Cancer Biology Questions
Question 1: A) What is the definition of a quantitative trait? Use the example of twin heritability model to explain how this underlying assumption is inaccurate.
B) Explain how the experiment with Agouti mice, demonstrates that the biology of gene x environment interactions is not additive.
Question 2: Design an experiment to look at the timing of MT1-MMP expression in stromal cancer in the tumor microenvironment in response to tumor growth, making use of small animal optical imaging system (i.e. IVIS). This experiment should include an orthotopic xenograft in a reporter mouse.
• Describe the tumor cells that you will use in this experiment. Consider characteristic such as the cell type and species.
• Explain where the tumor will be implanted and specifically how you will non-invasively monitor tumor progression over time using optical imaging.
• Describe the reporter mouse you would like to design to monitor MMT-MP1 expression in the host stromal cells surrounding the tumor.
• Explain which strain of mice you will use and why it was chosen. Consider characteristics such as color and immune status.
• Describe the gene that will serve as the reporter, how the expression of that gene will be regulated (think about the promoter) and how the reporter will be monitored over time using optical imaging.
• Explain the expected result and least one control for these experiments.
Question 3: Design experimental steps to identify potential genes whose transcriptional are in carcinogenesis of a population exposed to certain environment carcinogens (i.e. mineral dust). After the candidate gene markers are determined from your chosen experimental platform. Describe a second experimental plan to confirm your result using a different gene expression assay platform. Next, please list bioinformatic tools (databases) which can be used to confirm the differential expression patterns of the identified genes in cancer development and progression. Give a brief description of the steps taken in the analysis and anticipated results.
Question 4: Dr. Davis;
– How is metabolic activity reprogrammed in cancer?
Not all reprogrammed metabolic activities contribute equally to cancer. With many metabolic activities under oncogenic control, categorizing them based on whether they are transforming, enabling, or neutral can clarify the role of each activity in cancer biology and predict how it might be exploited in basic research and clinical oncology.
1: Transforming Activities: These activities directly contribute to cell transformation and blocking them might prevent tumorigenesis in susceptible patients or antagonize disease progression.
2: Enabling Activities: These activities are altered in cancer cells but are not involved in the transformation. They carry out conventional metabolic tasks such as supporting energetics, generating macromolecules, and maintaining redox state and are required for tumor progression
3: Neutral Activities: these activities are predicted to be poor therapeutic targets. Fluctuating nutrient access may cause activities to be required in some contexts and dispensable in others. Thus, confidently classifying an activity as neutral is challenging and requires definitive proof that loss of the activity does not impair tumor progression.
– What products are limiting for proliferation?
Targeting activities that supply limiting materials for proliferation is therapeutically attractive, especially if the pathways used are less important in normal proliferative tissues. Although several metabolic products have been proposed as critical outputs of cancer metabolism, which are rate-limiting for proliferation remains controversial.
Ex: ATP, NADPH, Nucleotide Synthesis, Products of the TCA Cycle, and Consequences of Electron Acceptor.
– What determines how different tumors use metabolism?
1: The Environment Can Affect Cancer Cell Metabolism
2: Cell Lineage Can Also Affect Cancer Metabolism
3: Interactions with Benign Cells Can Affect Cancer Cell Metabolism
– Should metabolism be considered during cancer progression?
Yes, it should be considered during cancer progression to supply tumor cells.
– Can cancer metabolism be exploited to improve therapy?
To target metabolism for therapy, limiting metabolic processes must be identified and understood sufficiently to target the process safely and select responsive patients. Using the classifications, transforming and/or enabling activities must be identified with an adequate therapeutic index.
Clinical experience with cytotoxic chemotherapy highlights the challenges that will likely confront new metabolic therapies. Many chemotherapies inhibit nucleotide metabolism.