Cancer Pharmacology

Question 1

Adjuvant therapy

Answer 1

Eradicate residual cancer AFTER primary surgery

Question 2

Neoadjuvant therapy

Answer 2

Shrink large, locally advanced disease to enable surgical resection

Question 3

Induction therapy

Answer 3

The first treatment given for a disease
-aims to achieve a rapid reduction in tumor burden or disease activity

Question 4

Consolidation therapy

Answer 4

Post-remission therapy to eradicate any remaining disease

Question 5

Maintenance therapy

Answer 5

Administered to prevent cancer from recurring

Question 6

Palliative therapy

Answer 6

Increase survival and improve quality of life by symptom control for advanced, incurable cancer

Question 7

Cycle

Answer 7

A period of chemotherapy treatment followed by a period of rest (holiday)

Question 8

What does the length of time between cycles depend on?

Answer 8

• May give therapy more frequently to enhance tumor effects BUT increases toxicity
• Balance with dose-limiting toxicities
• Also determined by pharmacokinetics of drugs

Question 9

Alkylating agents

Answer 9

• MOA: Via crosslinking guanine in DNA double-helix strands
• DNA damage
• Ex: Cyclophosphamide

Question 10

Antitumor Antibodies

Answer 10

• MOA: Via DNA intercalation
• DNA damage
• Ex: Anthracyclines (Doxorubicin - lymphoma, leukemia, breast, ovarian & Daunorubicin - leukemia), Bleomycin - lymphoma

Question 11

Topoisomerase inhibitors

Answer 11

• Blocks DNA strand re-ligation during DNA synthesis
• DNA synthesis
• Ex: Irinotecan

Question 12

Antimetabolites

Answer 12

• MOA: Are incorporated into DNA or RNA and inhibit nucleic acid synthesis
• DNA synthesis
• Ex: Folic acid, pyrimidine, or purine analogs - methotrexate, mercaptopurine, 5-FU

Question 13

Microtubule inhibitors

Answer 13

• MOA: Inhibit tubulin polymerization or function
• Translation/cell division
• Ex: Paclitaxel
• Breast cancer

Question 14

Nutrient deprivation

Answer 14

• MOA: Inhibition of protein synthesis
• Translation/cell division
• Ex: Asparaginase

Question 15

Hormonal agents

Answer 15

• MOA: Receptor antagonist. Attenuating estrogen/androgen production (growth signal)
• Targeted therapies (“go” signals)
• Ex: Tamoxifen, degarelix

Question 16

Epigenetic agents

Answer 16

-MOA:
* HDAC inhibitor - blocks deacetylation by HDAC and restores expression of tumor suppressor genes
* DNMT inhibitor - blocks methylation of promoters and restores expression of tumor suppressor genes
* Targeted signals (“go” signals)
* Ex: Vorinostat, azacitidine

Question 17

Angiogenesis inhibitors

Answer 17

• Target VGEF secreted by cancer cells or VEGFR
• Ex: Carfilzomib

Question 18

CDK4/6 inhibitors

Answer 18

• MOA: Prevents phosphorylation of Rb
• Ex: Ribociclib

Question 19

PARP inhibitors

Answer 19

• MOA: Prevents double-stranded DNA damage repair in BRCA-deficient cells
• Ex: Olaparib
• Activated by DNA damage

Question 20

What are the three groups of alkylating antineoplastic agents?

Answer 20

• Nitrogen mustards (cyclophosphamide)
• Nitrosoureas (carmustine)
• Non-classic alkylating agents (cisplatin)

Question 21

What is the mechanism of action of Anthracyclines?

Answer 21

Topoisomerase inhibitors

Question 22

Chromomycins

Answer 22

Binds to DNA and inhibit RNA translation

Question 23

Bleomycin

Answer 23

Induces DNA strand breaks

Question 24

Camptothecins

Answer 24

• Topoisomerases I inhibitor
• Inhibits strand resealing
• Irinotecan (colorectal, lung) and topotecan (ovarian)

Question 25

Epipodophyllotoxins

Answer 25

* Etoposide (lymphoma, lung, ovarian)

Question 26

What is the more detailed MOA of antimetabolites?

Answer 26

* Induce cell death during the **S phase of cell growth** when incorporated into RNA and DNA or inhibit **enzymes needed for nucleic acid production** * NOT selective for cancer cells

Question 27

Cytarabine (Ara-C)

Answer 27

Leukemias

Question 28

Fluorouracil (5-FU)

Answer 28

Colorectal cancer

Question 29

Capecitabine

Answer 29

Colorectal

Question 30

Gemcitabine

Answer 30

Lung, breast, and ovarian cancers

Question 31

Trifluridine and tipiracil

Answer 31

Colorectal cancer

Question 32

What are some microtubule inhibitors?

Answer 32

* Eribulin * Taxanes (Paclitaxel, cabazitaxel, docetaxel) * **Vinca Alkaloids (vincristine)**

Question 33

Eribulin

Answer 33

Breast cancer

Question 34

Taxanes (Paclitaxel, Cabazitaxel, Docetaxel)

Answer 34

Breast, lung, ovarian, and prostate cancer

Question 35

Vinca alkaloids (vincristine)

Answer 35

ALL, lymphoma, and lung cancer

Question 36

Epigenetics

Answer 36

Changes in gene expression that occur without altering DNA sequence

Question 37

CpG islands

Answer 37

CpG island are regions with a high frequency of CpG sites

Question 38

Histone modifications

Answer 38

A covalent post-translational modification to histone proteins which includes methylation and acetylation

Question 39

DNA methyltransferase (DNMT)

Answer 39

Enzymes that catalyze the transfer of a methyl group to DNA

Question 40

Histone acetyl transferase (HAT)

Answer 40

Enzymes that acetylate conserved **lysine amino acids** on histone proteins

Question 41

Histone deacetylase (HDAC)

Answer 41

Enzymes that remove acetyl groups

Question 42

What are the several stages in which signal transduction can be inhibited?

Answer 42

1. mAb against the growth factor receptor 2. mAb against a growth factor 3. Targeted drugs that inhibit intracellular kinases and prevent subsequent activation of downstream signals 4. Targeting downstream signals 5. Targeted therapies can be designed for mutated or WT protein

Question 43

What are the targeted therapies are available for tumors harboring certain mutations?

Answer 43

* Imatinib * Dastinib * Nilotinib * Ponatinib * Dabrafenib * Vemurafenib * Erlotinib * Afatinib * Gefitinib * Osimertinib * Lapatinib * Cetuximab * Panitumumab

Question 44

What is the G1 phase checkpoint regulated by?

Answer 44

Cyclin D1 and CDK4/6

Question 45

-tinib

Answer 45

tyrosine kinase inhibitor

Question 46

-zomib

Answer 46

proteosome inhibitor

Question 47

-ciclib

Answer 47

cyclin-dependent kinase inhibitor

Question 48

-parib

Answer 48

poly ADP-ribose polymerase inhibitor