Growth Factors

Forum Chairs

John
Mendelsohn
,
MD
Memorial Sloan Kettering Cancer Center

Forum Description

Sessions:

  1. Receptors and Growth Factors
  2. Signal Transduction I
  3. Signal Transduction II
  4. Human Cancer

"Dr. Mendelsohn planned the Forum on “Growth Factors” with emphasis on those that mediate signal transduction through protein tyrosine kinases. His hopes were for a “truly creative think tank.”In July 1996, Mendelsohn assumed the presidency of M. D. Anderson, becoming only the third full-time president of the Houston-based institution.

Forum Summary

This year’s topic was growth factors. The central theme of the meeting was the mechanisms by which growth factors regulate cells through signal transduction pathways.

During the past two decades, it has been learned that cells (including most cancer cells) cannot grow in a purely autonomous fashion. Instead, their capacity to grow and multiply is regulated by growth factors. These are small polypeptide molecules which bind to highly specific receptors on the cell surface, the way a key fits into a lock. In the presence of appropriate growth factors, cells activate the biochemical pathways which enable them to replicate DNA and undergo mitotic cell division."

"Research on the nature of the biochemical steps that can carry a signal from receptors in the cell surface membrane to the genes that control cell function has opened up an exciting area of investigation with tremendous clinical potential. A series of biochemical steps are involved in this transfer of information, creating what is known as signal transduction pathways. In parallel with discovering the individual ‘players’ in these pathways, there has been a great deal of activity attempting to develop specific pharmacologic agents that can block the various steps, thereby regulating cancer cell proliferation.

The assembled group of investigators represented a wide variety of disciplines. Each of the presentations stimulated questions and discussion, forcing us to convene far past the planned hours.

Entry into signal transduction is initiated by the biding of a growth factor to its receptor. Rik Derynck presented information suggesting the transforming growth factor acts both as a stimulator of the epidermal growth factor and as a receptor molecule in its own right. This raised the interesting possibility that a molecule can serve that cells use to regulate activities such as cell growth. Growth factor receptors in cell surface membranes contain an intrinsic enzyme activity called a tyrosine kinase, which is able to phosphorylate proteins on their tyrosine residues. Many other kinases are found inside the cell, and are activated as a secondary step when growth factors bind to receptors on the cell surface. Dr. Sarah Parsons described experiments which explain the mechanism of activating the best understood of these kinases, the c-src tyrosine kinase. Dr. Joseph Bolen expanded on this theme, outlining a long list of intracellular tyrosine kinases that seem to have developed specialized activities in particular cells for example in lymphocytes. There has been a great deal of progress defining the structures of these kinases and the mechanisms by which they act in the signal transduction pathway.

One of the main targets of the proteins that are phosphorylated by kinases is an important oncoprotein known as ras. Dr. Neal Rosen presented interesting studies with colon carcinoma lines which demonstrate the way that ras interdigitates with other signaling molecules. Screening tests have demonstrated that ras is abnormal because of mutations in about half of the colon cancer cells examined. Pathways have been identified which could accomplish similar biochemical consequences in situations where the ras protein is normal. Dr. John Hancock presented exciting information showing the capacity of new drugs to block the function of ras. Clinical trials are planned with these inhibitory agents.

Other potential therapeutic approaches were also considered. Dr. David Heimbrock described compounds which act on the Rb protein, another regulator of cell cycle division, and other drugs which block an important regulatory kinase known as PI-3 kinase. Dr. Ed Sausville presented possible therapeutic attacks at a number of levels of the signal transduction pathway. The herbimycins and small synthetic chemicals known as tyrphostins can directly block the tyrosine kinases associated with receptors or free in the cell. Other molecules such as flavines and aphidocholine block steps in the growth cycle of cells which also may be exploitable in the treatment of cancer.

In these presentations, there was emphasis on the phosphorylation of proteins as key regulatory steps. Drs. Benjamin Neel and Nicholas Tonks provided important evidence that phosphorylation in itself is regulated, by enzymes known as phosphatases. These phosphatases can directly counteract the activity of kineses, by dephosphorylating proteins that have been activated by kinases. The fine tuning of the “yin-yang” balance in phosphorylation is only beginning to be understood, but again, provides a focus for pharmacologic intervention in the future.

At the end of the meeting there was a great deal of enthusiasm about the knowledge that had developed, explaining the mechanisms by which the binding of growth factors to receptors on the cell surface can activate signaling pathways that regulate cell proliferation. These discoveries, in turn, provide many leads towards new chemical agents with potential therapeutic efficacy, and some of these have already moved into clinical trials. This is yet another example of how fundamental scientific research is leading to new advances in health care, specifically in the area of cancer treatment.

Quotes from Participants
“The Forum provided me with the opportunity to talk in an environment which was especially conducive to open and frank discussion. I wouldn’t have thought it possible that a 5-slide talk was 2 slides too many … We are looking forward to several new collaborations …”. -- David C. Heimbrook, Ph.D., Merck Research Laboratories, West Point, PA

“It was a very productive meeting for me in that my views were expanded and I was able to meet so many of the top researchers in the field face-to-face.” -- Mark S. Marshall, Ph.D., Indiana University Medical Center, Indianapolis, IN

“The format of the meeting is incredibly conducive to exchange of ideas that will allow the field to advance more rapidly. I only wish all meetings could be like this one! …it made me think about different approaches that I might use in my own area. It was particularly enjoyable to see the participants freely hypothesize about why things happen the way they do …”. -- Daniel S. Wechsler, MD, Ph.D., The Johns Hopkins Oncology Center, Baltimore, MD

“It is indeed difficult to quantitate an effort to facilitate meaningful one-on-one communication between scientists. However, it may well be one of the most important and noble functions an organization can serve. All of us are usually too busy with our work to have extended conversations with our colleagues who we rarely see in person. Providing a diverse group of scientists with such an opportunity is clearly beneficial. In my case, having time to talk with members of the panel that met in 1993 was important in bringing to focus several issues.” -- Joseph Bolen, Ph.D., Bristol-Myers Squibb, Princeton, NH

Venue & Travel Information

Hilton Head Island

Travel Forms

TRAVEL FORMS DUE:
October 4, 1993
submit travel form

Travel Policy

Please familiarize yourself with our policies and procedures for travel. We truly appreciate you taking the time to participate in this meeting. 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 meeting. 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 meeting.
  • 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 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 meeting. Please no children.

What the Foundation Pays

Accommodations and meals are provided by the foundation during the meeting. Airfare will be covered only if booked through our travel agent. The Foundation will also cover airport transportation on the meeting 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.

  • If you would like your airfare covered by the Foundation, you must book with our travel agent. Note we do not cover upgrades, changes, late bookings, etc.
  • Flights must be booked at least 30 days prior to the meeting 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 meeting. 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.

abstracts DUE:
October 4, 1993
submit abstract

Meeting Structure

The meeting structure 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 5 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 meeting is relatively short, so please be familiar with papers received prior to the meeting.
  • It is very important that you commit to all sessions of the 2 days of meetings.

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 meeting starts.

Arrival Day
1:00 PM Arrivals
6:00 PM Cocktails (opt'l)
7:00 PM Dinner
Meeting Day 1
7:00 AM Breakfast
8:00 AM Scientific Sessions
12:00 PM Lunch
1:30 PM Scientific Sessions
6:00 PM Cocktails & Dinner
Meeting Day 2
7:00 AM Breakfast
8:00 AM Scientific Sessions
12:00 PM Lunch
1:30 PM Scientific Sessions
6:00 PM Cocktails & Dinner
Departure Day
7:00 AM Breakfast
8:00 AM Departures

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 meeting. 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 meeting.
  • 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 Friday and Saturday.
  • 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.

Forum Participants

Nicholas
Tonks
,
PhD
Cold Spring Harbor Laboratory
Yosef
Yarden
,
PhD
Weizmann Institute of Science

Forum Scholars

Daniel Wechsler, MD, PhD
Emory University