Cancer Chemotherapy Flashcards
What is the fractional cell kill hypothesis?
Use of pulses of chemotherapy
This allows the bone marrow time to recover before the next round of chemo
What is the site of action of antimetabolites?
DNA synthesis
What is the site of action of alkylating agents?
Interact with the DNA itself
Disrupting its structure
What is the site of action of intercalating agents?
They act on the DNA itself
Cause changes in the structure of DNA
Often cause frameshift mutations
What is the site of action of spindle poisons?
Name the two types and how they differ in their mechanisms
Disrupt microtubule dynamics
Vinca alkaloids: Inhibit polymerisation
Taxoids: Stimulate polymerisation + prevent depolymerisation
Name some of the post-translational modifications in DNA damage response
Phosphorylation
Ubiquitation
Sumolyation
Acetylation
If DNA damage levels are too high or persist, what are the two types of DNA damage repair response?
Senescence = permanent cell death
Apoptosis = controlled cell death
The ideal DNA damage repair response is what?
Repaired DNA damage to maintain cell function
What are the 4 main types of DNA damage repair pathway?
Base-excision repair (BER)
Nucleotide-excision repair (NER)
Recombinational repair (HR, EJ)
Mismatch repair
Under what circumstances of DNA damage might cells use base-excision repair (BER) ?
Uracil base
Abasic site
Single-strand break
Under what circumstances of DNA damage might cells use nucleotide-excision repair?
6-4 photoproducts
Bulky adducts
Under what circumstances of DNA damage might cells use recombinational repair (homologous recombination/ end-joining)?
Double-strand breaks
Interstrand cross-links
Under what circumstances of DNA damage might cells use mismatch repair?
A-G mismatch
T-C mismatch
Insertion
Deletion
Breifly explain how holliday junction resolution works to repair a double strand break
Generation of a heteroduplex region or resected DNA
Cleaved in two different ways to produce either two origional, repaired chromosomes or recombinants
What are the three main ways for cells to develop resistance against alkylating agents?
- Decreased entry or decreased exit of agent
- Inactivation of agent in cell
- Enhanced repair of DNA lesions produced by alkylation
What is a PICC line?
A peripherally inserted central line (venous access)
What is a Hickman line?
A skin-tunnelled, centralled inserted catheter
Protected from infection
Give some of the main side effects of chemotherapy
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
For which three factors might the dose of chemotherapy be altered?
Their surface area/BMI
Their drug handling ability (i.e. liver, renal function)
Their general wellbeing (comorbidities, performance status)
Abnormalities in which 4 factors can cause variability in the pharmacokinetics of chemotherapy agents?
- 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
Which drugs are it important to bear in mind in patients that are having chemotherapy?
Itraconazole (with Vincristine)
Warfarin (with Capecitabine)
Penicillin, NSAIDs (with Methotrexate)
St Johns Wort, grapefruit juice (with Capecitabine)
What kind of monitoring can we use during chemotherapy to assess patient response?
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
