ABSTRACT
This chapter discusses the concepts of modularity, retroactivity, and pathway integration, and delineate some of the outstanding questions that we believe should be prioritized for modeling in cancer. It postulates that new breakthroughs in our understanding of cancer are needed to overcome these fundamental challenges. The chapter poses that a better approach is to understand how information is transferred within a cell and integrated across cells in tissues, particularly understanding the coding, decoding, transfer, and translation of information in cancer, insights that may likely be gained through modeling approaches. It hypothesizes that subtle, indirect interactions of this sort, which can be viewed as a failure of insulation and modularity, may be an important cause of aberrant signaling in cancer; inappropriate cross talk of this sort has already been implicated in several cancer types. The chapter defines preclinical cancer stages as those detectable changes at the cellular and tissue levels that indicate dysregulation of signal integration that may predispose invasive cancer.
