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Forbeck NL Spring 2003 WilliamREPORT Guy Forbeck Research Foundation VOLUME 18 / SPRING 2003 From The Chairman’s Desk SCIENTIFIC ADVISORY The most produc- Moritz Ziegler to address the topic of “The BOARD REPORT tive use of cancer New Biology of Enigmatic Neuroblastoma research dollars is the and Relevant Treatment Strategies.” Cell Death and reaction that you get An Appreciation Meeting was held in Edward A Frick when the William June to thank our many loyal Lake Cancer - an Guy Forbeck Cancer Research Geneva supporters. It was held at the Intimate Link. Foundation is discussed by leading scien- Lake Geneva CC with over 250 people in Several of our meet- tific researchers. This has been the attendance. Dr. John Kemshead from ings in Hilton Head emphasis of the Foundation since it was Baxter Labs, Dr. Bruce Chabner from have focused on cell founded in 1984. With over 1,000,000 Harvard and Dr. James Stewart from the death. This may people in the United States diagnosed University of Wisconsin participated in a seem rather strange John T. Kemshead, PhD with cancer each year, making cancer dol- stimulating and informative round table as cancer is the antithesis of this; it pri- lars more efficient is vital. discussion. At the meeting Bobby Smyth marily being thought of as resulting We are beginning to understand the caus- was presented with a Trustee Emeritus from uncontrolled cell growth. However, es of cancer and to initiate new methods Award for his many years of outstanding there are two reasons for our considered of prevention, diagnosis, and treatment. service to the Foundation. focus on this topic. The first is the hope The “war on cancer” is far from being There is a very special place in our that if we understand more about cell won, but some of the battles are begin- heart for Jim and Jennifer Buchanan, and control processes then we will under- ning to turn our way. their daughter Lindsay. Jim and Jennifer stand more about cancer. The second This past year’s forum addressed a started the Homefront Bike Tour and reason is that another way in which a key topic, “Cellular Senescence and raised over $345,000 for the Foundation. malignancy may arise is through cells Cancer”, and was chaired by Dr. Ronald Lindsay had neuroblastoma and in spite not understanding when to die. This DePinho from Dana Farber Cancer of this, was a tremendously positive young results in a mass or tumour as cells are Institute in Boston and Dr. Charles Sherr girl. Everything possible was done world- not being eliminated from the body at from St. Jude Children’s Research wide to stop this terrible disease but the right time. Hospital in Memphis. It was one of the Lindsay passed away on May 25th. Her The reasons why we do not suffer best sessions ever. The 2003 Forum topic courageous spirit will always inspire the from more cancers than we do, is in my will focus on “DNA Damage and Cancer Foundation and not a day goes by that I view down to control processes. Cells Susceptibility Syndromes” and will be don’t say a prayer for her. ...Continued on page 9 chaired by Dr. Alan D’Andrea from Dana This is the time of the year when we Farber Cancer Institute in Boston and ask for your renewed support to maintain From the Chairman’s Desk.................... 1 Prof. Dr. Jan Hoeijmakers from the the momentum that has been established. Scientific Advisory Board .................... 1 Erasmus University of Rotterdam It is through your generous help that con- Forum 2002: (Netherlands). tinuing progress will be made. Cellular Senescence and Cancer .............. 2 In 1999 the foundation established Thank you for your continuing assis- Awards and Grants................................ 6 the “Focus on the Future” program tance to the Foundation. Forums 2003 and 2004 ........................ 8 where grants are awarded to allow the Financial Report.................................... 9 recipients to hold meetings similar in con- Benefactor List .................................... 10 tent and format to the very successful Objectives .......................................... 12 Board of Trustees & annual Hilton Head Forums. The 2003 Edward R. Frick In This Issue... Scientific Advisory Board .............. 12 Focus grant was been awarded to Dr. Chairman, Board of Trustees th 2002 Forbeck Forum: XVIII Annual Forum November 7–9, 2002 Hilton Head Island, South Carolina “Each day, I Subject: Cellular Senescence and Cancer encounter patients and I: Telomere Biology in Human Cell Systems their families whose lives II: Tumor Suppressors / Senescence Pathways are touched by cancer. III: Modeling Cancer & Cancer Genomes It is heartening to see IV: Models / Methods to Probe Senescence such dedication on your part to eliminate this Chairmen modern black plague.” Ronald DePinho, MD Harvard Medical School Boston, MA Charles Sherr, MD, PhD St Jude Children’s Research Hospital Memphis, TN Ron DePinho, MD Ron DePinho, MD Participants Judith Campisi, PhD Lawrence Berkeley National Laboratory Berkeley, CA Titia de Lange, PhD Rockefeller University New York, NY “I thought that the Steven Elledge, PhD Baylor College of Medicine Houston, TX meeting was a great Gerard Evan, PhD University of California San Francisco, CA success. I enjoyed William Hahn, MD Harvard Medical School Boston, MA everything — the sci- ence and the venue and Gregory Hannon Cold Spring Harbor Laboratory Cold Spring Harbor, NY the socializing.” Jacqueline A. Lees MIT Center for Cancer Research Cambridge, MA Scott Lowe, PhD Cold Spring Harbor Laboratory Cold Spring Harbor, NY Charles Sherr, MD, PhD Jerry W. Shay, PhD UT Southwestern Medical Center Dallas, TX Maarten van Lohuizen the Netherlands Cancer Institute Amsterdam, Netherlands Karen H. Vousden, PhD National Cancer Institute Frederick, MD Charles Sherr, MD, PhD 2002by Ronald A. ConferenceDePinho, M.D. & Charles J. Report Sherr, M.D. Ph.D. This exciting and highly productive pathways influence the biological impact a permissive microenvironment for Forum focused on cellular senescence – a of oncogenic lesions such as Myc and epithelial carcinogenesis. Such senescent biological response governed by known can we forge a link to the core cell cycle microenvironment cells secrete proteases cancer-relevant pathways and thought to machinery? A discussion of these issues among other factors that have been be integral to the suppression of cancer generated more questions than answers linked to tumor progression. and the response to anti-cancer agents. and the level of discussion was so robust Dr. Titia de Lange of the Investigators from diverse areas discussed that most speakers found it challenging Rockefeller University discussed how the cellular senescence mechanism from to get past the first few slides of their abnormal telomere structure activates a the molecular, cellular and organismal talk. senescent response in mouse and human perspectives. Numerous outstanding Dr. Judith Campisi of Lawrence cells. She emphasized that, although questions were discussed including: Berkeley National Laboratory focused on there is general agreement on the involve- Does senescence represent an effective the issue of the cellular senescence is an ment of p53 in the senescence signaling mammalian tumor suppressor mecha- example of evolutionary antagonistic pathway, the data are less clear on the role nism on one hand yet drives the age- pleiotropy and presented evidence that of p16. Furthermore, the telomere dam- related pathologies on the other? Are cellular senescence in cultured cells is age signaling pathway appears to be dif- there species-specific differences in mice driven by a ferent in human and mouse cells as and humans or does this relate to exper- process linked to “This was one of the reflected in the response of these cultured imental design? What role do telomeres accumulated most stimulating and cells to alterations in telomere structure plays in suppressing or fueling chromo- oxidative stress. enjoyable meetings I’ve brought about by the expression of aber- ever attended. Many somal instability and how does this She also reviewed good ideas (and some rant telomere binding proteins. influence the initiation and progress of the evidence that collaborations) have Dr. Ron DePinho of the Dana- cancer in the organism? What are the strongly suggests already come out of it, Farber Cancer Institute and Harvard nature of the signals emanating from the that senescent and more will perco- Medical School presented his work on telomere and how is this signal mediated cells accumulate late through in the engineered mice harboring defective by damage signaling pathways in normal in normal tissues, future, I am sure.” tumor suppressor pathways and critically and neoplastic cells? How is telomerase and that these Judith Campisi, PhD shortened telomeres and how such alter- regulated? How do cellular senescence cells may provide ations impact on processing of aging and 2 cancer. He presented data showing that genes he recently identified in genetic protein in ß cells together with switch- advancing age, telomere attrition, and screens that repress telomerase expression able c-Myc. In this case, activation of c- accompanying genomic instability coop- in normal cells. Many of these were Myc triggers rapid, progressive and inex- erate to compromise the overall health linked to tumor suppressor pathways, orable ß cell neoplasia that is immediate- and well-being of mammals on the level furthering the link between telomerase ly accompanied by profound angiogene- of tissue stem cells. The telomerase and cancer. sis and local invasion. Similar oncogenic knockout mouse has provided a model to Dr. Gerard Evan of University of results are obtained upon activation of c- dissect the complex role of telomeres in California presented his elegant mouse Myc in ß cells lacking the tumor sup- cancer pathogenesis. Cancer, particular- models of cancer designed to understand pressors p19ARF or p53, although each ly epithelial carcinomas, is among the the immense complexity of the tumor type of anti-apoptotic lesion has its own most common aspects of aging in phenotype and the underlying genotype.
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