Qualifying Exam Questions

June 2009

1. Select two molecular events of your choice and describe their contribution to the malignant phenotype in melanoma.
   
   -- Menasche Bar Eli, Ph.D.
   
   
2. Autophagy has been implicated in cancer cell survival and death. Decide for yourself which makes more biological sense to you and defend why you think so.
   
   -- David J. McConkey, Ph.D.
   
   
3. Tumorigenesis has been proposed to be a multistep process driven by an accumulation of genetic and epigenetic events that result in the acquisition of six common capabilities associated with the cancer phenotype.
   
   a. What are the six common acquired capabilities (“Hallmarks”) that are associated with the cancer phenotype? Briefly describe each of their characteristics.
   
   b. Provide a clinical example that illustrates the multistep tumorigenesis process.
   
   c. What role does genetic instability play in the multistep tumorigenesis process?
   
   d. Give an example of how one might assess the degree of genetic instability in a biopsy from a tissue at risk for developing cancer?
   
   -- Walter N. Hittelman, Ph.D.
   
   
4. a. DRAW a model diagram to describe Knudson’s Two Hit Hypothesis of Cancer.
   
   b. INCLUDE in the model diagram and briefly describe five ways in which the second hit can occur in cancer development according to Knudson’s model.
   c. Why is Knudson’s Two Hit Hypothesis so important to our understanding of cancer development?
   
   -- A. M. Killary, Ph.D.
   
   
5. Several lectures in this course have highlighted the complex processes required for a tumor cell to become metastatic. Recent work in the field has suggested that both host and tumor cells play intimate roles in this process. Focusing on a tumor cell acquiring the invasive phenotype, give one example EACH of how the tumor cell itself and host stromal cells might contribute to this process.
   
   -- Gary E. Gallick, Ph.D.
   
   
6. Describe DNA damage responses in mammalian cells.
   
   -- Shiaw-Yih Lin, Ph.D.
   
   

7. a. Breast cancer is the most commonly diagnosed cancer in women in the USA. If you were responsible for testing a novel drug that you anticipate will prevent breast cancer, how would you select women at highest risk of developing invasive breast cancer, and therefore most likely to benefit from the drug? What agents have already been tested in breast cancer prevention trials?

   b. Molecular-targeted therapies have been used with some success for treating breast cancer. Describe at least two examples of targeted therapies that are being used for breast cancer. Briefly discuss the mechanism(s) of action of the therapy.
   
   -- Janet E. Price, Ph.D.
   
   

8. Describe the pathogenesis of metastasis and how you can prevent the establishment of a metastasis?
   
   -- Isaiah J. Fidler, D.V.M., Ph.D.
   
   
9. Recorded historical observations of immunity to infectious diseases date to nearly 2,500 years ago, when Athenians observed that survivors of the plague often were less vulnerable to reinfection. This illustrates the concept of "immune memory," or life-long specific immunity, which also has been shown to occur against some tumor antigens. These observations, and others like them, inspired the idea that immunity to cancer could be developed as a potent treatment for cancer patients. Describe the potential advantages and disadvantages of tumor immunotherapy over traditional cytotoxic chemotherapy.
   
   -- Jeffrey Molldrem, M.D.
   
   
10. Please describe in detail the three stages in chemical carcinogenesis.
    
    -- Shiaw-Yih Lin, Ph.D.
    
    
11. DNA repair mechanisms are highly conserved, reflecting their importance to survival of cells and organisms from E. coli to elephants. Consider three mechanisms of DNA repair. Describe the biochemical nature of the DNA damage that is the focus of each mechanism, the proteins that participate in each mechanism and syndromes or specific diseases that arise when mutations affect their function.
    
    -- William K. Plunkett, Ph.D.
    
    
12. What is a stem cell? What is "self-renewal capacity"?
    
    -- Zeev Estrov, M.D.
    
    
13. Describe in detail the role of VEGF and VEGF family members in induction of tumor angiogenesis.
    
    -- Lee M. Ellis, M.D.
    
    
14. Please describe why cancer chemoprevention is important and what could be the strategies for developing effective cancer chemopreventive agents.
    
    -- Ho-Young Lee, Ph.D.
    
    
15. Explain (list) the pathogenesis of a metastasis. What are the requirements for establishment of a metastasis and what are the principles of the “seed and soil” interactions.
    
    -- Isaiah J. Fidler, D.V.M., Ph.D.
    
    
16. What experiment would you perform to confirm that a single cell is a hematopoietic stem cell? Please describe, briefly.
    
    -- Zeev Estrov, M.D.
    
    
17. Discuss the possible reasons for the failure of clinical trials with matrix metalloproteinase inhibitors in cancer. What therapeutic avenues, if any, could be pursued for using protease inhibitors in cancer treatment?
    
    -- Douglas D. Boyd, Ph.D.
    
    
18. Why does cancer arise in people with functioning immune systems? How can the immune system be manipulated to treat malignancies?
    
    -- Laurence J. N. Cooper, M.D., Ph.D.
    
    
19. Epigenetic changes are now thought to be equal partners with genetic changes in causing the cancer phenotype. Please describe epigenetic alterations in cancer and the reasoning behind equating them with genetic changes.
    
    -- Jean-Pierre Issa, M.D.
    
    
20. The identification of putative cancer stem cells in solid tumors has enormous implications for basic studies in cancer biology and clinical intervention. Discuss the evidence supporting the existence of cancer stem cells, the evidence against this concept and how repopulation of these putative cells might alter paradigms of cancer therapy. You may discuss the concept in general, or use a particular tumor type to support your argument, but a complete discussion of the concept is expected.
    
    -- Gary E. Gallick, Ph.D.