lung cancer SD

Question 1

RF for lung cancer

Answer 1

cigarette smoking

passive smoking

occupational
- asbestos
- ionising radiation
- occupational RF
- air pollution

genetic predisposition

previous malignancies

genetic RF - old age, obesity, poor diet, physical inactivity, alcohol

Question 2

Sx

Answer 2

chest discomfort/pain
trouble breathing
wheezing
blood in sputum
hoarseness
trouble swallowing
loss of appetite
weight loss for no reason
very tired
cough thatdoesn’t go away/worse over time
swelling in face/veins in neck

Question 3

scans that can be used

Answer 3

x-ray

CT scan

PET-CT scan (positron emission tomography)

Question 4

What scan is used to locate mass in a lung?

Answer 4

CT

PET-CT

Question 5

bronchoscopy

Answer 5

• bronchoscope inserted through nose/mouth into trachea and lungs
• biopsy can be taken from lung for analysis

Question 6

classifications of lung cancer

Answer 6

SCLC

NSCLC

Question 7

small cell lung cancer

Answer 7

• mostly caused by smoking
• highly maligant
• spreads rapidly
• metastases when diagnosis made
• located in central airway
• tumours smaller in size compared to NSCLC

Question 8

non-small cell lung cancer types

Answer 8

most common types:

1. squamous cell carcinoma
2. adenocarcinoma
3. large cell cancers

Question 9

squamous cell carcinoma

Answer 9

cancer in epithelial cells lining the lungs

typically in central portion of the lung and in airways

Question 10

adenocarcinoma

Answer 10

• tumour originated from bronchial/alveolar epithelium
• most common type of LC in women who ever smoked

Question 11

large cell cancers

Answer 11

• originate in larger cells of the lungs
• peripherally located
• eg. large clear cells

Question 12

staging of lung cancer tumour

Answer 12

stage 1: <3cm, not spread, small

stage 2: 3-5cm, in lymph nodes in lungs,

stage 3: 5-7cm, in lymph nodes away from primary tumour, other organs/tissues, invading into chest wall/breast bone

stage 4: >7cm, spread to other lung, in many lymph nodes, metastasised to ANOTHER ORGAN

Question 13

What are micro metastases?

Answer 13

metastses in another organ that can’t be seen on x-ray or CT scan

don’t have eough biomarkers yet

Question 14

What can be used to diagnose LC if pathology not clear?

Answer 14

IHC - immuno histo chemistry

Question 15

What are paraneoplastic syndromes assocated with LC?

Answer 15

secondary effetcs of the cancer

producing chemicals and hormones

Question 16

paraneoplastic syndromes with LC

Answer 16

• ADH: inducing HYPONATRAEMIA
• ACTH: CUSHING syndrome
• parahormone, PTH related peptide, PGE, cytokines: HYPERCALCAEMIA
• calcitonin: HYPOPCALCAEMIA
• gonadotropins: GYNECOMASTIA
• serotonin, bradykinin: CARCINOID syndrome

Question 17

common oncogenes in LC

Answer 17

KRAS
EGFR

Question 18

tumour suppressor genes that are lost in LC

Answer 18

p53

RB1

p16

multiple loci on chromosome 3 (lots of tumour suppressor genes)

Question 19

% of cases p53 lost in SCLC and NSCLC

Answer 19

SCLC 90%

NSCLC 50%

Question 20

most prominent genetic alteration in LC

Answer 20

EGFR mutations

Question 21

targeted therapies in NSCLC to target EGFR?

Answer 21

EGFR inhibitors

-> TKIs

Question 22

How does EGFR drive cancer growth?

Answer 22

• activated oncogene
• drives cancer growth
• decreases apoptosis
• increased angiogenesis

Question 23

TKIs and MAB used in NSCLC

Answer 23

Erlotinib

Gefitinib

Osimertinib

Cetuximab (MAB against EGFR)

Question 24

How does cetuximab work?

Answer 24

• binds to outside of EGFR
• stops EGFR from dimerising
• inhibits KRAS
• slows down EGFR signalling & cellular growth
• leads to cell apoptosis

Question 25

When does cetuximab become ineffective?

Answer 25

* if there's mutant KRAS * it becomes ineffective * cancer cell will survive and proliferate

Question 26

1st line Tx for NSCLC

Answer 26

* initially cetuzimab * when that fails use TKIs * 1st TKI = erlotinib

Question 27

How does erlotinib work?

Answer 27

* TKI * prevents EGFR phosphorylation * inhibits MAPK * tumour regression * resistance in 10-14 mths

Question 28

What mutation causes erlotinib resistanace?

Answer 28

T790M mutation

Question 29

Where does T790M mutation occur?

Answer 29

in the ATP binding pocket

Question 30

most common cause for TKI resistance (erlotinib, gefitinib, afatinib)

Answer 30

T790M mutation

Question 31

Tx for T790M mutation

Answer 31

* Osimertinib (Targrisso) * can bind to EGFR T790M * binds to the mutated R

Question 32

advantage with Osimertinib (Tagrisso)

Answer 32

* doesn't bind to WT (wild type) EGFR * only effects cancer cells and not normal cells

Question 33

What type of drug is Osimertinib (Tagrisso)

Answer 33

irreversible EGFR-TKI

Question 34

resistance mechanisms to Osimertinib (Tagrisso)

Answer 34

1. MET-amplification 2. EGFR C797S mutation 3. HER2-amplification, PIK3CA and RAS mutations

Question 35

EML4-ALK marker in NSCLC

Answer 35

ALK - R EML - structural protein NSCLC: genetic mutation activates ALK, leads to hyperphosphorylation & activation genetic change forms a fusion protein: - ALK fuses to EML4 - EML4-ALK fusion protein drives the protein fxn EML4-ALK activates proliferation -> 2 separate genes forming 1 gene

Question 36

problem with EML4-ALK fusion protein

Answer 36

* it bypasses EGFR blockade * inc proliferation and cell cycle * dec apoptosis

Question 37

TKI to target EML4-ALK

Answer 37

Crizotinib Alectinib

Question 38

drug used in LC if it has Ras mutation (G12C mutation)

Answer 38

Sotorasib (Ras inhibitor)

Question 39

examples of immunotherapy that inhibit PD1 and activate the immune system to attack tumours producing antigens

Answer 39

Pembrolizumab (Keytruda) Nivolumab (Opdivo)

Question 40

Why can tumour cells express PD1?

Answer 40

to suppress T cells

Question 41

PD-L1 inhibitors in LC

Answer 41

* tumour cells express PD-L1 to suppress T cells (PD-1 on T cell) * PDL = programme death ligand * PD-L1 inhibitors bind to PD-L1 and stop it binding to T cell * activate immune system to attack tumours