English work : 24 hours : 6 pages

Each question is worth 16 points.  Your complete answer to each question (this includes all subparts of the question) should be no longer than 2 pages double-spaced.  I will consider your answer complete at the end of the 2^nd page and not read beyond this length.  Please answer all three questions – there is no extra question to drop on this exam.  Your exam should be no more than 6 pages in total, outside of the exceptions noted below.

Please cite references (text for this course, original primary literature, and/or review articles) to support your answer. References should follow the reference style of “Uniform Requirements for Manuscripts Submitted to Biomedical Journals” (http://www.nlm.nih.gov/bsd/uniform_requirements.html) and be cited where they are used, not just in a running bibliography at the end of the exam.  References do not count in the page length.  Figures may also be included and do not count in the page length, but must be adequately explained in the text.  Formatting for your document should include 12-point font and 1 inch margins.  

1. Multistep Tumorigenesis

We know tumor progression moves forward in a multistep fashion.  With this knowledge:

a.)    Explain how clonal evolution of tumors resembles Darwinian evolution.  (4 points)

b.)    What evidence do we have from population/epidemiology studies, manipulation of animal models, cells in culture, and tumor genomes to support the multistep progression? (8 points, 2 for each example)

c.)     To what extent do cancer cells remain dependent on the initial mutant allele vs. other mutant alleles taking over later in progression? (4 points)

2. Genomic Instability

a.) Describe how defects in DNA repair contribute to tumorigenesis, and include a specific example. (8 points)

b.) How are these deficiencies in DNA repair being exploited for therapeutic purposes, again with a specific example? (4 points)

c.) How does genomic instability present major issues for cancer treatment? (4 points)

3. Tumor immunology

a.) How is the immune response to human tumors suppressed?  Please provide one example each for how the immune cells themselves suppress a response and how the cancer cells contribute to immune response suppression. (8 points, 4 for each example)

b.) What strategies are being used to overcome each (cancer cell initiated and immune cell initiated) example given above? (8 points, 4 for each example)