Wk 15: Lung cancer

Question 1

Why are x-rays used to diagnose?

Answer 1

• Identifies abnormal mass
• Primary tumour/metastases observed

Question 2

What are the advantages of using a CT scan?

Answer 2

• Traverse through stacked images - not static
• Higher resolution + clarity detecting tumours

Question 3

How is a PET combined CT scanner used to detect smaller tumours?

Answer 3

• Uses IV radioactive tracer (18f-fluouroxyglucose)
• CT run same to outlines tissue/structures

Question 4

How is a biopsy obtained for diagnosis?

Answer 4

• Small incision in skin w/ needle
• Bronchoscope inserted in mouth/nose into lungs

Question 5

Where is squamous cell carcinoma found?

Answer 5

Epithelial cells lining lungs - central portion of lung + airways

Question 6

Where is adenocarcinoma found?

Answer 6

• Bronchial/alveolar epithelium
• Most common in non-smoking women

Question 7

Where is large cell cancers found?

Answer 7

• Large cells of lungs in peripheral tissue
• Large + rapidly growing

Question 8

What is used to diagnose if pathology is not clear?

Answer 8

Cell surface markers used to identify (IHC)

Question 9

What are examples of paraneoplastic syndromes?

Answer 9

• ADH: hyponatraemia (inappropriate ADH secretion)
• ACTH: cushing syndrome
• Parathyroid, prostaglandins + cytokines: hypercalcemia
• Calcitonin: hypocalcaemia
• Gonadotropins: gynecomastia
• Serotonin + bradykinin: carcinoid syndrome

Question 10

What are the top 2 most prominent genetic alterations?

Answer 10

• EGFR mutations
• ALK fusion

Question 11

How does EGFR mutation cause lung cancer?

Answer 11

• Sensitising mutation
• Activated oncogene
• Proliferation
• Dec apoptosis
• Inc angiogenesis

Question 12

What are used to inhibit EGFR?

Answer 12

Tyrosine kinase inhibitors

• Erlotinib
• Gefitinib
• Osimertinib

Antibody: cetuximab

Question 13

What is the mechanism of action of erlotinib?

Answer 13

• Tyrosine kinase inhibitor
• Prevents EGFR phosphorylation
• Inhibits MAPK/AKT
• Inhibits proliferation
• Tumour regression
• Resistance w/in 10-14 months

Question 14

What happens in erlotinib, gefitinib and afatinib resistance?

Answer 14

• T790M mutation in ATP binding pocket
• Survival <2yrs

Question 15

What is given if T790M positive?

Answer 15

• Osimertinib (tagrisso)
• Irreverisble EGFR-TKI
• Diff. selectivity bc doesn’t match standard EGFR structure so only effect cancer cells

Question 16

What produces resistance to osimertinib?

Answer 16

• MET amplification
• EGFR C797S mutation
• HER2 amplification, PIK3CA + RAS mutation

Question 17

What is EML4-ALK gene fusion?

Answer 17

• ALK: cell receptor
• EML: structural protein
• ALK activated in NSCLC by mutation -> hyperphosphorylation + activation
• ALK fuses to EML4 -> ELM4-ALK fusion protein -> drives protein function
• Activates multiple pathways -> proliferation

Question 18

What is the mechanism of action of ELM4-ALK fusion?

Answer 18

• Activates multiple pathways
• Inc proliferation
• Bypass EGFR blockade
• Activates MAPK signalling
• Dec apoptosis

Question 19

What is used to target EML4-ALK receptor tyrosine kinase?

Answer 19

Crizotinib or alectinib

Question 20

What is an example of a RAS inhibitor?

Answer 20

Sotorasib

Question 21

How is immunotherapy used in lung cancer?

Answer 21

• Enhances antitumor immune response
• T Cells attack tumour cells
• T cells contain immune checkpoint receptors to inhibit function - programmed death ligand + receptor PD1
• Tumour cells express PD-L1 to suppress T cells

Question 22

What is used to inhibit PD1 + activate immune system to attack tumours producing antigens?

Answer 22

Pembrolizumab + nivolumab