Course Meeting Times
Lectures: 1 session / week, 2 hours / session
Prerequisites
There are no strict prerequisites, but some knowledge of genetics, biochemistry, and cell biology is expected. Students are recommended to have taken at least one of the following courses:
Course Description
Tumors grow and evolve over many years or decades, sometimes progressing to the lethal stage of metastasis, in which cancer cells that have left the primary tumor establish new growths in organs throughout the body. Metastatic disease is responsible for the vast majority of deaths associated with cancer and is considered incurable, yet our understanding of how metastases arise is still developing. The path from a normal cell to a primary tumor, driven by genetic mutations, has been extensively mapped over the past 40 years and is reasonably well understood.
But how do some primary tumors progress to the metastatic stage? Accumulating evidence suggests that epigenetic changes, which are not driven by particular mutations but instead are somehow hijacked from latent developmental programs, play an essential role in enabling tumor cells to form metastases. These mechanisms change both the intrinsic characteristics of tumor cells and their interactions with surrounding “normal” cells, reshaping the microenvironment, at both the primary and metastatic sites, to favor tumor growth and escape from immune attacks.
We will begin this course by introducing various concepts and models that have been proposed to explain how cancer cells disseminate from a primary tumor to distant anatomical sites. Next, we will turn our attention on two critical factors that influence cancer metastasis: heterogeneity of and plasticity among neoplastic cells in the tumor (the seeds) and components of the tumor and tissue microenvironment (the soil). We will explore these frontiers through analysis and discussion of relevant primary research articles, with an emphasis on mechanisms of metastasis that can be applied across different cancer types. Students will gain a broad understanding of the field of cancer metastasis, including state-of-the-art techniques that are being used to address pressing questions in the field. There will also be an opportunity for a remote “field trip,” where students will virtually visit with cancer scientists working at a local biotech and pharmaceutical company. Most importantly, through these discussions, students will develop the ability to critically analyze research papers and to logically design experiments to explore scientifically important questions.
Format
This course will meet once per week for two hours. Each week we will discuss two scientific articles, critically analyzing the experimental design, methodology, results, and conclusions of the papers. Students are expected to have read the articles in advance of class and should be prepared to discuss them in detail with the group. In addition to our weekly discussions, there will be one midterm written assignment and one final oral assignment.
Objectives
This goal of this course is to introduce students to the critical reading of primary scientific articles in the field of cancer metastasis. Through this course students will:
- Learn to critically evaluate the design, results, and conclusions of primary scientific literature.
- Become familiar with experimental approaches and methods used to study cancer metastasis.
- Develop an appreciation for the key steps and biological determinants of metastatic progression.
- Independently write and present critiques of scientific articles.
Grading and Requirements
The course will be graded as pass/fail. Students are expected to attend every class, come prepared to participate in discussions, and complete the midterm and final assignments in a satisfactory manner.
Calendar
| week # | topics | key dates |
|---|---|---|
| 1 | Introduction | |
| 2 | Epithelial-Mesenchymal Transition and Dissemination from the Primary Tumor | |
| 3 | Cancer in Transit: Dynamics and Behaviors of Circulating Tumor Cells (CTCs) | |
| 4 | Stromal Support of Dissemination | |
| 5 | EMT Plasticity and Metastatic Colonization | |
| 6 | Cancer Stem Cells | |
| 7 | Genetic Heterogeneity and Evolution of Metastatic Disease | Written assignment due |
| 8 | Field Trip (virtual), to Agios | |
| 9 | Determinants of Metastatic Tropism | |
| 10 | The Metastatic Niche | |
| 11 | Systemic Effects and the Pre-metastatic Niche | |
| 12 | Interactions Between Dormant DTCs and the Immune System | |
| 13 | Oral Presentations and Closing Remarks | Oral presentation due |
