A multi-disciplinary understanding of cancer: from tumour biology to clinical care (1)

Question 1

1st step when a breast lump is detected

Answer 1

Screening
mammographic screening

Question 2

Pathology of breast cancer
What type of testing is used and what does it show?

Answer 2

Immunochemistry
- Can identify specific proteins in and on cells
- Identifies the state of cells
-Identifies cell type
-Identifies potential treatment

Question 3

Breast cancer treatment and what does it target

Answer 3

trastuzumab targets Her2 receptor on the surface of epithelial cells that turns on
intracellular signaling pathways (including the PI3K and MAPK pathways)

Question 4

What does the drug do specifically (3)

Answer 4

• Causing Her2 receptor
  lysosomal degradation
• Blocking Her2 PI3K/AKT
  intracellular signaling
• Encouraging immune
  attack

Question 5

Anaplasia vs Dysplasia

Answer 5

Anaplasia = Reduced differentiation

Dysplasia = Abnormal differentiation / Abnormal cell growth

Both Anaplasia and Dysplasia represent failure of normal
signaling pathways in cells due to genetic or epi-genetic changes, you can think of this as a loss of cellular ‘social responsibility’

Question 6

Microscopic appearances of Dysplasia

Answer 6

• Pleomorphism (variation in size and shape between cells)
• Hyperchromatic nuclei and increase in the nucleus/cytoplasm ratio.
• Loss of tissue architecture

Question 7

Oncogene vs protogene

Answer 7

Protogene is normal but when turns cancerous becomes oncogene

Question 8

How does cancer alter the balance of TUMOUR
SUPRESSOR GENES and PROTO-ONCOGENES

Answer 8

Changes to TUMOUR
SUPRESSOR GENES means inactivate proteins (not enough BRAKE)

Changes to PROTO-ONCOGENES
Overactive proteins
‘Too Much Throttle’

Therefore there is a lack of regulation

Question 9

How does cancer relate to the immune system

Answer 9

Tumor cells will prevent activation of T cells by binding to receptots on T cells.
T cells have
CTLA4
PD1

and cancer cells have CD80 and PDL1

CTLA4: CD80
PD1: PDL1

This causses inactivation of t cells preventing immune cell activation

Question 10

What drugs prevent tumor cells suppressing T cells and what receptors specifically

Answer 10

CTLA4: CD80 (ipilimumab)
PD1: PDL1 (nivolumab, pembrolizumab)

Question 11

Some hallmarks of cancer

Answer 11

Evading growth suppressors
Inducing angiogenesis
Tumor promoting inflammation
avoiding immune destruction
resisting cell death