Lung cancer SD

Question 1

what are the symptoms of lung cancer?

Answer 1

Chest discomfort or pain.
*Trouble breathing.
*Wheezing.
*Blood in sputum
*Hoarseness.
*Trouble swallowing.
*Loss of appetite
*Weight loss for no known reason.
*Feeling very tired.
*A cough that doesn’t go away or gets worse over time.
*Swelling in the face and/or veins in the neck.

Question 2

how do you diagnose lung cancer?

Answer 2

*GP Visit > Blood tests > Imaging > Biopsy > Pathology > Diagnosis >
Treatment

Question 3

what can a x-ray identify?

Answer 3

can identify an abnormal mass

Question 4

what are CT scans?

Answer 4

CT scans are 3 dimensional X-ray images stitched together by Computer
algorithms
*Can traverse THROUGH stacked images – not static like an X-RAY
*Higher resolution and clarity in detecting tumours

Question 5

what is a PET scan?

Answer 5

PET uses an IV radioactive tracer (18f-fluorodeoxyglucose (FDG) which is
detected by the PET scanner
*A combined CT scan runs at the same time to outline the tissues/structures
*Combined PET-CT is very high resolution to detect tumours, plus accurately
locates smaller tumours

Question 6

how do you obtain a biopsy?

Answer 6

*A CT scan or ultrasound is used to locate the mass in the lung.
*A small incision may be made in the skin where the biopsy needle is inserted
*A biopsy is removed with the needle and sent for pathology analysis

Question 7

what is a bronchoscopy?

Answer 7

A bronchoscope is inserted through the nose or mouth into the trachea and lungs.
Biopsies can be taken from the lung for analysis

Question 8

what is SCLC?

Answer 8

–SCLC is highly malignant and spreads very rapidly. Metastases are typically found when a diagnosis is made. Located in central airway
–Tumours are smaller in size compared to NSCLC

Question 9

what are the subtypes of NSCLC?

Answer 9

1. Squamous cell carcinoma, cancer in the epithelial cells lining the
   lungs. Typically found in central portion of the lung and in airways.
2. Adenocarcinoma, a tumour originated from the bronchial/alveolar
   epithelium. Adenocarcinoma is the most common type of lung cancer
   in women who have never smoked.
3. Large cell cancers, originates in larger cells of the lungs, peripherally
   located e.g. large clear cells

Question 10

how do you identify adenocarcinoma?

Answer 10

TTF-1, Napsin A - expressed
in more than 85% of the adenocarcinomas.
Confirms adenocarcinoma

Question 11

how do you identify squamous cell carcinoma?

Answer 11

p63, CK5 / CK6, SOX2 and Desmoglein-3

Question 12

how do you identify small cell lung cancers?

Answer 12

LMWK, CAM5.2, chromogranin, synaptophysin,
CD5/6, CK5 and NKX2-1 / TTF-1

Question 13

what elaborates paraneoplastic syndromes?

Answer 13

hormones/ hormone- like factors

Question 14

what are the dominant oncogenes that are frequently involved in cancer?

Answer 14

–c-MYC
–KRAS(G12C)
–EGFR
–RET
–NTRK

Question 15

what tumour suppressor genes are commonly lost in lung cancer?

Answer 15

–p53
–RB1
–p16
–Multiple Loci on chromosome 3

Question 16

what genes are associated with small cell lung carcinoma?

Answer 16

*C-KIT (40–70%)
*MYCN and MYCL (20–30%)
*p53 (90%)
*3p (100%)
*RB (90%)
*BCL2 (75–90%)

Question 17

what genes areassociated with non-small cell lung carcinoma?

Answer 17

EGFR (25%)
KRAS (10–15%)
p53 (50%)
p16 INK4a (70%)

Question 18

what are the genes associated with non-small cell lung carcinoma?

Answer 18

EGFR (25%)
KRAS (10–15%)
p53 (50%)
p16 INK4a (70%)

Question 19

what are some drug therapies for NSCLC?

Answer 19

chemo
Targeted Therapy
–EGFR signalling
–ALK signalling
–RAS Signalling
–Angiogenesis signalling
*Immunotherapy
–PD-L1 inhibitors

Question 20

what inhibits EGFR?

Answer 20

tyrosine kinase inhibitors

Question 21

what are the main TKIs?

Answer 21

*Erlotinib (Tarceva)
*1st gen and 1st line
*Gefitinib (Iressa)
*1st gen and 1st line
*Osimertinib (Tagrisso)
*3rd gen and when gen 1 fails

Question 22

what is a monoclonal antibody against EGFR?

Answer 22

*Cetuximab (Erbitux)

Question 23

how does erlotinib work?

Answer 23

*Tyrosine Kinase Inhibitor (TKI)
*Prevents EGFR phosphorylation
*Inhibits MAPK / AKT
*Inhibits proliferation
*Tumour regression
*Resistance can occur within 10-14
months

Question 24

what is the mutation that occurs in erlotinib in the ATP binding pocket?

Answer 24

T790M mutation occurs in the ATP
binding Pocket

Question 25

what does the T790 mutation do?

Answer 25

Acquires resistance to Erlotinib,
Gefitinib, Afatinib

Question 26

why does osimertinib work?

Answer 26

*Molecular shape of Osimertinib matches the shape of the mutant T790M protein
structure
*Does not match the standard (WT) EGFR structure
*Osimertinib therefore effects just cancer cells but not ‘normal’ cells

Question 27

what does osimertinib do?

Answer 27

Irreversible EGFR-TKI given to EGFR sensitising and EGFR – T790M mutant patients

Question 28

what benefit does osimertinib have?

Answer 28

*Structural difference gives different selectivity overcoming T790M

Question 29

what does the genetic change in ALK and ELM form?

Answer 29

FUSION protein
*ALK actually fuses to another protein called EML4 to generate
*EML4-ALK fusion protein which then drives the protein function.

Question 30

how does the ALK fusion work?

Answer 30

Activate multiple pathways
*Increase proliferation and
cell cycle
*Bypasses EGFR blockade
*Activates MAPK signalling
*RAS
*RAF
*MEK
*ERK
*cyclins
*proliferation
*Decreases apoptosis

Question 31

what is the purpose of lung cancer immunotherapy?

Answer 31

*Elicits / enhances anti-tumour immune response

Question 32

how does lung cancer immunotherapy work?

Answer 32

T cells are capable of immune attack of Tumour cells
*T cells contain immune checkpoint receptors to inhibit function
*Programmed Death Ligand (PD-L1) and it’s receptor PD1 are part of the immune checkpoint system
*Tumour cells express PD-L1 to suppress T-Cells
*Pembrolizumab (Keytruda®) and Nivolumab (Opdivo®) can inhibit PD1 and
activate the immune system to attack tumours producing antigens