Cancer cells often remain quiescent for years of even decades. This fundamental, and still mysterious, property of cancer is the subject of the next workshop. Latency refers to the fact that cancer cells, or even small tumors of the sort that are detected in screening programs, may never progress to cause clinical symptoms. Dormancy describes the well-known phenomenon that, following the removal of a primary tumor, the same cancer may reappear years later in a more malignant form. Cancer latency and dormancy offer a clear challenge to the physical science and oncology program. If cancer is stabilized in a quiescent phase as a result of certain physical parameters in the micro-environment (e.g. pH, oxygen tension, pressure), then controlling those parameters may offer a way to extend the phase. A cancer that lies latent or dormant for many decades may cease to be a serious health issue.

Workshop Agenda

Participant List

There is a growing realization of the importance of oxygen in understanding cancer, combined with a serious effort to trace the evolutionary roots of cancer back to the dawn of multicellularity, and perhaps even to the dawn of oxygenic metabolism. Many tumor cells are hypoxic, and use glycolysis in favor of oxy-phosphorylation to metabolise. Whether this altered metabolism is a cause or consequence of cancer remains disputed. The way that healthy and cancer cells cope with reactive oxygen species (ROS) as well as the response of cells to radiation damage, is also integral to the understanding cancer. By bringing together experts from cancer biology, astrobiology and evolutionary biology, we hope to develop a new line of inquiry in cancer research.

Participant List
Workshop Agenda

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Mitochondria

Mitochondria are deeply implicated in cancer. They act like little powerhouses within cells that control the energy budget. They are also involved in apoptosis – programmed cell death. When cells become malignant, physical and chemical changes occur in mitochondria, and in the way mitochondria signal the rest of the cell and each other. An early observation of cancer, known as the Warburg effect, is that cancer cells prefer to generate their energy by an alternative chemical pathway known as glycolysis. This pathway is better adapted to low oxygen (hypoxic) conditions, and many solid tumors struggle to receive adequate oxygen. Glycolysis involves profound changes in mitochondria, so understanding the role of mitochondria in the context of the Warburg effect, hypoxia, and apoptosis evasion, could prove to be critical in controlling cancer.
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Electrical Properties of Cells

Most cell biology is dominated by focusing on biochemistry, but electromagnetic effects also play a crucial role in regulating cell behavior. Cells maintain an electrical potential difference of a few hundred millivolts across their membranes by actively pumping charged particles. A similar potential difference is maintained across mitochondrial membranes. Electric fields seem to play an organizing role in the transport of key molecules within the cell, and in regulating the traffic of molecules between the cytoplasm and the nucleus. Additional important electromagnetic effects are associated with microtubules. The secret electric life of cells remains largely unexplored territory, but it is clear that the progress of cells from healthy to malignant is accompanied by changes in their electromagnetic signatures, thus offering possible diagnostic opportunities, and even the possibility of controlling malignant progression by manipulating electric and magnetic parameters.
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Evolution, Development and Cancer: Connecting the Dots

Cancer is widespread among eukaryotes, and can be successfully tackled only by understanding its place in the story of life itself – especially the evolution of multi-cellularity. There is general agreement that the roots of cancer date back hundreds of millions of years. The ancient genes responsible for cancer are retained because they play a key role in embryo development. Normally these genes are subsequently silenced, but if they become re-awakened in the adult form, cancer is the result. The workshop is an ambitious attempt to connect the dots of evolutionary biology, developmental biology and cancer biology, bringing together three distinct communities in the search for hidden links that may form the basis of a radically new theory of cancer.
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Invasion: How cancer cells spread around the Body

Ninety per cent of cancer deaths occur when the neoplasm spreads beyond the primary tumor and invades other organs. This process, known as metastasis, normally signals a sharp deterioration in prognosis. The manner in which cancer cells migrate around the body remains an ill-understood process, but it is clearly a topic in which physical science is deeply involved. Normally cells quit the primary tumor and enter either the lymph system of the blood system (“intravasation”).
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Workshop exploring the links between chromatin configurations, gene expression, nuclear morphology and cancer.

The DNA in every human cell is about two metres long. Somehow it has to be packed into the tiny cell nucleus. Which presents nature with a problem: how can a thread so long be compacted without excessive tangling and knotting? Furthermore, in order for genes to be read, they need to be exposed to enzymes. That requires the DNA to be continually unraveled and re-packaged in an exquisitely precise and controlled manner. The first level of compaction is understood: the famous double-helix of DNA is wound around little reels made of proteins called histones, like beads on a string, forming what is referred to as chromatin. Many more levels of folding and wrapping produce the structures known as chromosomes, familiar from photographs of cell nuclei.
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Quantum Mechanics and Cancer Biology

The conjecture that quantum mechanics plays a key role in life dates back to the 1940s, and Erwin Schrödinger’s famous book “What is Life?” However, decades later, most scientists still assume that classical ball and stick models suffice in the realm of molecular biology. Recently there have been claims that quantum effects are essential in at least two biological processes – photosynthesis and bird navigation.
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Cellular Differentiation and Response to Stress: Modeling Cancer Initiation and Progression

Co-organizers: Thea Tlsty and Timothy Newman

The Sedona Workshop was held under the auspices of the Arizona State University Physical Sciences Oncology Center, and was the third in the series of focused workshops on different aspects of cancer. The core focus of this workshop was the differential response of tumor cells to environmental stress. This central issue was approached by three groups: i) experts in the cancer field, ranging from cell biologists to bioinformaticists to pathologists, ii) biologists and bioengineers with expertise in cell differentiation in the context of stem cells and developmental biology, and iii) a cadre of biological modelers, with backgrounds in physics, engineering, and mathematics.

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Understanding cancer in the context of evolutionary biology, how neoplasms evolve within the host organism, the nonlinear feedback between cancer cells and stroma, and how cancer behaves as a complex adaptive system. Emphasis will be on the application of dynamical systems theory, game theory, systems biology and related fields of inquiry to cancer and its progression to malignancy. The goal of the workshop is to determine how tumor growth, tissue invasion and metastasis might be understood and even controlled via these dynamical properties.

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