Emerging Strategies to Overcome Heterogeneous Resistance Mechanisms

Forum Chairs

Joan
Brugge
,
PhD
Harvard Medical School
Kris Cameron
Wood
,
PhD
Duke University

Forum Description

Drug resistance limits the depth and duration of clinical responses to most anticancer therapies, including targeted therapies. This fact has motivated intense efforts in recent years to define the mechanisms of resistance to commonly used anticancer drugs based on the hope that by doing so, it will be possible to design new therapies that block these mechanisms and thereby circumvent resistance. In fact, the 2013 Forbeck Forum on Resistance Mechanisms, led by Joan Brugge, Ph.D. and Jeff Engelman, M.D., Ph.D., explored precisely this topic. Unfortunately, we now know that many diverse resistance mechanisms can exist for each drug, and these mechanisms often co-occur within individual patients. As a result, efforts to improve therapeutic responses by blocking individual resistance mechanisms have largely failed, while efforts to block combinations of resistance mechanisms have been limited by toxicities.

In light of this challenge, emerging studies in the field are seeking to identify creative and fundamentally new strategies to circumvent resistance. These strategies include identifying common downstream signaling nodes shared by many or all major resistance mechanisms; profiling resistant cells to identify “collateral sensitivities” – vulnerabilities caused by evolutionary trade-offs made by cancer cells along the path to resistance; defining drug combinations with non-overlapping resistance landscapes, and exploring the possibility of individually targeting discrete subclones. Already these studies have yielded compelling results. However, they have largely been performed in isolation from one another. Now is, therefore, an opportune time to gather experts in the field working on the problem of heterogeneous resistance to discuss and critically examine these emerging strategies with the goal of identifying key areas for focus and collaboration.

Forum Summary

Drug resistance limits the depth and duration of clinical responses to most anticancer therapies, including targeted therapies. This fact has motivated intense efforts in recent years to define the mechanisms of resistance to commonly used anticancer drugs based on the hope that by doing so, it will be possible to design new therapies that block these mechanisms and thereby circumvent resistance. In fact, the 2013 Forbeck Forum on Resistance Mechanisms, led by Joan Brugge, Ph.D. and Jeff Engelman, M.D., Ph.D. from Harvard Medical School, explored precisely this topic. Unfortunately, we now know that many diverse resistance mechanisms can exist for each drug, and these mechanisms often co-occur within individual patients. As a result, efforts to improve therapeutic responses by blocking individual resistance mechanisms have largely failed, while efforts to block combinations of resistance mechanisms have been limited by toxicities.

In light of this challenge, emerging studies in the field are seeking to identify creative and fundamentally new strategies to more fully understand, and eventually circumvent, resistance evolution. At this meeting, held October 28-31 in Denver, CO, participants discussed cutting-edge insights and findings central to these areas. For example, in one area, investigators described high resolution studies defining the genetic heterogeneity and clonal evolutionary patterns observed in cancer patients with advanced disease. In another set of presentations, we learned about new tumor models that more accurately reflect the biological states of tumors in vivo, including those progressing on therapy. A third set of talks touched on ways in which principles of anti-tumor immunity can be advanced to make more patients responsive to powerful immunotherapies. In a fourth area, investigators described creative new approaches aimed at delaying, circumventing, or reversing resistance to high priority therapeutics. Finally, the meeting concluded with a series of bedside-to-bench discussions focusing on cutting-edge strategies to understand how tumor cells adapt to therapy, work which is already leading to pioneering new clinical trial approaches.

This Forbeck Forum provided a unique opportunity for investigators from around the world who are working on the above concepts largely in isolation to gather, discuss, and critically examine emerging concepts within the field of resistance evolution. The meeting generated tremendous enthusiasm from its attendees, who concluded the meeting with discussions of new governing concepts in the field, potential collaborative projects, ideas for sharing the concepts described in the meeting with the general scientific community through publications, and aspirations for a relatively near term follow up meeting.

Venue & Travel Information

Hilton Denver Inverness

200 Inverness Drive West
Englewood, CO 80112

hilton.com
303-799-5800

Travel Forms

Travel forms are due 30 days prior to the start of the meeting to allow enough time to plan transportation.

Denver International Airport (DIA) is approximately 30 minutes from the meeting location.

  • Arrivals - Thursday around 1 PM, 3 PM and 5 PM
  • Departures - Sunday around 10 AM and 12 PM
TRAVEL FORMS DUE:
September 28, 2021
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:
September 28, 2021
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

Saurav
Bandyopadhyay
,
PhD
University of California, San Francisco
Alberto
Bardelli
,
PhD
University of Torino
Trever
Bivona
,
MD, PhD
University of California, San Francisco
Christina
Curtis
,
PhD, MSc
Stanford University
Christine
Lovly
,
MD, PhD
Vanderbilt University
Ira
Mellman
,
PhD
Genetech
Gordon
Mills
,
MD, PhD
Oregon Health and Science University
Nick
Navin
,
PhD
MD Anderson
Kornelia
Polyak
,
MD, PhD
Dana Farber Cancer Institute
Sydney
Shaffer
,
MD, PhD
University of Pennsylvania
Charles
Swanton
,
MBPhD, FRCP, FMedSci
The Francis Crick Institute
Kris Cameron
Wood
,
PhD
Duke University

Forum Scholars

Kirsten Bryant, PhD
University of North Carolina
Cihangir Duy, PhD
Weill Cornell Medical
Peter Winter, PhD
Massachusetts Institute of Technology