Cancer Biology and Autism

An important new paradigm in autism research is that better understanding of its causes might be found by studying the biochemical circuits that control synaptic plasticity. Knowledge about the intracellular pathways that govern the response of a cell to external stimuli has come from efforts to understand how cancer develops, since many oncogenes code for proteins that participate in these signaling cascades. Mutations that give rise to cancer are often found in genes that code for kinases, phosphatases, and tumor suppressors. It is a remarkable development of twentieth century science that all eukaryotic cells, from all species and from all organs and physiological systems within a species, share a common set of signaling elements.  The signals ultimately control the metabolism (energy), transcriptional status (demand for more proteins), or the motility (growth) of the cells.

Neurons are highly specialized and differentiated cells with unusual electrical and chemical mechanisms for communicating information across incredibly complex networks. The dominant theme in neuroscience is that learning and memory are intimately connected with changes in points of contact between neurons, the synapses, which undergo up and down variations in ‘synaptic strength’ depending on what use is made of a particular synapse in a neuronal net. Dendritic spines, micron-sized compartments, that constitute the receiving end of a synaptic transmission are dynamic structures that change their shapes and biochemical composition in response to neurotransmitter release into the synaptic cleft. The resulting flows of calcium into the spine, and a cascade of phosphorylation, bring about polymerization of actin which underlies the changes in size and shape necessary for an increase in synaptic strength.

This suggests an important connection between cancer biology and autism: genetic ‘hits’ to biochemical circuits controlling metabolism, transcription, and motility may be a fundamental cause. Recent experiments (conducted at MIT) on genetically altered mice confirm this insight. If confirmed in humans, this hypothesis would imply that some forms of autism are chronic and potentially treatable by drugs now under development for cancer, diabetes and other disorders.  A Boston Club held on December 6, 2007 on ‘Cancer Biology & Autism’ focused on exploring this exciting theme.

Matthew Anderson, MD, Ph.D., Beth Israel Deaconess Medical Center

Molecular Windows into Brain Size and Language Development
Matthias Groszer, MD, University of Oxford

Dirk Iglehart, MD, Brigham and Women’s Hospital

Tal Kenet, Ph.D., Massachusetts General Hospital

A Possible Role for the p53-IGF-1-mTOR Pathways in the Origins of Autism
Arnold Levine, Ph.D., Institute for Advanced Study

The Microfilament System in Health and Disease
Uno Lindberg, Ph.D., Karolinska Institute

Damon Page, Ph.D., Massachusetts Institute of Technology

Richard Sidman, MD, Beth Israel Deaconess Medical Center

Role of IGF1 Signaling in Brain Development, Plasticity and Autism
Mriganka Sur, Ph.D., Massachusetts Institute of Technology

Marc Vidal, Ph.D., Dana Farber Cancer Institute

Noncoding RNAs: Possible Involvement in Fragile X Syndrome and Autism
Claes Wahlestedt, MD, Ph.D., Scripps Research Institute

2007

The Nancy Lurie Marks Family Foundation, Wellesley, MA