Biological Therapy

Question 1

What are the 4 concepts of immunotherapy?

Answer 1

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

Question 2

6 types of immunotherapy

Answer 2

Monoclonal antibodies (-mab)

Tyrosine kinase inhibitors (-mib)

Non-specific immunotherapies

Oncolytic virus therapy

T cell therapy

Cancer vaccines

Question 3

How do monoclonal antibodies work?

Answer 3

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

Question 4

What are immune checkpoints + name the 2 important ones?

Answer 4

PD-1/PD-L1 and CTLA-4 pathways

Critical to immune system’s ability to control cancer growth

Question 5

How do tyrosine kinase inhibitors work?

Answer 5

Tyrosine kinase = enzymes that activate proteins by signal transduction cascades

Activated by phosphorylation

TKIs inhibit this

Question 6

SE of monoclonal antibody treatment + management

Answer 6

Fatigue, diarrhoea, colitis, skin rash, transaminitis, glomerulonephritis

Pneumonitis Hypo/hyperthyroidism

Immune side effects mimic infection

Managed with steroids

Question 7

What are non-specific immunotherapies, what are the SE of each?

Answer 7

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

Question 8

How does trastuzamab work + how is it administered?

Answer 8

IV infusion

Monoclonal antibody to protein called human epidermal growth factor receptor 2 (HER2)

Work against HER2 positive cancers

Trastuzumab blocks HER2 receptor

Question 9

Indications for trastuzumab

Answer 9

HER2 positive breast cancer

Question 10

SE of trastuzumab

Answer 10

Acne, alopecia, angioedema, bone pain, bone marrow suppression, cardiotoxic, dry eyes + skin

Question 11

Interactions of trastuzumab

Answer 11

Alteplase + anticoagulants = increased risk of bleeding

Glucose = risk of bleeding

Question 12

Action of tamoxifen

Answer 12

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

Question 13

Serious + common SE of tamoxifen

Answer 13

Serious = increased risk of uterine cancer, stroke, vision problems + pulmonary embolism

Common = irregular periods, weight loss, hot flushes, mood changes, vaginal discharge, endometrial changes

Question 14

Action of Letrozole/ Anastrazole

Answer 14

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

Question 15

Indications for Letrozole/ Anastrazole

Answer 15

Adjuvant treatment of oestrogen receptor positive early breast cancer in postmenopausal women (can be used after tamoxifen)

Question 16

Contraindications for Letrozole/ Anastrazole

Answer 16

Pre-menopausal women

Susceptibility to osteoporosis

Question 17

SE of Letrozole/ Anastrazole

Answer 17

Anorexia, cutaneous vasculitis, drowsiness, hair thinning, vasomotor, Steven johnsons

Question 18

What SE do you get from drugs targeting EGFR pathway?

Answer 18

Acneiform rash

Diarrhoea

Question 19

Which cancers are most hormone sensitive?

Answer 19

Prostate, breast, endometrium, lymphocytic malignancies (lymphoma, myeloma, leukaemia)

Question 20

What is the mechanism between steroid hormones + tumours?

Answer 20

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)

Question 21

What is medical castration in women?

Answer 21

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

Question 22

How do aromatase inhibitors work?

Answer 22

Inhibit aromatisation of adrostenedione to oestrone in fat + liver of postmenopausal women

Reduces oestrogen synthesis

Question 23

Examples of aromatase inhibitors

Answer 23

Anastrozole, exemestane, letrozole

Question 24

Types of anti-androgen, their effect in the body and uses in cancer

Answer 24

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

Question 25

How are glucocorticoids used in cancer therapy?

Answer 25

Induce apoptosis in malignant lymphoid cells - treat leukaemias, lymphomas, myelomas + Hogdkins disease

Question 26

When is hormone supplementation used + give examples?

Answer 26

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

Question 27

When are progestogens used?

Answer 27

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

Question 28

SE of immunotherapy

Answer 28

Fatigue

Gut: diarrhoea, colitis

Skin: rash, itch

Liver: transaminitis

Renal: glomerulonephritis

Lung: pneumonitis

Endocrine: low/high thyroid, hypophysitis (pituitary)