Chemotherapeutic Agents (Classic/Targeted, Drug Class, Example, MOA, AE)

Question 1

Alkylating Agents (Classic/Targeted, Drug Class, Example, MOA, AE)

Answer 1

Classic Agent

Example: Cyclophosphamide

MOA: Transfers alkyl group to DNA bases –> DNA damage –> induces apoptosis

AEs: Hemorrhagic Cystitis (caused by accumulation of drug metabolite that irritates bladder mucosa)
Second Malignancies
Gonadotoxic

TX: hydration + Mesna (taken before to neutralizes metabolite)

Question 2

Platinum Analogs (Classic/Targeted, Drug Class, Example, MOA, AE)

Answer 2

Classic Agent

Example: Cisplatin

MOA: binds/adducts DNA bases –> DNA damage –> induces apoptosis

AEs: Nephrotoxicity - taken in by proximal tubules
Neurotoxicity
Ototoxicity - due to transportation

Question 3

Antimetabolites (PURINE analogs) (Classic/Targeted, Drug Class, Example, MOA, AE)

Answer 3

Classic Agent

Example: 6-thioguanine (6-TG)

MOA: 6-TG is phosphorylated by HGPRT (hypoxanthine-guanine phosphoribosyltransferase) to 6-thioguanylic acid –> inhibiting purine biosynthesis (bc body is tricked into thinking theres too much) –> dec. DNA/RNA synthesis

AEs: Hepatotoxicity

**PRODRUG (activated in the body)

Question 4

Antimetabolites (PYRIMIDINE analogs)
(Classic/Targeted, Drug Class, Example, MOA, AE)

Answer 4

Classic Agent

Example: 5-fluorouracil (5-FU)

MOA: converted to F-dUMP –> binds/inhibits thymidylate synthase (which makes nucleotides for DNA)

AEs: Skin toxicity
Severe diarrhea

**PRODRUG (activated in the body)
***Needs THF to form complex for better binding

Leucovorin = source of THF; enhances 5-FU effects

Question 5

Antimetabolites (folate analogs) (Classic/Targeted, Drug Class, Example, MOA, AE)

Answer 5

Classic Agent

Example: Methotrexate (MTX)

MOA: inhibits DHFR (dec. [THF]) + also inhibiting purine biosynthesis (check 6-TG)

AEs: Pulmonary toxicity
Nephrotoxicity
Hepatotoxicity
TOXIC to embryo (they depend on THF)

Leucovorin = reduces/reverses MTX toxicity bc it provides THF

Question 6

Microtubule Inhibitors (Vinca Alkaloids)
(Classic/Targeted, Drug Class, Example, MOA, AE)

Answer 6

Classic Agent

Example: Vincristine

MOA: Blocks tubulin polymerization –> blocks mitosis

AEs: Neurotoxicity
Constipation

Question 7

Microtubules Inhibitors (Taxanes)
(Classic/Targeted, Drug Class, Example, MOA, AE)

Answer 7

Classic Agent

Example: Paclitaxel

MOA: blocks microtubule disassembly –> blocks mitosis

AEs: Neurotoxicity
Constipation

Question 8

Topoisomerase Inhibitors (Camptothecins)
(Classic/Targeted, Drug Class, Example, MOA, AE)

Answer 8

Classic Agent

Example: Topotecan

MOA: blocks re-ligation step of Topoisomerase 1 –> ss breaks –> ds breaks –> cell death

AEs: severe diarrhea

Question 9

Topoisomerase Inhibitors (Epipodophyllotoxins)
(Classic/Targeted, Drug Class, Example, MOA, AE)

Answer 9

Classic Agent

Example: Etoposide

MOA: blocks re-ligation step of Topoisomerase 2 –> ds breaks –> cell death

AEs: secondary leukemia due to chromosomal translocation

Question 10

Tyrosine Kinase Pathway Inhibitors - BCR-ABL Receptor
(Classic/Targeted, Drug Class, Example, MOA, AE, Use if targeted)

Answer 10

Targeted Agent

Example: Imatinib

MOA: blocks BCR-ABL RTK (enzymatic functions) by binding to ATP binding site

AEs: Fluid retention –> edema (swelling)

Use: Chronic myelogenous leukemia (CML)

Question 11

Tyrosine Kinase Pathway Inhibitors - EGF Receptor (intracellular)
(Classic/Targeted, Drug Class, Example, MOA, AE, Use)

Answer 11

Targeted Agent

Example: Erlotinib

MOA: blocks EGF receptor (in skin + lungs) by binding to ATP binding site

AEs: Skin rash
Pulmonary toxicity (in lungs)

Use: Lung cancer w/ mutated EGF receptor

Question 12

Tyrosine Kinase Pathway Inhibitors - VEGF Receptor
(Classic/Targeted, Drug Class, Example, MOA, AE)

Answer 12

Targeted Agent

Example: Sunitinib

MOA: blocks VEGF receptor (for blood flow/constriction) by binding to ATP binding sites

AEs: Hypertension
Increased thromboembolism
Increased bleeding

Use: Renal cancer (due to kidneys requiring a lot of blood)

Question 13

Tyrosine Kinase Pathway Inhibitors - BRAF
(Classic/Targeted, Drug Class, Example, MOA, AE)

Answer 13

Targeted Agent

Example: Vemurafenib

MOA: blocks mutant BRAF (not receptor)

AEs: skin squamous cell carcinoma

Use: Malignant melanoma w/ BRAF mutation

Question 14

Tyrosine Kinase Pathway Inhibitors - EGF Receptor (extracellular)
(Classic/Targeted, Drug Class, Example, MOA, AE)

Answer 14

Targeted Agent

Example: Cetuximab

MOA: monoclonal antibody to EGFR –> blocks EGF binding –> stimulates downregulation

AEs: Skin rash
Pulmonary toxicity

Use: Colorectal cancer (wildtype Ras/BRAF only)

Question 15

Steroid Receptor Antagonist - Androgen Receptor
(Classic/Targeted, Drug Class, Example, MOA, AE, Use)

Answer 15

Targeted Agent

Example: Flutamide

MOA: blocks androgen receptors in prostate gland –> decreases prostate growth

AEs: Decreased libido
Erectile dysfunction
Gynecomastia

Use: Metastatic prostate cancer

Question 16

Steroid Receptor Antagonist - Estrogen Receptor (SERM)
(Classic/Targeted, Drug Class, Example, MOA, AE)

Answer 16

Targeted Agent

Example: Tamoxifen

MOA: blocks estrogen receptors in breast tissue (and brain?) + stimulates ERs in bone/uterus/liver
(SELECTIVE)

AEs: Hot Flashes
Increased thromboembolism risk
Increased uterine cancer risk

Use: ER+ breast cancer

Question 17

Steroid Synthesis Inhibitors - Aromatase
(Classic/Targeted, Drug Class, Example, MOA, AE)

Answer 17

Targeted Agent

Example: Anastrozole

MOA: inhibits the enzyme aromatase (which stops estrogen synthesis)

AEs: Hot flashes
Increased risk of osteoporosis

Use: ER+ breast cancer