Question 1: EMT in Invasion/Metastasis?

Our text emphasized epithelial-mesenchymal transition (EMT) as a major driver for invasion and metastasis. Though many researchers in the cancer field have adopted this hypothesis, skepticism remains, especially amongst tumor pathologists. EMT, though a fitting and sound explanation for the invasion-metastasis cascade, is difficult to observe since mesenchymal cells in vivo resemble populations normally found within the stroma. Yet, a search for EMT and cancer on Pubmed will yield thousands of entries within the last decade. Is EMT the key to understanding and potentially blocking metastasis, or do too many questions remain unanswered?

In addition to the perspective presented in the text, read the articles by Tarin and Thompson, and argue whether or not you think EMT is responsible for invasion and/or metastasis of tumors.

Question 2: Tumor Dormancy - What triggers the switch?

The mechanisms that "trigger" micrometastases to develop into macrometastases (which can be clinically detected) are still poorly understood. However, elucidating these pathways could offer valuable insights into the long term treatment of cancer patients. In this Unit we learned about the possible (and likely cooperative) role of intracellular genetic changes and the immune system in this process. Interestingly, the efficiency of this process is believed to be very low (indeed, many patients exhibit micrometastases that never develop into full blown clinical metastases).

Argue which mechanism has a strongerinfluence on the outcome of colonization. What do you think is the main driver leading to the development of macrometastases from micrometastases?

Question 3: Cancer in Immunocompromised Individuals

Evidence that the human immune system can protect us from cancer (at least to an extent) is exemplified by the increased incidence of cancer in immunocompromised individuals. This is a fairly recent observation due to 1) the increased population of individuals receiving organ transplants (who often take immunosuppressive drugs to prevent rejection for extended periods of time), and 2) the increased longevity of populations infected with HIV. Based on your understanding of the role the immune system plays in the elimination or suppression of neoplastic cells, discuss one reason why immune compromised individuals develop higher rates of cancer. Be specific (i.e. differentiate between virally and non-virally induced cancers). Keep in mind that this is an ongoing discussion, please do not try to cover everything in one post

Why do immunocompromised individuals have a much higher incidence of cancer (be specific)?

Question 4: Write your own

• Explore the invasion-metastasis cascade and discuss relevant molecular pathways hypothesized to control this cascade such as epithelial-mesenchymal transition.
• Evaluate the role the innate and adaptive immune system in controlling cancer formation and progression.
• Compare and contrast the tumor promoting and inhibitory capabilities of the immune system.
• Discuss immunotherapies for cancer treatment and evaluate the benefits and challenges surrounding these treatment strategies.