Advances in Cancer Chemo
Chemoprevention
Block DNA damage or arrest/reverse damage in premalignant cells
supress+prevent carcinogenic progression
NSAIDs
SERMS
Increases TGFb production (inhibits tumour growth) + decreases IGF-1 production (stimulates)
Raloxifene: Post-menopausal at risk or have osteoporosis
Tamoxifen MoA: competitively inhibits estradiol binding of ER -> decreased DNA synthesis + cellular response to E.
estrogen antagonist in uterine and breast tissue, estrogen agonist in lipid metabolism (decreases cholesterol), increases bone resportion. turnover, density
Reduce risk of invasive ER+ breast cancer by 50% in high risk women (44% over 4.2 years)
Aspirin
Decrease many cancer risks in average risk people (esp. colon cancer)
Inhibit NF-kB pathway and downstream COX1 and 2 (promote apoptosis, inhibit proliferation)
Dietary
Cancer blocking agents: inhibit metabolic activation of procarcinogens or subsequent DNA interaction
Stimulate detox of carcinogens
Sulforaphane (broccoli, kale, brussel sprouts, etc)
Cancer supressing agents prevent promotion and progression
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HPV
Vaccine prevents against 7/10 cervical cancers
20-30y later, viral DNA incorporated in tumour genome
80% women contract HPV -> main cause of cervical cancer
Immunotherapy
- Vaccination strategies
- Immune checkpoint blockades
- Adoptive cell transfer
CAR-T = chimeric antigen receptor t-cell therapy
- Nonspecific immune stimulation
CTLA-4 inhibitor
PD-1:PD-L1 inhibitor: block interaction with monoclonal antibodies nivolumab - extremely promising, though only 15% respond
Combining immuno + other therapies: possibly only works sometimes due to low T cell amounts at tumour edge (no inflammation) -> if we could raise T cell response first & recruit
the cells to the edges of the tumour, then patients
might respond better to ckpoint inhibitors