary plasmacytoma, relapsed lymphoma in K9

Question 20

The main side effect of melphalan is ____________

Answer 20

Myelosupression

Question 21

Chlorambucil (Leukran)

Answer 21

One of the most common
Slow acting and least toxic
PO on empty stomach of IV
Replace Cyclophosphamide to avoid hemorr. cystitis

Question 22

Chlorambucil toxicity

Answer 22

Myelosuppression with neutropenia and thrombocytopenia
Reversible BM suppression

Question 23

Chlorambucil uses

Answer 23

Slower growing tumors like Chronic lymphocytic leukemia, Small cell lymphoma, GI lymphoma in cats

Question 24

Anticancer ABX

Answer 24

Doxorubicin
Bleomycin
Mitoxantrone

Question 25

Doxorubicin MOA

Answer 25

From Streptomyces peucetius Intercalates to DNA, inhibits topoisomerase 2, interferes with RNA synthesis Produces free radicals Act on cells deficient in superoxide dismutase (cardiac and tumor cells)

Question 26

Doxorubicin uses

Answer 26

Most effective Lymphoma and leukemia of K9s and cats Combo with cyclophosphamide to treat lymphosarcoma in K9s and cats

Question 27

Doxorubicin toxicity

Answer 27

Cardiotoxicity is K9s Anorexia and nephrotoxicity in cats Palmer-planta erythrodysesthesia syndrome (treated with B6)

Question 28

Bleomycin

Answer 28

From S. verticillus IV, IM, SC Cell specific: G2 and M phase Treats squamous cell carcinoma

Question 29

Bleomycin toxicity

Answer 29

Causes cytoxicity by binding to DNA Pulmonary toxicity (rales, cough, fatal fibrosis)

Question 30

Mitoxantrone

Answer 30

Synthetic athracenedione Treats lymphoproliferative disorders (lymphomas and leukemias) Transitional cells carcinoma of urinary bladder

Question 31

Mitoxantrone toxicity

Answer 31

Extravasation necrosis Mild BM depression Bluish- green sclera and urine

Question 32

Antimetabolites

Answer 32

Prevents biosynthesis of cell metabolism S-phase specific Metabolized to active form Used for leukemias

Question 33

Antimetabolite drugs

Answer 33

Pteridines (methotrexate) Pyrimidine analogs (fluoroacil) Purine analogs (6- mercaptopurine)

Question 34

Methotrexate

Answer 34

Inihibits dihydrofolate reductase IV, IM, IV, oral Limited veterinary use

Question 35

Microtubule inhibitors and the cell cycle

Answer 35

Stope cell separation during division during the G2 phase

Question 36

Vinca alkaloids taxols and the cell cycle

Answer 36

Stop cell separation during divison during the M phase