high incidence of lung cancer in asians not due to second-hand smoke
TRANSCRIPT
Achieving Precision Medicine for Lung Cancer in Asians
Precision Medicine: Targeted therapies elicit high response rates in molecularly defined cancers
Bcr-Abl
ChronicMyeloid Leukemia
EGFR*
EGFR-mutatedNon-Small Cell Lung Cancer
ImatinibErlotinib/GefitinibSpecific to Asia
EGFR mutation more frequent in Southeast Asian populations
BIM deletion polymorphism confers resistance, and found in Asians
Lung Cancer
Asians have higher non-smoking lung cancer than Westerns
Why do Asians have higher non-smoking lung cancer than Westerns?
Is it due to second-hand smoke?
• Are smokers and never-smokers tumor profiles similar?
• If yes, then second-hand smoke is cause of higher incidence.
• Different from Western countries?
• Something unique to Asian causing differences?
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• Sequenced 30 genomes of lung cancer patients
Whole-genome sequencing of asian lung cancers: second-hand smoke unlikely to be responsible for higher incidence of lung cancer among Asian never-smokers.Cancer Research 2014 Nov 1;74(21):6071-81.
Distinct mutation signatures between smokers and non-smokers
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Asian non-smokers look like European non-smokers (high G.C > A.T)Asian smokers look like European smokers (high G.C > T.A)
High incidence of lung cancer in Asian non-smokers is unlikely due to second-hand smoke
All the never-smokers
Contains only smokers
G.C > A.T observed before for nonsmokers
G.C > T.A. seen before for smokers
Distinct mutation signatures between smokers and non-smokers
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Asian non-smokers look like European non-smokers (high G.C > A.T)Asian smokers look like European smokers (high G.C > T.A)
High incidence of lung cancer in Asian non-smokers is unlikely due to second-hand smoke
All the never-smokers
Contains only smokers
~1/2 of ex-smokers/smokers classified with never-smokers
Evidence #1: Some smokers have a nonsmoker molecular signature
Evidence #2: Some smokers have a nonsmoker molecular signature
Evidence #3: Some smokers have a nonsmoker molecular signature
• Half of the smokers/ex-smokers have a nonsmoker molecular signature
• Smoking status insufficient
Mutations (such as EGFR) drive cancer regardless of smoking status
Smokers with non-smoker signature
EGFRDoes not have EGFR
Lung Cancer Treatment
chemotherapy
LungCancer
SequenceEGFR
EGFR mutant
EGFR wildtype
gefitinib
chemotherapy
First line of questioning is phenotype, then later genotype
Phenotype << Genotype
Conclusion
• Smokers can have a non-smoking molecular signature
• Sequence for EGFR mutation, regardless of smoking status
• Molecular signature confirms what’s already in practice in Singapore and Japan