Educational Level:

Roadmap Objectives:

• • Article: Recommendation for a human cancer genome project: Report of working group on biomedical technology (2005).http://www.genome.gov/Pages/About/NACHGR/May2005NACHGRAgenda/ReportoftheWorkingGrouponBiomedicalTechnology.pdf
  • Content area/major concepts: I envision using a paragraph from this recommendation that eloquently describes the purpose of this module. Students will learn about the nearly failed clinical trial using Iressa to treat NSCLC. This paragraph is also very powerful because it is coming from a governmental working group on biomedical technology. This can lead into a great discussion about governmental funding for research as well as the design of clinical trials.
    
    EGFR signal transduction pathway; lung cancer; targeted drug therapy; clinical drug trial.
  • Methods or technology used to obtain data:
  • How the CREATE strategy was used: concept map; translation of sentences
  • Biggest teaching challenge: It will be difficult for the students to fully understand why this drug trial nearly failed since only 10% of the patients had positive results. It might also be challenging to have the students understand why the government is interested in cancer research. Students will learn about NSF and NIH funding. They will also learn about clinical drug trials via FDA.
• • Article: Lynch et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small cell lung cancer to gefitinib (2004). New England Journal of Medicine 350 (21) 2129-2139.
  • Content area/major concepts: I chose this paper because it was one of the first papers to identify specific mutations in EGFR in lung cancer patients who responded to the Iressa drug. This group used the tumor specimens from patients who either responded or did not respond at all to the Iressa drug trial to identify the reason why there was a subgroup of patients (10%) who responded so well to the drug.
    
    Content reviewed: types of point mutations; somatic compared to genetic mutations; components of a membrane tyrosine kinase receptor; EGF signal transduction pathway; biology of lung cancer; review of how a protein kinase inhibitor is used to block EGF signalling
  • Methods or technology used to obtain data: DNA isolation; PCR; sequencing; site-directed mutagenesis; recombinant DNA cloning; transfection; cell culture; western blot
  • How the CREATE strategy was used: I will follow the entire CREATE protocol steps for this paper by starting with just giving the students the introduction and having them make a concept map to ultimately doing the grant panel and then writing questions for the authors.
  • Biggest teaching challenge: It will take a lot of extra time teaching the students all of the methods used for the project. Some of those techniques should have been explained in previous classes. Students could have also used some of the simple methods in previous lab courses. I suspect that students will have difficulties understanding the details of the structure of EGFR and where the mutations are located. I also see that they might be challenged reading and annotating real tissue samples and then switching to cell culture studies.
• • Article: Paez et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy (2004) Science 304 (4) 1497-1500
  • Content area/major concepts: I chose this paper because it was the second paper to identify the specific mutations in EGFR in lung cancer patients who responded to Iressa drug. This group used tumor samples from 119 random NSCLC tumors, none who had documented treatment with Iressa. They also used lung cancer cell-lines that had known mutations in EGFR to see if they conferred Iressa sensitivity.
    
    Content reviewed: types of point mutations; somatic compared with genetic mutations; components of a membrane tyrosine kinase receptor; EGF signal transduction pathway; biology of lung cancer; review of how a protein kinase inhibitor is used; other signaling pathways
  • Methods or technology used to obtain data: DNA sequencing; cell culture; cell viability studies; westerns
  • How the CREATE strategy was used: I will have students create a concept map from the introduction. Then I will have them work on only 1 selected figure from the paper. For that figure, they will make a cartoon. They will also translate difficult sentences. They will annotate, write titles, and use the template to analyze. Though they will only work with one figure, I will still have them design future experiments and do the grant panel. I will also have them write a few questions for the authors.
  • Biggest teaching challenge: ince this paper is from Science, it will be difficult to fully use the CREATE method. In particular, students will have difficulty cartooning each figure as well as using the template for each figure. Regarding the content, students will have difficulty understanding the figures since they don’t have a methods section.
• • Article: Rafael Rosell Discusses EGFR Mutation Testing for Lung Cancer (2010) Science Watch **http://archive.sciencewatch.com/dr/nhp/2010/10novnhp/10novnhpRose/**
  • Content area/major concepts: At the end of the module, I want the students to learn how lung cancer patients are actually tested for the EGFR mutations. I think this will be useful for students to actually see the bench to bedside approach to medical care.
    
    Content Reviewed: mutations, translational research, EGFR, lung cancer
  • Methods or technology used to obtain data: Since this is a review about the primary article, the article does not discuss the methods. I will use the primary article to discuss the TAQMAN RT PCR method used to screen for the mutations.
  • How the CREATE strategy was used: For this paper, once we go over the technique, I will give students data from several patients’ mutations and have them then decide who gets to use Iressa. They will have to validate their explanation based on their knowledge about the mutations. I want the students to also write email questions for the authors of this primary paper. At the very end of this module, they will then have an opportunity to design a better clinical drug trial for Iressa . We will then have a grant panel to decide which trial FDA will approve.
  • Biggest teaching challenge:

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