10) Chemotherapy Flashcards
What are the different levels of tumour spread?
Local - surrounding structures
Lymphatic - carcinoma
Blood - sarcoma
Implantation - mechanical spread of tumour cells e.g. in chest drain
What are some options for chemotherapy use in patients?
Primary treatment (radical)
Adjuvant
Neoadjuvant
Palliative
When is chemotherapy used as radical treatment?
Lymphomas and leukaemia
What is adjuvant therapy?
Post-op treatment in a patient at high risk of microscopic metastases
What is neoadjuvant therapy?
Primary treatment of patients with a clinically localised tumour, reduce size for easier removal
What is the fractional cell kill hypothesis?
Chemotherapy given in fractionated doses to minimise damage to normal cells as they have time to recover
Give examples of cytotoxic agent classes:
Antimetabolites
Alkylating agents
Intercalating agents
Spindle poisons
What is the mechanism of action of platinum compounds?
Platinated intra and interstrand adducts leading to inhibition of DNA synthesis
What is the mechanism of action of topoisomerase inhibitors?
Inhibit the toposiomerase enzyme that unravels supercoiled DNA. Induces strand breaks leading to apoptosis
What is the mechanism of action of anti-metabolites?
Interfere with purine and pyramidine synthesis
Describe the treatment, Xeloda (campecitabine):
Treatment that is only activated in the tumour to produce 5-FU
What is the mechanism of action of spindle poisons?
Inhibit polymerisation of spindle microtubules
Stimulate polymerisation and prevent depolymerisation of spindle microtubules
What is the aim of combination therapy?
To provide increased efficacy using drugs with different modes of action that require different mechanisms to become resistant
How is P-glycoprotein involved in resistance to chemotherapy?
Efflux of cytotoxic agents out of cells
What are some mechanisms of resistance to chemotherapy?
Enhanced repair of DNA lesions
Efflux of drug
Inactivation of agent in cell
Modified target
What are some examples of DNA repair pathways?
Base excision repair
Recombinational repair
Nucleotide excision repair
Mismatch repair
How can mismatch repair status be used in bowel cancer treatment?
Those with mismatch repair deficient bowel tumour don’t respond to adjuvant chemotherapy
How can PARP1 inhibitors be used in BRCA mutated patients?
Inhibiting PARP1 which repairs SSBs will increase double strand DNA damage (not repaired due to BRCA mutation) causing cancer cell death
Describe the use of hormone therapy in breast cancer:
Anti-oestrogen - tamoxifen
Aromatase inhibitors
LHRH agonists
Describe the use of hormone therapy in prostate cancer:
LHRH agonists
Anti-androgens
Oestrogens
What is the rationale behind biologically targeted therapy?
Exploiting differences between normal cells and tumour cells to specifically target them
What is the mechanism of action of imatinib?
Bcr-abl tyrosine kinase inhibitor - inhibits fusion protein
What is the mechanism of action of Herceptin?
Monoclonal antibody against HER2 that inhibits proliferation of cancer cells and flags them for destruction
What is the mechanism of action of cetuximab? When will it fail as a treatment?
Blocks EGFR dimerisation, preventing proliferation of cancer cells
If the KRAS gene is mutated, KRAS becomes active without EGFR activation
How can angiogenesis be targeted for inhibition?
Anti-VEGF antibodies
Anti-VEGFR antibodies
Soluble VEGFRs
What are some routes of administration for chemotherapy?
IV - PICC and Hickman line
Subcutaneous injection
Intralesional e.g. liver
What is the mechanism of action of ipilimumab?
Ipilimumab is a monoclonal antibody that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system
Why are aromatase inhibitors particularly useful in post-menopausal women?
They can only get oestrogen by aromatase enzyme
What is the mechanism of action of nivolumab?
Anti-PD1 that allows T cells to bind and kill cancer cells
