What are the 4 concepts of immunotherapy?
Boosts body's natural defences to fight cancer
Stops/ slows growth of cancer cells
Stops cancer spreading
Helps immune system work better at destroying cancer cells
6 types of immunotherapy
Monoclonal antibodies (-mab)
Tyrosine kinase inhibitors (-mib)
Oncolytic virus therapy
T cell therapy
How do monoclonal antibodies work?
Targeted therapy to block abnormal protein in cancer cell (biological therapy)
Attach to specific proteins on cancer cells.
Flags cells so immune system can destroy them
What are immune checkpoints + name the 2 important ones?
PD-1/PD-L1 and CTLA-4 pathways
Critical to immune system's ability to control cancer growth
How do tyrosine kinase inhibitors work?
Tyrosine kinase = enzymes that activate proteins by signal transduction cascades
Activated by phosphorylation
TKIs inhibit this
SE of monoclonal antibody treatment + management
Fatigue, diarrhoea, colitis, skin rash, transaminitis, glomerulonephritis
Immune side effects mimic infection
Managed with steroids
What are non-specific immunotherapies, what are the SE of each?
Interferons + interleukins
Interferons = slow growth of cancer cells.
SE: flu like S+S, increased risk of infection, rashes + thinning hair
Interleukins = treats kidney + skin cancer.
SE: weight gain, low BP, flu-like S+S
How does trastuzamab work + how is it administered?
Monoclonal antibody to protein called human epidermal growth factor receptor 2 (HER2)
Work against HER2 positive cancers
Trastuzumab blocks HER2 receptor
Indications for trastuzumab
HER2 positive breast cancer
SE of trastuzumab
Acne, alopecia, angioedema, bone pain, bone marrow suppression, cardiotoxic, dry eyes + skin
Interactions of trastuzumab
Alteplase + anticoagulants = increased risk of bleeding
Glucose = risk of bleeding
Action of tamoxifen
Reduces oestrogen activity - used in ER or PR+ disease
Used for 5 years post-op
Selective oestrogen receptor modulator
Antagonist in breast and agonist in bone + uterus
Serious + common SE of tamoxifen
Serious = increased risk of uterine cancer, stroke, vision problems + pulmonary embolism
Common = irregular periods, weight loss, hot flushes, mood changes, vaginal discharge, endometrial changes
Action of Letrozole/ Anastrazole
Nonsteroidal aromatase inhibitor for treatment of hormonally responsive breast cancer post surgery
Letrozole only effect in post-menopause (when oestrogen is predominantly in peripheral tissue)
Inhibits conversion of androgens to oestrogens
Indications for Letrozole/ Anastrazole
Adjuvant treatment of oestrogen receptor positive early breast cancer in postmenopausal women (can be used after tamoxifen)
Contraindications for Letrozole/ Anastrazole
Susceptibility to osteoporosis
SE of Letrozole/ Anastrazole
Anorexia, cutaneous vasculitis, drowsiness, hair thinning, vasomotor, Steven johnsons
What SE do you get from drugs targeting EGFR pathway?
Which cancers are most hormone sensitive?
Prostate, breast, endometrium, lymphocytic malignancies (lymphoma, myeloma, leukaemia)
What is the mechanism between steroid hormones + tumours?
Steroids interact with cytoplasmic protein receptors to form functional DNA transcription factors
Altering this interaction = hormone therapy
Also, presence of cytoplasmic steroid receptors on tumour cells predict hormone sensitivity (eg ER+ in breast ca)
What is medical castration in women?
Using long acting LHRH analogues (goserelin, leuprorelin) which, by receptor down regulation in pituitary, block LH + FSH production + block gonadal hormone output
Only suitable in pre-menopausal women
How do aromatase inhibitors work?
Inhibit aromatisation of adrostenedione to oestrone in fat + liver of postmenopausal women
Reduces oestrogen synthesis
Examples of aromatase inhibitors
Anastrozole, exemestane, letrozole
Types of anti-androgen, their effect in the body and uses in cancer
Steroidal (cyproterone acetate) = inhibits androgen receptor + substitutes for testosterone in hypothalamus, stimulating negative feedback inhibition to reduce LHRH release
Non steroidal (bicalutamide) = inhibits testosterone in tumour cells + hypothalamus, losing feedback + causing testosterone to rise.
Combine with LHRH analogue to prevent this effect = used in prostate cancer
How are glucocorticoids used in cancer therapy?
Induce apoptosis in malignant lymphoid cells - treat leukaemias, lymphomas, myelomas + Hogdkins disease
When is hormone supplementation used + give examples?
In sex hormone sensitive cancers:
Oestrogen given to down regulate hypothalamic LHRH in prostate cancer
Tachyphylaxis of receptors - use high dose oestrogens in breast cancer
When are progestogens used?
Given orally in high doses for progesterone sensitive cancers (breast + endometrium)
Inhibit tumour growth (act as agonist of progesterone receptor)
Also stimulate appetite - useful in palliation
SE of immunotherapy
Gut: diarrhoea, colitis
Skin: rash, itch
Endocrine: low/high thyroid, hypophysitis (pituitary)