therapeutic options in cancer e.g. chemotherapy Flashcards
what are the therapeutic options for cancer?
- Prevention
Environment / Behaviour change
Diet
Screening
Genetics
Medication / Vaccination - Treatment
Surgery
Radiotherapy
Systemic therapy
Immunotherapy
what are 5 rs of radiotherapy?
R’s of radiobiology:
[1] radiosensitivity
[2] repair
[3] re-population
[4] re-oxygenation
[5] reassortment
what are local/ regional treatments?
- surgery
- radiotherapy
- ablation (freezing, radio-frequency, etc)
- isolated limb perfusion
what are systemic treatments?
- hormonal therapy
- chemotherapy
- biological therapy
- immunotherapy
- CAR T-cell therapy
- whole body irradiation (for BMT)
why are haemoglobin levels kept high when treating cancer?
Cancer cells are more sensitive to radiation if there is oxygen around them.
→ O2 reacts with radiation and causes more damage to tumour cells.
describe the radiation sensitivity of cells in different cell phases :
Cells in G2 and Mitosis (G2M) - most sensitive to radiation
Cells in S phase (doubling DNA) - least sensitive to radiation
describe what systemic treatment is and its effects:
- beneficial for widespread disease
- can result in widespread toxicity (systemic & non-specific)
- a mixture of chemotherapy & targeted agents
what are some target agents?
- potential to be very specific
- hormone therapy: tamoxifen & ER+ve breast cancer
- targets tumour mutation: EGFR mutations & TKI agents
EGFR - epidermal growth factor receptor
TKI - tyrosine kinase inhibitor
state what these terms are:
Curative → completely cure the cancer
Adjuvant
- given in addition to primary treatment to maximize its effectiveness
- reduce risk of cancer coming back after surgery
Neoadjuvant → pre-surgery therapy
e.g. radiotherapy before surgery = more likely to get cancer out
Palliative → reduction of suffering and pain
what do the target agents imatinib and EGFR inhibitors do?
imatinib:
→ tyrosine kinase inhibitor (TKI)
very useful in CML & GISTS
- EGFR inhibitors:
→ in lung cancer needs to have a specific EGFR mutation to work effectively.
the relationship between chemotherapy and therapeutic index:
Chemotherapy crosses the line into toxicity
5% of patients may have a recurrence of toxicity
- due to the very similar anti-tumour effect range and normal tissue toxicity range.
what are the characteristics of immune therapy?
Non-specific
innate:
- macrophages / NK cells
programmed cell death pathway (PD-1):
- uses the immune system to attack ‘foreign’ cancer cells
Specific
monoclonal antibodies:
- rituximab & B cell NHL: +/- radioactivity
- trastuzumab & response in HER2 +ve breast & gastric cancer
chimeric antigen receptor (CAR) T-cells:
- artificial T-cell receptors, using retroviral vectors to give a specific cell-killing function directed against cancer cells
what is HER2-positive breast cancer?
a breast cancer that tests positive for a protein called human epidermal growth factor receptor 2 (HER2).
This protein promotes the growth of cancer cells.
describe neoadjuvant therapy:
locally advanced rectal cancer:
response & survival to pre-operative chemo-radiotherapy
- linked with ‘natural killer’ cell activity in specimens
→ Increased NK cells linked with increased response
→ Increased survival, irrespective of response grade, linked with increased NK cell activity
what are the mechanisms of checkpoint blockade?
Tumour cells fool the immune system
- PD-L1 binds to PD-1
-causes T cell deactivation
PD-1 & PDL-1 antagonists - help prevent T cell deactivation
clinical use:
- melanomas
- lung cancer
Interesting clinical trials
* genitourinary cancers
* UGI cancers
* MSI-H CRC
Success depends on:
a) mutation burden of cancer
→ somatic mutation frequency
b) immunogenicity of neoantigens
