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L32 - Treating Cancer Understand that chemotherapy is used in combination…
L32 - Treating Cancer
- Understand that chemotherapy is used in combination with other treatments to treat cancer
- Understand that classical cancer drugs act on highly proliferative tissues (i.e. not specific for cancer cells)
- Outline the general principles of classical chemotherapy
- Describe the mechanisms of action of the major classes of classical chemotherapeutic drugs
- List their likely & important side effects
- Describe how radiotherapy is used to treat cancer
- List how resistance to chemotherapy can arise*
Mechanisms of Anticancer Drugs
Traditionally drugs nduce apoptosis by interfering with cell function
- chemical damage to DNA → DNA adducts and strand crosslinking
- impaired synthesis of DNA bases - pyrimidines & purines
- inhibition of transcription or translation
- disruption of cell division mechanics -
e.g. impaired microtubule function*
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Side Effects of Classical Chemotherapy Drugs
Target Highly proliferative cells => Hair, GI tract, Bone Marrow
General Side Effects
Myelosuppression
- infections (↓WBCs), anaemia (↓RBCs) and bruising (↓platelets) (esp antimetabolites & mitotic inhibitors)*
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Gastro-Intestinal -
Mouth ulcers (mucositis - esp antimetabolites),
nausea & vomiting (esp alkylating agents), diarrhoea*
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Specific Side Effects
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*Haemorrhagic cystitis - Cyclophosphamide (activated in the liver to phosphoramide mustard and acrolein)*
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Neurotoxicity
- Paclitaxel & other mitotic inhibitors
- Cisplatin
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Chemotherapy Terminology
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Induction -
Given to induce remission, commonly used in the context of leukaemia treatment
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Definitive -
Curative e.g. for an early stage tumour that is chemotherapy sensitive - testicular cancer
Palliative -
Not curative, used for symptom management*
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Radiotherapy in Cancer
- Linear accelerator first used in 1950s → much higher energies & better focusing possible
- 2 yo with retinoblastoma → block of lead with pinhole for X-ray focus
- Current linear accelerators → even higher energy + 3D scanning (stereotactic)
- Targets tumours precisely with greatly reduced side effects
- Widely used in many solid tumours, Hodgkins lymphoma, testicular tumours*
Mechanisms
- Damages DNA → apoptosis
- Ionises water → free radicals
Types
- External beam
- Brachytherapy - sealed source
- Systemic radioisotope therapy*
External Beam
- Most use either X-rays (deep) or electron (superficial) beams
- Megavoltage (1-25 MV) versus diagnostic X-rays (20-150 kV)*
*Kill fast growing cells - tumour cells
Also kill fast growing normal cells:
cause serious side effects
limits effective dosing
But eradicate many tumours:
testicular cancers
childhood leukaemias
Efficacy is limited in most tumour types →
solid tumours & advanced disease
Need to develop drugs targeted to cancerspecific
mutations & to identify biomarkers
to select patients with those mutations
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Mulitnucleated
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Here 99.9% effective chemo reduces number of tumour cells from 10^10 to 10^7 - below detectable size (in remission)
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