Two types of biomarkers used in lung cancer
- prognostic biomarkers
- outcome w.o therapy
(who is at increased risk of relapse?)
- predictive biomarkers
- outcome w. therapy
(who will benefit from therapy?)
Lung cancer at time of diagnosis statistics
-lung cancer is usually diagnosed at a very late stage
Majority of lung cancers are what type?
Non-small cell lung cancer NSCLC (85%)
vs the measly SCLC
What are molecular targeted therapies?
Agents that work against patient’s particular effed up biochemical pathway
-used to stimulate immune system
How to select patients in order to give the right treatment to the right patient?
Look for predictive biomarkers .
- personalized medicine targeting:
1. EGFR mutation
2. ALK gene rearrangement (fusions)
3. PDL1 Immunotherapy
(target the therapy towards the damn problem. - no longer one size fits all)
How do we implement molecular targeted therapies in treatment of lung cancer?
If there is a problem, target the therapy towards it. Duh.
What is role of EGFR signaling in lung cancer?
significant in carcinogenesis: affects angiogenesis/proliferation/anti-apoptosis
What are some drugs used to treat lung cancer? What do they do?
Epidermal growth factor receptor inhibitors:
(these should look familiar)
- Tyrosine kinase inhibitors:
- Erlotinib, gefitinib, afatinib
- Monoclonal antibodies
- PD1: stimulates T cell
- Cetuximab and necitumumab (not approved)
Next gen sequences can detect what?
- mutation detections
- DNA copy number
- translocations/gene fusions
- RNA seq
Status of screening lung cancer
Screening trials for early stage disease/prevention:
-look for smokers/high risk groups –> screen the sh*t out of them
-can reduce lung cancer mortality 20% with low dose CT scan!
but LOTS of false positives 95% so need to use biomarkers
3 ways to affect EGFR
- Ligand overexpression
- Receptor overexpression
- Mutation near binding pocket
Which exon has the most mutations for EGFR?
What is crossover phenomenon and what does it affect?
Individuals may no longer be responding well to a drug, so they switch to another drug. This would be a problem if you were studying effects of a drug.
Ie. People switch over drugs from chemo to TKIs that they use for lung cancer and therefore the overall survival is diluted (looks the same). You aren’t seeing the true effect of that drug. Your drug may not be as effective bc people switched drugs before they die.