Lung Cancer

Question 1

What is the function of prognostic biomarkers?

Answer 1

Predict outcome (survival) based on the natural course of the disease 
WITHOUT 
therapeutic intervention

Question 2

What is the function of predictive biomarkers?

Answer 2

They predict how specific disease markers will respond to specific therapy
i.e. Who will or will not respond to a treatment

Question 3

How are lung cancers classified?

Answer 3

Histology
MUTATIONS
(EGFR, HER2, etc)

Question 4

What are targeted therapies

Answer 4

Agents that work against specific biologic pathways

Question 5

What type of treatments are used for mutations in EGFR?

Answer 5

1. Tyrosine Kinase Inhibitors

2. Monoclonal antibodies

Question 6

What type of drug is Gefitinib?

Answer 6

1st tyrosine kinase inhibitor

• better than chemo b/c targeted
• decrease mortality by 52% (hazard ratio of .48)
• dramatic response (x-ray of tumor shrinkage)
• Increase progression free survival

Question 7

What type of therapy is cetuximab?

Answer 7

Monoclonal antibody theraby

Question 8

How are mutations identified in order to target therapies?

Answer 8

EGFR protein expression

EGFR gene copy number (FISH)

Question 9

How is Anaplastic lymphoma kinase (ALK) gene rearrangement identified?

Answer 9

FISH
ALK - protein expression
Fusion gene id in PCR 
(3% of lung cancers)
- this mutation results in chimeric proteins with constitutive kinase activity

Question 10

What is significant about ALK therapy?

Answer 10

Crizotinib
Response in patients who did not respond to chemo (waterfall plot)
- increase in median progression free survival

Question 11

What are the advantages of lung cancer screening tests?

Answer 11

20% reduction in lung cancer mortality (with lo dose CT)`

Question 12

What are the drawbacks of lung cancer screening?

Answer 12

90% of masses detected are benign
- diagnosis of benign mass can involve invasive and stressful follwo up

=> need to decrease false/ non-malignant positives (improved identification of screening population?)

Question 13

How does personalized medicine related to lung cancer?

Answer 13

• many sub-types, each with their own molecular characteristics -> >50% can be targeted by molecular targeted drugs (EGFR & ALK)
• molecular testing before treatment is crucial
  => molecular targeted therapy v. chemo v. combo