Cancer Chemotherapy

Question 1

What is the fractional cell kill hypothesis?

Answer 1

Use of pulses of chemotherapy

This allows the bone marrow time to recover before the next round of chemo

Question 2

What is the site of action of antimetabolites?

Answer 2

DNA synthesis

Question 3

What is the site of action of alkylating agents?

Answer 3

Interact with the DNA itself

Disrupting its structure

Question 4

What is the site of action of intercalating agents?

Answer 4

They act on the DNA itself

Cause changes in the structure of DNA

Often cause frameshift mutations

Question 5

What is the site of action of spindle poisons?

Name the two types and how they differ in their mechanisms

Answer 5

Disrupt microtubule dynamics

Vinca alkaloids: Inhibit polymerisation

Taxoids: Stimulate polymerisation + prevent depolymerisation

Question 6

Name some of the post-translational modifications in DNA damage response

Answer 6

Phosphorylation

Ubiquitation

Sumolyation

Acetylation

Question 7

If DNA damage levels are too high or persist, what are the two types of DNA damage repair response?

Answer 7

Senescence = permanent cell death

Apoptosis = controlled cell death

Question 8

The ideal DNA damage repair response is what?

Answer 8

Repaired DNA damage to maintain cell function

Question 9

What are the 4 main types of DNA damage repair pathway?

Answer 9

Base-excision repair (BER)

Nucleotide-excision repair (NER)

Recombinational repair (HR, EJ)

Mismatch repair

Question 10

Under what circumstances of DNA damage might cells use base-excision repair (BER) ?

Answer 10

Uracil base

Abasic site

Single-strand break

Question 11

Under what circumstances of DNA damage might cells use nucleotide-excision repair?

Answer 11

6-4 photoproducts

Bulky adducts

Question 12

Under what circumstances of DNA damage might cells use recombinational repair (homologous recombination/ end-joining)?

Answer 12

Double-strand breaks

Interstrand cross-links

Question 13

Under what circumstances of DNA damage might cells use mismatch repair?

Answer 13

A-G mismatch

T-C mismatch

Insertion

Deletion

Question 14

Breifly explain how holliday junction resolution works to repair a double strand break

Answer 14

Generation of a heteroduplex region or resected DNA

Cleaved in two different ways to produce either two origional, repaired chromosomes or recombinants

Question 15

What are the three main ways for cells to develop resistance against alkylating agents?

Answer 15

1. Decreased entry or decreased exit of agent
2. Inactivation of agent in cell
3. Enhanced repair of DNA lesions produced by alkylation

Question 16

What is a PICC line?

Answer 16

A peripherally inserted central line (venous access)

Question 17

What is a Hickman line?

Answer 17

A skin-tunnelled, centralled inserted catheter

Protected from infection

Question 18

Give some of the main side effects of chemotherapy

Answer 18

Actue renal failure - precipitation of urate in the kidneys

GI perforation @ tumour site

DIC

Vomiting (acute, delayed, chronic)

Alopecia

Skin toxicity (local and general)

Mucositis

Cardio-toxicity- arrhythmias

Lun-toxicity- pulmonary fibrosis

WBC depletion, platelet depletion, RBC depletion

Question 19

For which three factors might the dose of chemotherapy be altered?

Answer 19

Their surface area/BMI

Their drug handling ability (i.e. liver, renal function)

Their general wellbeing (comorbidities, performance status)

Question 20

Abnormalities in which 4 factors can cause variability in the pharmacokinetics of chemotherapy agents?

Answer 20

• Absorption: Nausea and vomiting, compliance, gut absorption
• Distribution: Weight loss, reduced body fat, ascites
• Elimination: Liver and renal dysfunction, drug-drug interactions
• Protein binding: Low albumin, drug-drug interactions

Question 21

Which drugs are it important to bear in mind in patients that are having chemotherapy?

Answer 21

Itraconazole (with Vincristine)

Warfarin (with Capecitabine)

Penicillin, NSAIDs (with Methotrexate)

St Johns Wort, grapefruit juice (with Capecitabine)

Question 22

What kind of monitoring can we use during chemotherapy to assess patient response?

Answer 22

Response of the cancer: radiological imaging, tumour marker bloods, bone marrow/cytogenetics

Drug levels: drug assays to ensure clearance

Check for organ damage: creatinine clearance, echo