Question #1: Telomerase and Cancer Stem Cells
1. Telomerase and cancer stem cells: the future of cancer treatment?
Telomerase is an attractive target since 85% - 90% of tumors express telomerase (while normal cells express little to no telomerase). One paradigm in this model is the "cancer stem cell" hypothesis. Cancer stem cells (or tumor-initiating cells with stem-cell like properties) can self-renew, as well as give rise to heterogenous tumor cell populations (essentially, they are believed to be responsible for the formation and maintenance of the tumor). If these cells are indeed "stem-like" they also divide more slowly, and presumably express telomerase (like normal stem cells).
Based on your reading, and information from Shay and Wright, 2006 (below, specifically pages 5 - 6), do you think combination therapy (chemotherapy + telomerase inhibitors) are effective? What challenges may hinder our understanding of these pathways (and therefore development of these treatments)?
(Refer to Shay and Wright 2006 and Tan et al. 2006)
Question #2: Why Don't Whales Get More Cancer?
2. Why don't whales get more cancer?
It has been observed that humans have shorter telomeres than mice. Do telomeres function differently in mice because they have less cells and shorter life spans (therefore, less cell divisions)? Do humans need more anti-cancer mechanisms because of this (more cells, more divisions, a higher incidence of mutation rate in more tissues can lead to increased cancer). By this logic, very large organisms that also display longevity should be more susceptible to cancer (such as whales), but this is not the case. Peto's paradox states that there is no association between cancer incidence and body mass and longevity in wildlife species. Studying the mechanism behind this paradox may provide answers to cancer prevention rather than treatment in humans.
Is solving Peto's paradox the key to cancer prevention? Integrate topics from this unit (information about telomere length, regulation of angiogenesis, tumor promoters) and/or previous units (metabolic rate, number of tumor suppressor/oncogenes in various species) to discuss one hypothesis explaining Peto's paradox that could be important to our understanding of tumor biology.
(Refer to Roche et al. 2012 and Caulin and Maley 2011
Question #3: Cancer as a Systemic Disease
3. Cancer as a systemic disease: how should we approach the development of new treatments?
Thus far, we have viewed tumors as localized abnormalities in a particular tissue that exploit intrinsic biological processes for their own gain (disregarding metastasis for a moment, which we will explore in Unit 6). However, examining the process of angiogenesis has painted a picture of systemic interactions of tumor cells with other parts of the body (i.e. bone marrow, blood vessels, etc). Indeed, in some cases, cancer therapeutics are evolving to target supporting networks as opposed to rapidly dividing neoplastic cells (i.e. stroma, cancer stem cells, and endothelial cells).
How can cancer be viewed as systemic disease, even if it is localized to a particular tissue or organ? How does this influence the development of treatments (or even preventative therapies) for cancer? Choose a specific mechanism/pathway to discuss.
(Refer to Schafer and Werner 2008)
Question #4: Write your own!
Don't like these questions? Write your own! (but please stay on topic) Your original question should address at least one of the articles from the additional reading list.