Targeted agents

Question 1

Give 3 examples of Monoclonal antibodies and what they are used for?

Answer 1

• Transtuzumab (herceptin) against HER2 used in breast cancer patients with HER2+ disease
• Ipiluzumab anti-CTLA4 (cytotoxic lymphocyte 4), which blocks regulatory immune function releasing effective anti-tumour immunity. Licensed for treatment of metastatic melanoma
• Rituximab (used for rheumatoid arthritis)

Question 2

Give 4 examples of tyrosine kinase inhibitors and when they would be used ?

Answer 2

• imatinib: used in CML with Philadelphia chromosome
• Sunitinib (Sutent) anti-VEGFR, multi-targeted oral tyrosine kinase inhibitor which can block cell growth factors and angiogenesis and is used for palliative treatment of patients with renal cell cancer, pancreatic neuroendocrine tumours and gastro-intestinal stromal tumours
• Erlotinib (Tarceva) anti-EGFR, used for patients with NSCLC
• Vemurafenib is effective palliative therapy for patients with V600E BRAF mutation metastatic melanoma

Question 3

what do mTor inhibitors do?

Answer 3

part of intracellular signalling pathway important in apoptosis and hence has a role in cell longevity

Question 4

when can hormone therapy be given? (what stages of cancer)

Answer 4

• all stages
• primary medical therapy
• adjuvant therapy
• palliative therapy

Question 5

How may you “remove the source of a growth promoting hormone”?

Answer 5

• long acting LHRH analogues (goserelin, leuprorelin)

Question 6

how do LHRH analogues work?

Answer 6

block gonadal hormone output (LH and FSH)

Question 7

Why are these techniques unsuitable for post- menopausal women? What is the alternative therapy?

Answer 7

• oestrogen release is mainly extra-gonadal in fat and adrenal glands
• aromatase inhibitors (anastrozole, exemestane, letrozole)

Question 8

Give examples of hormone inhibitors?

Answer 8

• tamoxifen (anti-oestrogen) blocks binding of hormones to receptors

Question 9

What are the two main types of anti-androgens?

Answer 9

• steroid anti-androgens (cyproterone acetate)

- non- steroidal (bicalutamide)

Question 10

How do steroid anti-androgens work?

Answer 10

• inhibit androgen receptor in tumour cells

- in the hypothalamus they substitute for testosterone so decreased LHRH release

Question 11

How do non- steroidal anti androgens work?

Answer 11

• inhibit testosterone in both tumour cells and hypothalamus so feedback inhibition lost and serum testosterone levels rise

Question 12

what is maximum androgen blockade? and when is it used?

Answer 12

• describes the combination of Non-Steroid anti androgen with LHRH analogue
• used in prostate cancer

Question 13

When might you want to increase glucocorticoid hormones?

what cancers tend to benefit from this?

Answer 13

• glucocorticoids in high concentrations induce apoptosis in some malignant lymphoid cells
• helps to treat lymphoid leukaemias, lymphoma, myeloma and hodgkins disease

Question 14

when else would you use hormone supplementation?

Answer 14

• oestrogens given in prostate cancer to downregulate hypothalamic LHRH
• high-dose oestrogens in breast cancer due to tachyphylaxis (high dose decreases sensitivity)

Question 15

when are progestogens given? Give an example of one

Answer 15

• (synthetic progesterone)
• breast, endometrium etc
• megestrol acetate, medroxyprogesterone acetate)

Question 16

how do progestogens work?

Answer 16

• direct inhibition of tumour growth (progesterone receptor agonist)
• negative feedback of pituitary/ gonadal axis