Prostate Cancer

Question 1

Primary symptom of prostate cancer

Answer 1

Problems with urination

Question 2

Where do prostate adenocarcinomas arise?

Answer 2

Luminal epithelial cells

Basal epithelial layer is absent

Question 3

Component in fluid which is useful to detect

Answer 3

Prostate specific antigen (PSA)

Question 4

Hormone driven development of prostate

Answer 4

Sertoli cells= secrete anti mullerian hormone, mullerian ducts regression
Leydig cells = secrete T, formations of vas deferens and seminal vesicles
DHT- drives growth of prostate
At puberty, prostate grows significantly

Question 5

GnRH and T secretion

Answer 5

GnRH➡️anterior pituitary ➡️LH➡️ acts on testis to secrete T➡️ targets prostate

Question 6

Structure of androgen receptors

Answer 6

DNA binding domain (DBD) in the middle
Ligand binding domain (LBD)-binds to T and DHT
AF1 domain binds cofactors

Question 7

Androgen cell receptor signalling

Answer 7

AR sits in the cytoplasm when no ligand around
DHT binds to AR ➡️ dimerisation of receptor
Moves into nucleus
Binds to androgen response element
Cofactor proteins bind to AR and activate or repress transcription

Question 8

What do therapies target

Answer 8

Androgens.

They caus growth of the prostate and cell division and growth of tumour

Question 9

Genes implicated in prostate cancer

Answer 9

PTEN - TSG lost in prostate cancer.

BRCA2 - familial prostate cancer

Question 10

What does high PSA suggest?

Answer 10

Secretion of PSA into blood suggests disruption of basal lamina - tumour disruption of tissue?

Question 11

What is PSA

Answer 11

Serine protease
Clears seminal vesicles
Regulated by androgens

Question 12

Where does prostate cancer metastasise to

Answer 12

Bone

Question 13

Treatments for different grades?

Answer 13

Low grade: surveillance
Confined to prostate: surgery
Confined or local spread: RT
Metastatic: hormone therapy

Question 14

Types of therapies

Answer 14

Anti GnRH - busrelin
Anti androgen - enzalutamide, inhibits growth of androgen dependent prostate cancer
Anti synthesis - abiraterone

Question 15

Pituitary down regulator therapy

Answer 15

GnRH analog
Initial rise in LH and T
After a while - inhibition of LH ant T
Analogues dont give receptors chance to get degraded - become internalised. Pituitary becomes resistant to stimulation

Question 16

Anti androgen therapy

Answer 16

Bind to AR in LBD and inhibit it
Competition with ligand for binding
Stop nuclear localisation of AR
Could prevent dimerisation of DNA and DNA binding
Promote corepressors

Question 17

Anti-synthesis therapy

Answer 17

Get rid of androgens from all sources
Inhibit androgen synthesis
Used with chemical castration

Question 18

Side effects of inhibiting androgens

Answer 18

Osteoporosis
Loss of muscle and libido
Hot flushes

Question 19

Prostate cancer therapy resistance

Answer 19

Loss of ligand specificity - mutation of AR, becomes activated by other hormone ligands
Alterations in cofactor levels - corepressors expelled from nucleus they cant bind to DNA, treatment not effective
AR over expression

Question 20

Future therapies

Answer 20

New antagonists with tissue specific activity - no SEs
Peptide inhibitors of receptor/coactivator interactions
Targeting other signalling pathways that crosstalk with AR signalling