Cancer Therapy

Question 1

What are the two types of radiotherapy?

Answer 1

• radical type: for curing

- palliative type: for symptom relief

Question 2

Adjuvant Chemotherapy

Answer 2

• used after successful surgical resection (post-op)

- kills any micrometastases to prevent recurrence

Question 3

Neoadjuvant Chemotherapy

Answer 3

• used before surgery (pre-op)

- decreases tumor size; makes the surgery easier

Question 4

Are there any cells that are relatively insensitive to chemo?

Answer 4

• yes, quiescent cells in G0 and hypoxic cells

Question 5

What does chemotherapy target?

Answer 5

• the DNA of rapidly-dividing / highly-active cells (cancer cells)
• normal cells are also affected

Question 6

Antitumor Antibiotics

Answer 6

• natural products isolated from fungi in the soil (such as Streptomyces sp.)
• form complexes with DNA, preventing replication
• non cell cycle specific

Question 7

Antimetabolites (2 subgroups)

Answer 7

• interfere with the incorporation of nucleotides into DNA
• cell cycle specific (S phase)
• 1) nucleotide analogs (can resemble purines or pyrimidines)
• 2) antifolates: inhibit folic acid, which is needed for biosynthesis of amino acids and nucleotides

Question 8

Alkylating Agents

Answer 8

• form unstable alkyl groups that react with e- rich sites (nucleic acids, DNA); basically, they attach alkyl groups to DNA
• non cell cycle specific
• tend to target rapidly proliferating tissues

Question 9

Platinum Analogs

Answer 9

• grouped in with alkylating agents because of similar mechanism

Question 10

Antimicrotubular Agents (4 subgroups)

Answer 10

• disrupt microtubules, arresting mitotic cell division
• cell cycle specific (M phase)
• 1) taxanes, 2) vinca alkaloids, 3) halichondran B analog, 4) epothilanes

Question 11

Topoisomerase Inhibitors

Answer 11

• stabilize topoisomerase-DNA complexes, preventing repair of the DNA breaks the complex made
• cell cycle specific (S phase)

Question 12

How does Topoisomerase function?

Answer 12

• forms a temporary complex with DNA and then breaks the DNA at certain points to prevent tangling during replication; these breaks are quickly repaired once the protein leaves

Question 13

Irinotecan

Answer 13

• a topoisomerase I inhibitor
• a pro-drug that needs to be activated in the liver by carboxylesterase
• activated form = SN-38

Question 14

Which normal tissues are most affected by chemotherapy?

Answer 14

• cells of the GIT and bone marrow, because they are actively dividing and metabolic

Question 15

Myelosuppression

Answer 15

• bone-marrow suppression
• a major toxicity issue of chemotherapy
• chemo results in immunosuppression due to neutropenia and leukopenia

Question 16

What is Endocrine Therapy?

Answer 16

• exogenous administration of hormones to control cancer

- is the mainstay therapy for breast and prostate cancers

Question 17

TKIs

Answer 17

• (small molecule) Tyrosine Kinase Inhibitors
• bind to epidermal growth factor receptors (EGFRs) of cancer cells and prevent the initiation of the signal cascade that would normally trigger proliferation

Question 18

Cetuximab & Panitumumab

Answer 18

• monoclonal antibodies that competitively inhibit EGFR binding to its ligand, preventing the signaling for growth

Question 19

What is the idea behind cancer immunotherapy?

Answer 19

• to tip the balance from tolerance for cancer cells to activation against them

Question 20

CTLA-4

Answer 20

• Cytotoxic T Lymphocyte Antigen-4
• induces tolerance of the cell expressing it
• cancer cells produce an over abundance of CTLA-4

Question 21

PD-1

Answer 21

• Programmed Death-1

- inhibits T-cell activation against cells expressing it

Question 22

Nivolumab

Answer 22

• inhibits PD-1, allowing an immune response to attack the target cells

Question 23

Ipilimumab

Answer 23

• blocks CTLA-4, removing immune tolerance for the target cells and allowing attack