Targeted Cancer Therapy

Question 1

Outlook for Ovarian Cancer

Answer 1

Poor

Question 2

Typical Symptoms for Ovarian Cancer

Answer 2

Non-specific abdominal pain that may be misinterpreted as IBS
Pain during intercourse/vaginal bleeding
Increased urination
Other typical cancer symptoms (weight loss, fatigue, etc)

Question 3

What is targeted during targeted cancer approaches

Answer 3

Biological Weaknesses in tumours

Hormones responsible to promoting tumour growth (e.g. oestrogen in breast cancer)

Molecular testing of cancer cells to determine receptor expression

Question 4

Potential biological weaknesses in tumours that may be targeted in therapy

Answer 4

Faulty genes
Faulty signalling systems
Tumour growth
Angiogenesis

Question 5

Role of oestrogen in breast cancer spread

Answer 5

Oestrogens can stimulate the growth of metastatic breast cancer cells

Question 6

Hormone-based therapy in breast cancer

Answer 6

Primary tumour and local nodal spread are targeted via surgery but distant metastasis cannot be targeted via surgery

Hormonal therapy targets the hormones which help mediate and support metastasis to prevent/reduce the severity

Question 7

Tamoxifen

Answer 7

Blocks oestrogen as a selective oestrogen-receptor modulator (SERM)

Prevents breast cancer and reduces growth of oestrogen-driven breast cancer

Used in oestrogen receptor positive breast cancer

*usually used post surgery

Question 8

Role of Tamoxifen as a Receptor Modulator outside of breast cancer

Answer 8

Prevents bone loss via oestrogenic effects - helps prevent osteoporosis

Question 9

Mechanism of Tamoxifen

Answer 9

Prevents the stimulation of metastatic cells after the primary tumour is removed

These cells can then get killed off locally

Question 10

Aromatase

Answer 10

Enzymes that convert androgens (like testosterones) into oestrogen

**Found in post-menopausal women

Question 11

Aromatase Inhibitors

Answer 11

Anastrozole

Prevents peripheral conversion to oestrogens in post-menopausal women

Question 12

HER2

Answer 12

Human Epidermal Growth Factor Receptor 2

Naturally present at low levels but over expressed in some cancers due to oncogenes (more commonly over-expressed in older patients)

Affects gene transcription & cell cycle causing proliferation and over-prescription in positive tumours

Question 13

What proportion of breast cancers are HER2 positive

Answer 13

25%

**DONT MEMORISE JUST BE VAGUELY AWARE

Question 14

Mechanism of HER2 Receptor breast cancer growth

Answer 14

Tyrosine kinase is stimulated by HER2 Receptors (phorphorelates tyrosine)

This leads to multiple signalling cascades that lead to dysregulation of the cell cycle and affecting DNA transcription, releasing VEGF, COX2 & Cyclins

These work to increase tumour growth

Question 15

Trastuzumab

Answer 15

Monoclonal Antibody targeting cells that express the HER2 Receptor

Slows down/kills off metastatic breast cancer with HER2 positive tumours

Question 16

Epidermal Growth Factor (EGF receptor) kinase

Answer 16

Erlotinib

‘Small molecule’ approach

Used in Certain lung and pancreatic cancers (that are EGF positive I think)

Tyrosine Kinase Inhibitor

• *EGF Stimulates tyrosine kinase
• *Don’t confuse this with eGFR

Question 17

Philadelphia Chromosome

Answer 17

Translocation of the abl gene from chromosome 9 onto chromosome 22

They join together to form an abl-bcr gene on a Philadelphia chromosome which has tyrosine kinase activity

**DONT NEED TO LEARN CHROMOSOME NUMBERS

Question 18

Which cancer has significant Philadelphia chromosome activity

Answer 18

Chronic Myeloid Leukaemia

Question 19

Tyrosine Kinase Inhibitor

Answer 19

Tyrosine Kinase leads to uncontrolled cell proliferation

Imitinib inhibits TK activity

Selective inhibitor very effective for chronic nyeloid leukaemia

Question 20

Imatinib

Answer 20

Tyrosine Kinase Inhibitor that is selective for TK and very effective for chronic myeloid leukaemia (CML)

Has really revolutionised the treatment of CML

Question 21

PARP Inhibitors

Answer 21

Olaparib

PARP - Poly (ADP-ribose) Polymerase; repairs DNA

BRCA genes (tumour suppressor) important in DNA repair at double strand breaks; PARP enzyme repairs single strand breaks

In BRCA Mutations, Olaparib leads to inability of cancer to repair itself at single strand breaks, causing cell death for cancer cells

Approved for some forms of ovarian cancer

Question 22

Vague qualitative efficacy of PARP Inhibitors

Answer 22

Very efficacious

Question 23

Proteasome inhibitor

Answer 23

Proteosomes: Cellular structures which degrade proteins

Some proteins kill cancer cells: pro-apoptotic factors

Inhibition of intracellular proteasomes alters the regulation of intracellular proteins and prevents the breakdown of these pro-apoptotic factor

Question 24

Angiogenesis

Answer 24

Blood vessel growth to support metastasis

Question 25

Anti-VEGF

Answer 25

Vascular Endothelial Growth Factor

VEGF secreted to promote angiogenesis

Bevacizumab - mAB for advanced colonic & breast cancer

Sunitinib - Inhibits VEGF-associated receptor tyrosine kinase
- Advanced renal carcinoma