Non-genetic Drug Tolerance Mechanisms

Forum Chairs

Shruti
Bhatt
,
PhD
Dana-Farber Cancer Institute
Anthony G.
Letai
,
MD, PhD
Dana-Farber Cancer Institute
Yaara
Oren
,
Tel Aviv University

Forum Description

Despite a favorable initial response to therapy, a third of cancer patients will develop recurrent disease and succumb within five years of diagnosis. It is widely accepted that relapse can be driven by genetic mutations that were either pre-existing or arose de-novo during drug treatment. Over the last decade a rare subpopulation of cells, termed cancer persister cells, have been identified as orthogonal drivers of treatment failure. Unlike resistant cells that harbor a genetic alteration that enables them to survive and expand in the presence of a drug, persister cells are transiently drug-tolerant cells that can survive exposure to therapy through reversible, non-mutational mechanisms. The nascent field of cancer persistence has expanded rapidly since the first cancer persister system was reported 12 years ago. Initially described in the context of targeted therapy, drug-tolerant cancer cells have since been implicated in disease recurrence in multiple cancer models and in response to a diverse array of treatments.

This Forbeck forum will provide a unique opportunity for investigators from around the world who are working on this newly emerging field in cancer to gather, discuss, and critically examine emerging concepts in the field of cancer persisters. We will start with understanding molecular mechanisms of cancer persistence and will continue with discovering therapeutic targets of persistent cells, deciphering their heterogeneity at single cell level, learning how cancer persisters differ from microbial persisters, modeling of the dynamics of persistent cells, and identifying contribution of immune escape mechanisms in driving cancer persisters. This meeting will bring together researchers who study non-genetic drug tolerance in various contexts and who are not used to interacting with each other to discuss key questions in the field and lay the foundations for generating a community dedicated for the study of nongenetic tolerance/resistance. We anticipate that this will result in potential collaborative projects, ideas for sharing the concepts discussed in the meeting with the greater scientific community through publications, and aspirations for future follow-up meetings focused at this exciting emerging field.

The most important factor that limits the success of anti-cancer therapy is the emergence of drug resistance; for instance, median survival of 30-36 months with vemurafenib in BRAFmutant melanoma yet > 1/3rd of patients die within 2 years. Until recently, most of the studies to date (as well as most conferences) were focused on studying the contribution of genetic mechanisms of evolution in drug resistance. However, we seem to have reached a limit in terms of characterizing genetic mutations that give rise to acquired resistance across multiple cancer types. It has become clear from numerous lines of recent evidence that beyond genetics, nongenetic/functional mechanisms that also contribute to resistance development. Similar to bacterial cells in response to antibiotic resistance, cancer cells also acquire a persister state to escape drug pressure. The emergence of persister population can occur via different mechanisms including epigenetic plasticity, metabolic reprogramming, itochondrial unpriming, immune escape, and others at bulk and single-cell levels. Despite important similarities in, and differences between, mechanisms of drug tolerance in bacteria and in cancer cells, few opportunities exist for leaders in these two related fields to interact in a meaningful way. Therefore, this meeting could provide a unique opportunity to gather experts working on microbial and cancer persistence, to define phenotypes, emergent mechanisms, and targeting strategies to overcome non-genetic resistance mechanisms.

The goal of this meeting is to bring together experts from fields of epigenetics, metabolism, single cell omics and microbial and cancer persisters fields to facilitate the discussion to define the functional phenotype of cancer persisters, discuss innovative models to study persisters, and devise novel strategies to target this rare minimal disease (MRD)like cells. By bringing clinicians and translational biologists together, we hope to come up with studies that can provide strong clinical evidence of the xistence of persister population across different tumor types and discuss ways to target it to prevent disease recurrence. This meeting will bring together biologists, bacteriologists, translational scientists, and clinicians to discuss emerging concepts in the non-genetic cancer resistance field and lay the foundation for a cohesive framework to study them. This meeting will provide a unique opportunity to create the intellectual infrastructure and common ground that is needed to propel the field forward. For the first time, this forum will also provide a unique opportunity to bring together scientists from cancer persistence and microbial persistence fields and enable interdisciplinary discussions on how lessons from antimicrobial resistance can help to study and conceptualize cancer persisters.

Forum Summary

Venue & Travel Information

Castello Dal Pozzo

Via Visconti 8
28040 Oleggio Castello, Italy

www.castellodalpozzo.com
+39-0322-53713

Travel Forms

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

The Malpensa Airport (MXP) is the preferred airport as it is only 25 minutes from the meeting location.

The Foundation will be providing airport transfer from MXP airport.

TRAVEL FORMS DUE:
April 12, 2024
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:
April 12, 2024
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

Shruti
Bhatt
,
PhD
Dana-Farber Cancer Institute
Joan
Brugge
,
PhD
Harvard Medical School
Mark
Dawson
,
MBBS, BMedSci, FRACP, FRCPA, PhD
Peter MacCallum Cancer Centre
Doug
Green
,
PhD
St Jude Children's Research Hospital
Matt
Hangauer
,
PhD
University of California San Diego
Aaron
Hata
,
MD, PhD
Harvard University
A-Rum
Kim
,
PhD
University of North Carolina
Anthony G.
Letai
,
MD, PhD
Dana-Farber Cancer Institute
Kim
Lewis
,
PhD
Northeastern University
Catherine
O'Brien
,
MD, PhDFRCSC
Princess Margaret Cancer Center
Yaara
Oren
,
Tel Aviv University
Csaba
Pal
,
PhD
Biological Research Centre
Arjun
Raj
,
PhD
University of Pennsylvania
Caroline
Robert
,
MD, PhD
Gustave Roussy Cancer Campus
Mariangela
Russo
,
PhD
University of Turin, Italy
Sydney
Shaffer
,
MD, PhD
University of Pennsylvania
Sabrina
Spencer
,
PhD
University of Colorado
Adam
Wolpaw
,
MD, PhD
Children's Hospital of Philadelphia
Kris Cameron
Wood
,
PhD
Duke University

Forum Scholars

Yogesh Goyal, PhD
Northwestern University
Eran Hodis, MD, PhD
Dana-Farber Cancer Institute and Mass General Hospital
Arum Kim, PhD
University of North Carolina at Chapel Hill