This special focus is jointly sponsored by the Center for Discrete Mathematics and Theoretical Computer Science (DIMACS), the Biological, Mathematical, and Physical Sciences Interfaces Institute for Quantitative Biology (BioMaPS), and the Rutgers Center for Molecular Biophysics and Biophysical Chemistry (MB Center). This meeting is also sponsored by The Center for the Development of a Virtual Tumor (CViT), and The National Cancer Institute's Integrated Cancer Biology Program.
Title: Multiscale cancer modeling
This talk will focus on modeling cancer as a complex dynamic, multiscaled biosystem where macroscopic behavior is determined by microscopic cell-cell interaction that in turn is guided by dynamics on the sub-cellular gene and protein level.
Cancer can be viewed as the loss of cooperative cell behaviors that normally facilitate multicellularity, including the formation of tissues and organs. The talk will describe a three-dimensional simulation called CancerSim which implements the hallmarks of cancer originally proposed by Hanahan and Weinberg. The talk will describe CancerSim and some preliminary simulation experiments that investigate the dynamics and interactions of the hallmarks.
Title: What do we learn from monitoring tumor growth?
Systematic longitudinal measurements of tumor growth are often neglected in recent clinical literature. Nevertheless, both in vitro (multicellular tumor spheroids or MTS) and in vivo monitoring of tumor growth enables unexpected insights on the interplay between the tumor itself and its surrounding host. By using the concept of Phenomenological Universality recently proposed, it is possible to observe that multi-passaged tumors in the rat grow according to different classes, which reflects the progressive ability acquired by the tumor of invading the host. Mathematically, the occurrence of higher order terms implies the appearance of new dimensionalities, generally expressed by power laws. Moreover, data from MTS and experimental in vivo tumors show that the power law exponent may change in time, reflecting the underlying feeding mechanism and its evolution. The cases of the invasive glioblastoma and of experimental tumors monitored throughout angiogenetic processes are a few examples. Finally, the potential impact of these results to cancer therapies, and mainly to radiotherapy, will be discussed.
Cell fate decisions and the epigenetic landscape
An important conceptual framework for understanding how genetic mutations, and in particular, non-genetic but stable changes contribute to tumorigenesis is the old idea that cell behavior takes place on an "epigenetic landscape", in which cell fates are attractors. This talk presents experimental evidence that the differentiated state in myeloid cells may in fact be attractors of the genomic gene regulatory networks and that binary cell fate decisions take place at "watersheds" in the epigenetic landscape. Implications for tumorigenesis, such as enlargement of the basin of attraction of the proliferative state will be discussed.
Title: Cancer as somatic evolution
Even though much progress has been made in main stream experimental cancer research at the molecular level, traditional methodologies alone are insufficient to resolve many important conceptual issues in cancer biology. For example, for the most part, it is still unknown how cancer originates, what drives its progression, and how treatment failure can be prevented. In this talk, I will describe novel mathematical tools which help obtain new insights into these processes. I will also show how the mathematical insights are combined with experimental studies through collaborations with cancer biologists. The main idea is to study cancer as an evolutionary dynamical system on a selection-mutation network. I will discuss the following topics: Stem cells and tissue architecture; Cancer and aging, and Drug resistance in cancer.
Title: Models of clonal expansion and wound healing in carcinogenesis
The process of carcinogenesis is characterized by genetic instability and clonal expansion of genetic variants. Mutant clones have been observed to have spread over large portions of organs. How the clones are able to disrupt tissue architecture barriers to expand is unknown. We are using agent-based, spatially structured models of carcinogenesis to explore the effects of wounding and adaptive mutations on clonal expansion. I will discuss a newly recognized mechanism for generating clonally related multi-focal lesions in epithelia that was discovered with the models. How clones expand in neoplasms has clinical significance for cancer prevention and therapy.
Title: Instability in the cancer process
Cancer is an example of a complex, robust system. Gene instability is a property of cancer cells and it leads to a high diversity in tumor cell population. Instability allows us to explore gene expression profiles that can cause a growth benefit of cancer over normal cells. However, an excess of instability could cause a catastrophic error resulting in non viable tumor cells. Here, we explore the role of genetic instability in tumor progression. We use analytical and computational models of unstable tumors to evaluate the impact of increasing levels of instability in cancer progression.