chemotherapy biologics

Question 1

targeted therapy

Answer 1

Exploits biological weaknesses in tumours
Faulty genes
Faulty signalling systems
Tumour growth
Angiogenesis
Hormonal targets: may antagonise hormones responsible to promoting tumour growth e.g., oestrogens in breast cancer
Molecular testing of cancer cells to determine receptor expression

Question 2

tamoxifen

Answer 2

Tamoxifen is a selective [o]estrogen-receptor modulator (SERM)
It binds to receptors and reduces/modules/modifies their activation by oestrogen.

Reduces growth of oestrogen-driven breast cancer
Used in [O]Estrogen Receptor positive (ER+) breast cancer

As a receptor modulator:
Tamoxifen prevents bone loss via oestrogenic effects

Question 3

aromatase inhibitors

Answer 3

e.g. anastrozole
Prevents peripheral conversion to oestrogens in post-menopausal women
Used in the treatment of breast cancer in post-menopausal women

Question 4

HER2

Answer 4

human epidermal growth factor 2.
Protein that is naturally present in low levels
But over expressed in some cancers e.g., (25% of) breast cancer cases
Leads to a faster growth and spread of the tumours

More likely in older patients
Due to oncogene (ERBB2)
Affects gene transcription and cell cycle

Question 5

trastuzumab

Answer 5

monoclonal antibody (mAb)
Targets human epidermal growth factor receptor-2 (HER2)
Early breast cancer and metastatic breast cancer with HER2 positive tumours

Question 6

epidermal growth factor receptors EGFR

Answer 6

Erlotinib
‘Small molecule’ approach
Certain Lung and pancreatic cancers

Question 7

Tyrosine kinase activity

Answer 7

Philadelphia (Ph) Chromosome is associated with Chronic Myeloid Leukaemia

Ph produces abl-bcl protein which has tyrosine kinase activity
Tyrosine kinase = uncontrolled cell growth

Question 8

tyrosine kinase (TK) inhibitor

Answer 8

Tyrosine kinase leads to uncontrolled cell proliferation

Imatinib inhibits TK activity
Selective inhibitor of TK and is very effective for Chronic Myeloid Leukaemia (CML)
Trials - >90% patients with CML alive after 5 years
Also used in treating Gastro-intestinal stromal tumours

Question 9

proteasome inhibitors

Answer 9

Proteasomes: are molecules which degrade unneeded/damaged proteins (apoptosis).

Cancer cells are more dependent on the proteasomes for clearance of abnormal or mutant proteins than the normal cell.

Inhibitors of proteasomes should prevent malignant cells from proliferation.
Bortezomib is a proteasome inhibitor and is used in multiple myeloma (cancer of bone marrow)

Question 10

anti-VEGF (angiogenesis inhibitors)

Answer 10

Vascular Endothelial Growth Factor (VEGF) are:
secreted to promote angiogenesis.
Angiogenesis: blood vessel growth to support metastasis

Bevacizumab: monoclonal antibody (mAb)
Used in advanced colon cancer and breast cancer

Sunitinib: inhibits VEGF-associated receptor tyrosine kinase
(TK)
Advanced renal carcinoma