Robert Getzenberg (JHU) & Don Coffey (JHU) : Additional Material

These three articles will flow towards the metastatic aspects of the concepts in our discussions. 

 

We understand that Dr. Michor is attending the meeting but wanted to include one of the papers on which she is an author since it raises what we feel is a very important concept.  This manuscript on quasispecies connects chromosome structure to evolution and cancer and introduces some mathematical issues.  The recent paper on pattern recognition will provide a link to the physics on this topic. We are sure that Herb Levine will apply his vast experience to this problem.  The last of the papers is an old review on the tissue matrix that sets the background for the structural aspects of what we will discuss. 

Background Papers:

• Reaction-Diffusion Model as a Framework for Understanding Biological Pattern Formation
• Genetic instability and the quasispecies model
• The Tissue Matrix: Cell Dynamics and Hormone Action

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?