Endocrine cancer Flashcards
What is endocrine cancer?
Cancers that occur in an endocrine tissue
How can hormones act on cancer?
Causation
Progression
Resistance
Treatment
What are the three types of endocrine cancer?
Tumours of endocrine organs
Endocrine-related cancers
Neuroendocrine cancers
Describe oestrogens as a cancer initiator?
Oestrogens induce DNA mutations in cell lines in vivo and rodents in vitro
Oestrogen DNA adducts form from covalent bonding of oestrogen metabolites to DNA
What is AID?
Activation-induced deaminase An enzyme that creates mutations in DNA Converts CG to TA Necessary for B cell function/diversity Oestrogens increase AID activity 20x
What is APOBEC3?
Enzymatic source of mutations in breast cancer
The AID enzyme APOBEC3 was unregulated in 20 out of 52 studied breast tumours
This has poor outcome correlation for ER+ tumours
HPV infection also linked to APOBEC3 induction and breast cancer carcinogenesis
Describe oestrogens as promoters
Potent stimulators of proliferation
Enhance tumour growth
Increased chance of errors in DNA replication
Accumulation of genetic alterations
60-70% of breast tumours require oestrogen to grow
Describe the prevalence of cancers of the endocrine organs
In the US, ~27,650 diagnoses each year
25,000 thyroid
298,000 thyroid cancer diagnoses globally
Highest incidence is Lithuania, 24 in 100,000
What are the risk factors for thyroid cancer?
Gender Age Exposure to radiation History of nodules Family history Iodine deficiency Serum TSH levels
What is the common mutation of follicular thyroid cancer?
RAS
What is the common mutation of papillary thyroid cancer?
BRAF
Describe BRAF mutations
4 distinct sub-groups
What are the two types of aggressive thyroid cancer?
Poorly differentiated thyroid cancer
Anaplastic thyroid cancer
What are causes of thyroid cancer other than genetic mutations?
Epigenetic changes
Changes in the microenvironment
Disregulation of miRNAs
How is thyroid cancer treated?
Surgical resection followed by radioiodine treatment to ablate the thyroid
What are the side effects of radioiodine ablation?
Swelling of salivary glands
Loss of taste
Secondary cancers
What is the survival rate of thyroid cancer?
10 year survival rate of metastatic cancer is 60% if the cell takes up radioiodine
10% if this fails
What is the cause of radioiodine resistant thyroid cancer?
Radioiodine is taken up by NIS
BrafV600E mutation driving the cancer represses NIS expression
BrafV600E activates MEK/ERK signalling to promote proliferation
How do you treat metastatic radioiodine resistant thyroid cancer?
New kinase inhibitor treatments
Common pathways so many side effects
What is Vemurafinib?
Specific to BrafV600E mutation
What is Sorafenib?
Targets VEGFR
Increases progression free survival by 10 to 20 months
Side effects include hypertension, dermatological, fatigue, diarrhoea
Risk of bleeding and liver toxicity may be fatal
How do you restore radioiodine uptake?
Selumetinib - MEK/ERK pathway
Dabrafenib - BRAF
