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Gene Expression Analysis for targeted Chemotherapy in Lung Cancer Patients PF-00299804 Robert J McKenna Jr. MD Robert J McKenna Jr. MD Head, Thoracic.

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Presentation on theme: "Gene Expression Analysis for targeted Chemotherapy in Lung Cancer Patients PF-00299804 Robert J McKenna Jr. MD Robert J McKenna Jr. MD Head, Thoracic."— Presentation transcript:

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2 Gene Expression Analysis for targeted Chemotherapy in Lung Cancer Patients PF Robert J McKenna Jr. MD Robert J McKenna Jr. MD Head, Thoracic Surgery Cedars Sinai Medical Center

3 Stage of Lung Cancer at Diagnosis- SEER Data

4 Adjuvant Chemotherapy No clear supportive data in Stage 1 Benefit seen in tumors greater than 4 cm Statistically significant benefit in Stage II and Stage IIIA Benefit all with cis- platin based chemo.

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6 Schiller JH. NEJM 2002; 346:92-98 Chemotherapy Doublets for Lung Cancer Treatment

7 Lung Cancer Chemotherapy Overall, any doublets have about a 40% response rate –That means 60% chemo given has no clinical response Adjuvant treatment increases survival 5-10% –That means 90% given with no change in survival

8 Lung Cancer Chemotherapy Future of lung cancer chemotherapy –Get better drugs There is some benefit from current drugs –Individualize treatment for patients

9 EGFR Inhibition The epidermal growth factor receptor is on the surface of cells. It transmits signals to the cell, including to grow and divide. Erlotinib has shown benefit in NSCLC. Overall magnitude of the benefit is small. Magnitude of benefit in responders is high.

10 Primary Tumor Work Tissue is obtained RNA is evaluated in the laboratory to ensure samples are of high quality Microarray analysis is performed using the Agilent system Molecular data is correlated with clinical data and patient outcome

11 Cy3Cy5 22,000 spots each containing a 60mer representing a known gene. The two probes hybridize to the spots in proportion to concentration of the specific RNA in each probe. mRNAs AGILENT MICROARRAY PLATFORM 1. Pre treatment core vs tumor reference 2. Pre- vs post 3. Post-vs pre- Fluor reversal

12 RNA extraction of Lung Tumors S RIN 9.3 S RIN 9.0 S RIN 9.4 S RIN N/A

13 Lung Tumors: Cluster All Probes 22,000 Genes Significantly Changed 337Tumors337Tumors Normals

14 Keratin Expression in 337 Lung Tumors 337 Tumors Kerati ns

15 Krt5/6, 14/16 Positive Lung Tumors 37 tumors (11%)

16 Squamous Lung Tumors on Cluster 337Tumors337Tumors Agilent 44K Chip

17 Neuroendocrine Tumors on Cluster 337Tumors337Tumors Agilent 44K Chip

18 Conclusions from primary samples High quality RNA has been obtained from nearly all of the samples Clear molecular subtypes can be found Data correlating gene expression with patient outcome will be available soon

19 Cell Line Collaboration We are evaluating novel compounds in a panel of 60 NSCLC cell lines Correlate cell line data with the data from primary tissue For a pre-surgical study, we selected the irreversible pan-HER inhibitor PF

20 Clinical Trial A presurgical study to evaluate molecular changes that occur in human non- small cell lung cancer tissue after short term exposure to PF

21 Lung Mass Diagnostic Biopsy Surgery Appropriate Additional Therapy Appropriate Follow-Up Assess Response to any Further Therapy 5-11 days of drug

22 Clinical Trial Evaluate molecular changes with chemo Evaluate changes in cell metabolism with chemo

23 Future of Lung Cancer Chemo Individualize treatment based upon a patients tumor markers or gene analysis

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