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

  1. Vaccination strategies
  1. Immune checkpoint blockades
  1. Adoptive cell transfer

CAR-T = chimeric antigen receptor t-cell therapy

  1. 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