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Archive - Oct 28, 2015

[TECHNOLOGY USED; UPDATE 10-31] Cancer-Derived Exosomes with Specific Integrin “Zip-Code” Signatures Target & Prime Specific Organs for Later Metastastis; New Work Supports Century-Old “Soil & Seed” Hypothesis for Metastatic Organotropism

[SEE LAST PARAGRAPH TO VIEW UPDATE ON THE TECHNOLOGY USED IN THIS LANDMARK STUDY] It's been a longstanding mystery — why certain types of cancers spread to particular organs in the body. Now, investigators from Weill Cornell Medicine, together with an international team of collaborators, have discovered precisely how this happens, supporting a century-old hypothesis known as the “seed and soil” theory of metastasis. The culprit? Protein signatures on the membranes of small, sub-cellular, tumor-secreted vesicles (exosomes) containing the blueprint that drives cancers to distant organs. These signatures could offer doctors a powerful new way to detect whether a patient's tumor will metastasize and to where, providing critical insights into the estimated 1.6 million new cancer cases diagnosed every year. Ninety percent of all cancer-related deaths are related to metastasis. In the new study, published online on October 28, 2015 in Nature, scientists investigated the role of cancer-derived exosomes, comprised of tumor-derived proteins, in preparing a microenvironment fertile for cancer metastasis. Working with exosomes derived from multiple cancers, the scientists discovered that the proteins exosomes carry act as "ZIP codes" that direct exosomes to distinct organs, where they lay the molecular groundwork for metastases to form. The Nature article is titled “Tumor Exosome Integrins Determine Determine Organotroppic Metastasis.” "Our research offers a new approach to identifying patients who are likely to develop metastatic disease," says senior author Dr. David Lyden, the Stavros S. Niarchos Professor in Pediatric Cardiology and a Professor of Pediatrics and of Cell and Developmental Biology at Weill Cornell Medicine in New York City.

Personalized Medicine Analysis Identifies Novel Mutation That Gives PTEN Protein New Tumor-Promoting Ability, While Preserving Its Normal Tumor Suppressor Activity

In a “personalized medicine” study that presents a framework for interpreting a single patient’s genome, collaborating scientists at the Stanford University School of Medicine, UCSF, Gladstone Institutes, and Phillipps-Universitat Marburg, have identified a novel point mutation in the PTEN tumor suppressor gene that allows the altered PTEN protein product (image shows structure of normal PTEN protein) to retain its known suppressor function, while gaining new tumor-promoting activities. In addition, the scientists have demonstrated that the tumor-promoting activities of the mutated PTEN protein can be substantially mitigated by chemical inhibitors of PI3K (phosphoinositide 3-kinase). The researchers believe that their work suggests a new role for PTEN, as well as other tumor suppressors, in cancer formation, and also reveals the potential wealth of biological information currently underexploited by the lack of systematic approaches for cancer genome interpretation services. The authors believe that their results “demonstrate a new dysfunction paradigm for PTEN cancer biology and suggest a potential framework for the translation of genomic data into actionable clinical strategies for targeted patient therapy.” The new PTEN mutation and the systematic analyses that led to its discovery and characterization are described in an online open-access article published on October 26, 2015 in PNAS.