Outlook for Ovarian Cancer
Poor
Typical Symptoms for Ovarian Cancer
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)
What is targeted during targeted cancer approaches
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
Potential biological weaknesses in tumours that may be targeted in therapy
Faulty genes
Faulty signalling systems
Tumour growth
Angiogenesis
Role of oestrogen in breast cancer spread
Oestrogens can stimulate the growth of metastatic breast cancer cells
Hormone-based therapy in breast cancer
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
Tamoxifen
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
Role of Tamoxifen as a Receptor Modulator outside of breast cancer
Prevents bone loss via oestrogenic effects - helps prevent osteoporosis
Mechanism of Tamoxifen
Prevents the stimulation of metastatic cells after the primary tumour is removed
These cells can then get killed off locally
Aromatase
Enzymes that convert androgens (like testosterones) into oestrogen
**Found in post-menopausal women
Aromatase Inhibitors
Anastrozole
Prevents peripheral conversion to oestrogens in post-menopausal women
HER2
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
What proportion of breast cancers are HER2 positive
25%
**DONT MEMORISE JUST BE VAGUELY AWARE
Mechanism of HER2 Receptor breast cancer growth
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
Trastuzumab
Monoclonal Antibody targeting cells that express the HER2 Receptor
Slows down/kills off metastatic breast cancer with HER2 positive tumours
Epidermal Growth Factor (EGF receptor) kinase
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
Philadelphia Chromosome
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
Which cancer has significant Philadelphia chromosome activity
Chronic Myeloid Leukaemia
Tyrosine Kinase Inhibitor
Tyrosine Kinase leads to uncontrolled cell proliferation
Imitinib inhibits TK activity
Selective inhibitor very effective for chronic nyeloid leukaemia
Imatinib
Tyrosine Kinase Inhibitor that is selective for TK and very effective for chronic myeloid leukaemia (CML)
Has really revolutionised the treatment of CML
PARP Inhibitors
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
Vague qualitative efficacy of PARP Inhibitors
Very efficacious
Proteasome inhibitor
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
Angiogenesis
Blood vessel growth to support metastasis
Anti-VEGF
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
