Chemotherapy Flashcards
What drugs treat cancer?
- cytotoxic chemotherapy
- PARP inhibitors
- tyrosine kinase inhibitors
- monoclonal antibodies
- mTOR inhibitors
- immune checkpoint inhibitors
- CDK4/6 inhibitors
What is the growth fraction of tumours?
Proportion of cells dividing at any given time
- useful indicator of sensitivity to chemotherapeutic agents
- more responsive tumours have larger growth fractions
What is the fractional cell kill hypothesis?
- a given dose kills a constant proportion of tumour cells rather than number of tumour cells
- so repeated doses are required
What is adjuvant chemotherapy?
Chemo given after surgery to remove any remaining cells
What is neoadjuvant chemotherapy?
Chemo given before surgery to reduce tumour size
Relationship between tumour size + growth fraction
The bigger tumour, the smaller the growth fraction
This means less actively dividing cells to be dividing by chemo
Tumours that are highly chemo sensitive
Lymphomas
Germ cell tumours
Small cell lung
Neuroblastoma
Tumours that are modestly chemo sensitive
Breast
Colorectal
Bladder
Ovary
Cervix
Tumours that are lowly chemo sensitive
Prostate
Renal cell
Brain tumours
Endometrial
6 properties of cancer
- sustained angiogenesis
- limitless replicative potential
- tissue invasion + metastasis
- insensitivity to anti growth signals
- self sufficiency in growth signals
- evading apoptosis
What is the mechanism of action of alkylating agents
- alkyl groups on drug can form covalent bonds with cell constituent > inter strand cross linking
- DNA helix can’t unwrap + replicate
Examples of alkylating agents
Cisplatin
Oxaliplatin
What are uses of alkylating agents?
Malignancy
Adverse effects of chemotherapy
- alopecia
- mucositis
- N+V
- cardio toxicity
- diarrhoea
- cystitis
- infertility
- renal failure
- local reaction
- pulmonary fibrosis
- myelosuppression
Types of spindle poisons + example
- vinca alkaloids: vincristine
- taxanes: paclitaxel
What is the mechanism of action of spindle poisons
- vinca alkaloids: prevent spindle formation by inhibition of depolymerisation - microtubule assembly inhibitor e.g. vincristine
- taxoids: prevent disassembly + promote assembly - microtubule depolymerisation inhibitor e.g. paclitaxel
Examples of antimetabolites
5-fluorouracil
Methotrexate
What is the mechanism of action of 5-fluorouracil?
Inhibition thymidylate synthase
Prevents DNA production
What is the mechanism of action of methotrexate in malignancy?
- Dihydrofolate reductase inhibition
- Interrupts folate cycle
- reduction of thymine production
- reduces DNA production
Mechanisms of cancer cell resistance
- decrease uptake of drug
- increased drug metabolism
- alter drug targets
- impair apoptotic pathways
- alter cell cycle checkpoints
- efflux pumps
What is chemotherapy?
Treatment of cancer with cytotoxic drugs
What is salvage chemo?
Chemo for relapsed disease
What is palliative chemo?
To treat current or anticipated symptoms without the intention to cure
