Molecular Origins of Pediatric Embryonal Malignancies
Forum Description
Sessions:
- Cancer as a Genetic Disorder
- Biologic Basis of Embryonal Malignancies: Disordered Differentiation
- Somatic Mutation as an Oncologic Mechanism
- Molecular Mechanisms of Oncologic Import
A group of internationally respected investigators convened on Hilton Head Island from 15 to 17 November, 1990 to focus on the Molecular Origins of Pediatric Embryonal Malignancies, the topic of the VIth Annual William Guy Forbeck Research Foundation “Think Tank Forum.” The goal of this unique forum was twofold – to identify the most recent advances in our understanding of the genetic basis of pediatric malignancies and to evaluate findings that might offer new opportunities for the development of new diagnostic or therapeutic targets.
During the past decade, novel approaches to cancer research have emerged that are providing important insights into the molecules involved in the conversion of a normal cell to a malignant one. Particularly important have been the dramatic advances in cell biology and recombinant DNA technology that have focused attention on cancer as a genetic disorder. The identification of specific genetic alterations that seem to be related intimately to malignancy has been of pivotal importance and has opened new lines of investigation, elucidating the biochemical pathways that mediate the development of cancer and its clinical features. There is now widespread recognition that the biologic alterations indicative of malignancy are closely related to events integral to the formation of complex organisms. Coordinated growth regulation, differentiation, the development of complex tissues, and cell migration are now under intense scrutiny and cancer is emerging as a disorder of these normal physiologic events. Within this framework, it should be possible to reconcile many of the diverse laboratory and clinical observations that have led to cancer’s being considered among the most enigmatic of diseases.
Discussions during this forum provided an opportunity for outstanding investigators working on different pediatric tumors and different cellular mechanisms of growth control to interact and share both their most recent findings as well as details of their experimental approach. Without doubt, there was a vigorous and highly productive exchange of scientific ideas.
Forum Summary
Pediatric embryonal tumors were the first malignancies in which a response to chemotherapy was recognized and they have since been important clinical models in developing many principles of cancer treatment. The molecular origins of embryonal tumors were the focus on the 1990 Forbeck Forum, where laboratory researchers and clinical oncologists met to exchange ideas about the regulation of cell differentiation and growth and its disruption on childhood cancer.
The forum first addressed childhood cancer as a genetic disorder. A chain of sequential genetic events may lead to the development of embryonal tumors and contribute to their highly malignant behavior. Wilms tumor, for example, may develop in a child whose kidneys failed to differentiate and mature normally during embryonic development. Neuroblastoma and retinoblastoma may develop similarly. Within this context, the forum then focused on molecular studies, emphasizing the role of tumor suppressor genes in the development of childhood tumors. Malignant (cancerous) changes in cells at the molecular level are often associated with the loss of genetic material, which appears to be a sensitive indictor of the site of tumor suppressor genes on a chromosome, the structure in the cell’s nucleus that carries the genes. The loss of genetic material from tumor cell chromosomes appears to have great importance in the development of cancer.
Childhood tumors seem to be genetically distinct from the corresponding tumors in adults. Possible one third of all childhood embryonal brain tumors have an alteration and loss of DNA sequences from chromosome 17. This particular structural anomaly has been seen in only one of over 100 adult gliomas studies. In adult gliomas that have lost chromosome 17 DNA sequences the loss may be related to the abnormalities of the p53 gene, but preliminary studies of p53 in several pediatric gliomas did not show the mutations in this gene. Rather, it seems that a different gene on the short arm of chromosome 17 distal to p53 might be involved.
The functional role of proteins encoded by tumor suppressor genes was discussed extensively. At least three types of such genes have been defined: 1. Genes that control the growth rate of life span of cells under experimental conditions; 2. Genes that control tumorigenic potential of individual cells; 3. Genes that regulate normal cellular differentiation. Provocative biochemical studies of growth suppression by tumor suppressor genes have shown molecular interactions that suggest a link between those genes and cell cycle regulatory mechanisms, but the significance of those interactions is still unclear. Other genes are known to contribute to tumor development by stimulating cell growth. Among these oncogenes, mos is one of the best understood. It has been shown for the first time that the normal counterpart of the mos gene functions during a critical phase of the cell cycle, suggesting that the transforming ability of mos stem from the inappropriate activation of cell cycle division at a time when cellular growth should be arrested.
In other work, research findings emphasize that successful treatment depends not only on the choice of therapy, but also on the biologic characteristics of the tumor and, presumably, the patient. While most of the body’s natural defenses against cancer cells are not well understood, it appears that some naturally occurring substances either can modify the biologic behavior of tumor cells or are tumoricidal. In planned clinical studies, tumor infiltrating cells (TILs) are genetically altered in the laboratory by the addition of a gene encoding necrosis factor (TNF) to yield TNF-producing cells that can specifically target tumor cells. These cells will then be used in treating cancer patients to produce high local concentrations of TNF. This new site-directed therapy should permit clinicians to lower severely toxic systemically administered doses of TNF.
The different but distinctly related lines of investigation discussed during the 1990 Forbeck Forum on Molecular Origins of Pediatric Embryonal Tumors provided important insights into the molecular events that initiate and mediate the oncogenic process. It appears that pediatric embryonal tumors again will serve as important models in designing novel approaches to cancer treatment.
Quotes from Participants
“It was an exciting few days that I feel was unusually successful in bringing together leaders from different areas of the cancer field and encouraging their interaction. I admire the Foundation’s dedication to research in the basic mechanisms of childhood cancers, and I strongly encourage you to continue on your present course. There is clearly a gap between the majority of basic scientists and clinicians. An open Forum such as yours, which includes these two groups, is the only way as I see it to bring them together in a meaningful way. -- Eric N. Olson, Ph.D., MD Anderson Cancer Center, Houston, TX
“The Forbeck Forum has become well recognized as an important and vibrant contribution to our search for improving the lives of children afflicted by cancer.” -- Philip A. Pizzo, MD, National Cancer Institute, Bethesda, MD
“… the format was exceptional in promoting communication and exchange.” -- June Lee Biedler, Ph.D., Memorial Sloan-Kettering, New York, NY
“There already is some tangible benefit to my program … as I have developed at least two collaborations on the problems that we are addressing in childhood tumorigenesis that might otherwise not have occurred … the format is unique … it is this approach to scientific exchange that makes information transfer and idea generation take place at a more rapid pace.” -- Beverly S. Emanuel, Ph.D., Children’s Hospital of Philadelphia, PA
“For me the meeting was very timely, since experimentally and conceptually we are changing our directions … I think the contacts I got during these days will be of great importance in the future. A few collaborations have already been settled.” -- Sven Pahlman, Ph.D., University of Uppsala, Sweden
“I feel that this was one of the best meetings I ever attended. All facets of the meeting seemed to foster exactly the type of interactions that are most lacking in assemblies of scientists. I wish there were more opportunities for symposia of this nature.” -- Bernard E. Weissman, MD, University of North Carolina, Chapel Hill
Venue & Travel Information
Travel Policy
Please familiarize yourself with our policies and procedures for travel. We truly appreciate you taking the time to participate in this forum. As you make your plans, please remember that we are a nonprofit organization dependent on donations and volunteers. We do NOT pay for upgrades, change fees, incurred costs resulting from a flight change, transportation to or from your local (home side) airport, meals or other incidentals.
- Travel Confirmation will be sent out within 1 week of the forum. This will include a hotel confirmation number, if there is one, and airport transfer details. We have to wait until we receive almost everyone’s travel to book airport transfer. Due to frequent airline changes, we wait until the week of the forum to send this out.
- Airport transfer is provided by Foundation staff, volunteers or arranged shuttle at specific times. If you opt to utilize Foundation airport transportation on your travel form, please be patient in receiving this information. We will send it to the week of the forum.
- Speaker agenda is not sent out prior to the forum. It will be provided upon arrival in the forum packet. We do not tell people when they are speaking because we expect everyone to attend all sessions. Sessions are all day Friday and Saturday.
- REMINDER: We do not reimburse for home side airport transfer or incidentals while traveling. We will not honor miscellaneous receipts sent for these expenses.
- Spouses are welcome to come with you at their own cost but are not allowed to attend the forum. Please no children.
What the Foundation Pays
Accommodations and meals are provided by the foundation during the forum. Airfare will be covered only if booked in accordance with our policy and only up to the amount in which you were approved for. The Foundation will also cover airport transportation on the forum side at the designated shuttle times. You can select not to utilize Foundation arranged transportation at your own expense when completing the travel form. Once your travel form is received your accommodations and airport transfer will be confirmed. Please let us know of any food allergies or other information we should be aware of on the travel forms.
- Note we do not cover upgrades, changes, late bookings, etc.
- Flights must be booked at least 30 days prior to the forum to confirm your accommodations and airport transfer.
- As a nonprofit we utilize volunteers and other methods to maximize our efforts (or our donor support) when making accommodations and arranging ground transportation. Ground transportation will be provided upon your arrival either by a foundation volunteer or arranged shuttle. You will be provided airport transportation information the week of the forum. We do not reimburse for home side airport transfer or incidentals while traveling.
Abstracts
Abstracts are due 30 days prior to the start of the meeting to allow enough time to prepare the meeting book.
The abstracts should be only one or two paragraphs outlining the theme of your presentation and should reflect the objective and spirit of the meeting (see above). Abstracts will be circulated about one week before the meeting. The meeting organizer will start requesting them a month before the meeting.
Forum Structure
The structure of the forum has been developed over years of experience.
- Participants have approximately 45 minutes, depending on the number of participants, for their presentation and discussion. The presentation is meant as a conversation start and should last about twenty minutes briefly covering background information and areas that are new or need further input. This should be structured in such a way as to lead to a lively discussion. Participants are encouraged to interrupt to ask questions or start discussions.
- A MAXIMUM of 2 slide equivalents per presentation is allowed (Power point slides should not contain more than one graph or gel per slide and no more than 5 bullet points to stress the points being made by the presenter.) We appreciate cooperation with the spirit of this guideline. Handouts are welcome but should be distributed before sessions.
- Everyone is expected to actively participate in every session and discussions.
- The time spent at the forum is relatively short, so please be familiar with papers received prior to arrival.
- It is very important that you commit to all sessions of the 2 days of the forum.
Forbeck Scholars Participation
Scholars are selected for each Forbeck Forum. These are outstanding junior clinical or post-doctoral fellows selected based on the quality and relevance of science.
- Scholars present for 30-45 minutes, depending on the number of participants
- The same presentation rules apply for scholars
- After the Forum you are selected to attend, you will attend three years of Scholar Retreats held in Lake Geneva, WI. If you attend a Fall Forum, you will attend the Spring Retreat. If you attend a Spring Forum you will attend a Fall Retreat.
- Scholars are selected by the Foundation Scientific Advisory Board and peer reviewers selected from past Forbeck Scholars.
General Program
The outline below illustrates a typical program schedule. You will receive a complete schedule, including speaking times, the Thursday the forum starts.
Frequently Asked Questions
Below are some of our most Frequently Asked Questions. If you have something new to ask, please feel free to contact us.
- Travel Confirmation will be sent out within 1 week of the forum. This will include a hotel confirmation number, if there is one, and airport transfer details. We have to wait until we receive almost everyone’s travel to book airport transfer. Due to frequent airline changes, we wait until the week of the meeting to send this out.
- Airport transfer is provided by Foundation staff, volunteers or arranged shuttle at specific times. If you opt to utilize Foundation airport transportation on your travel form, please be patient in receiving this information. We will send it to the week of the forum.
- Speaker agenda is not sent out prior to the meeting. It will be provided upon arrival in the meeting packet. We do not tell people when they are speaking because we expect everyone to attend all sessions. Sessions are all day.
- Frequently airport transfer is provided by volunteers. Please be patient on receiving this information. Airport transfer will be sent out prior to arrival.
- REMINDER: We do not reimburse for home side airport transfer or incidentals while traveling. We will not honor miscellaneous receipts sent for these expenses.