Endocrine cancer

Question 1

What is endocrine cancer?

Answer 1

Cancers that occur in an endocrine tissue

Question 2

How can hormones act on cancer?

Answer 2

Causation
Progression
Resistance
Treatment

Question 3

What are the three types of endocrine cancer?

Answer 3

Tumours of endocrine organs
Endocrine-related cancers
Neuroendocrine cancers

Question 4

Describe oestrogens as a cancer initiator?

Answer 4

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

Question 5

What is AID?

Answer 5

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

Question 6

What is APOBEC3?

Answer 6

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

Question 7

Describe oestrogens as promoters

Answer 7

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

Question 8

Describe the prevalence of cancers of the endocrine organs

Answer 8

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

Question 9

What are the risk factors for thyroid cancer?

Answer 9

Gender
Age
Exposure to radiation
History of nodules
Family history
Iodine deficiency
Serum TSH levels

Question 10

What is the common mutation of follicular thyroid cancer?

Answer 10

RAS

Question 11

What is the common mutation of papillary thyroid cancer?

Answer 11

BRAF

Question 12

Describe BRAF mutations

Answer 12

4 distinct sub-groups

Question 13

What are the two types of aggressive thyroid cancer?

Answer 13

Poorly differentiated thyroid cancer

Anaplastic thyroid cancer

Question 14

What are causes of thyroid cancer other than genetic mutations?

Answer 14

Epigenetic changes
Changes in the microenvironment
Disregulation of miRNAs

Question 15

How is thyroid cancer treated?

Answer 15

Surgical resection followed by radioiodine treatment to ablate the thyroid

Question 16

What are the side effects of radioiodine ablation?

Answer 16

Swelling of salivary glands
Loss of taste
Secondary cancers

Question 17

What is the survival rate of thyroid cancer?

Answer 17

10 year survival rate of metastatic cancer is 60% if the cell takes up radioiodine
10% if this fails

Question 18

What is the cause of radioiodine resistant thyroid cancer?

Answer 18

Radioiodine is taken up by NIS
BrafV600E mutation driving the cancer represses NIS expression
BrafV600E activates MEK/ERK signalling to promote proliferation

Question 19

How do you treat metastatic radioiodine resistant thyroid cancer?

Answer 19

New kinase inhibitor treatments

Common pathways so many side effects

Question 20

What is Vemurafinib?

Answer 20

Specific to BrafV600E mutation

Question 21

What is Sorafenib?

Answer 21

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

Question 22

How do you restore radioiodine uptake?

Answer 22

Selumetinib - MEK/ERK pathway

Dabrafenib - BRAF