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.

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?

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

2. Genomic Instability

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

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

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

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.

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