Chuck Drake, Johns Hopkins University

Three Problems:

• Do cancer cells metastasize as single cells, as clusters of tumor cells, as clusters of tumor and myeloid cells, or as fusions between tumor cells and macrophages?
• What is the relative role of passive (fluid dynamic) versus active processes (diapedesis, extravascation) in the establishment of metastases from tumor cells circulating in the vascular or lymphatic compartments?
• At what stage in the metastatic process are tumor cells most susceptible to immunological intervention? 

Background Papers:

• Active versus passive mechanisms in metastasis: do cancer cells crawl into vessels, or are they pushed?
• Integrins in cancer: biological implications and therapeutic opportunities
• Fusion of tumour cells with bone marrow-derived cells: a unifying explanation for metastasis
• Circulating Tumor Cell Clusters in the Peripheral Blood of Colorectal Cancer Patients

Robert Getzenberg, Johns Hopkins University

Three Questions:

• Metastatic cancer cells have amplified evolutionary capabilities that allow them to develop resistance to therapeutic approaches.  This may be enhanced by niches/microenvironments being emptied by “sensitive” populations that do not survive.  What role do physical and/or structural properties play in the development of resistance and how can modification of these by used to hinder the evolution of cancer?
• The concept that cancer cells metastasize as single cells may not be correct.  Groups of cancers cells along with what appear to be perhaps supporting players have been identified.  Do cells, other than the tumor cells themselves, “travel” with the cancer cell and aid in the development of metastatic sites?  If so, are they from the site of origin or are they recruited from other sources?  Can we image these?
• It appears that heat can be used to increase the sensitivity cancer cells to other forms of therapy and that the price that the cancer cells pays for being so able to develop resistance to therapy is a sensitivity to microenvironmental stresses.  What physical properties of the cells have been altered that creates this sensitivity to stresses?  

Don Coffey, Johns Hopkins University

Central Question:

Why is there so much variation (heterogeneity) within solid tumors in relation to  cell structure and function and how might this relate to energy, information transfer, and self-organization?