Epigenetic Therapy

Stephen B.
Baylin
,
MD
Johns Hopkins Oncology Center
Jean-Pierre
Issa
,
MD
MD Anderson
Peter
Jones
,
PhD D.Sc
Van Andel Research Institute

Forum Description

Epigenetics is the study of stable patterns of gene expression that determine cellular identity. Epigenetic information is substantially altered by multiple mechanisms in cancer cells. An important development in the field has been the ability to reprogram the epigenome through drugs that target the epigenetic machinery (epigenetic therapy). Early positive results with DNA methylation and Histone Deacetylase inhibitors led to an explosion of drug development, with more than 30 drugs targeting more than 6 different pathways currently in early stage clinical trials. Epigenetic reprogramming is also viewed as an exciting way to reverse drug resistance and sensitize cancers to chemotherapy and immunotherapy.

There are key basic and translational issues that remain unsolved in the field, particularly as it is moving to wide acceptance in combination clinical trials. Which epigenetic target will provide optimal chemo or immunosensitization? What are the mechanisms of response and resistance to this therapy? Are the effects of epigenetic “priming” through modulation of tumor or host cell epigenetics?

The 2017 Forum on Epigenetic Therapy will be co-chaired by Dr. Jean-Pierre Issa of Temple University, Dr. Stephen Baylin of Johns Hopkins University and Dr. Peter Jones of Van Andel Research Institute. It will bring together investigators with expertise in diverse areas (different epigenetic targets, immunotherapy, basic investigators, clinical-translational investigators) to discuss how synergies across different fields can help move epigenetic therapy forward to improve cancer outcomes.

Forum Summary

The meeting theme was to explore targets, drugs, combinations, and mechanisms of response to epigenetic therapy in cancer. All 16 presentations addressed aspects of this theme. The first session concerned established therapies including DNA methylation inhibitors and histone deacetylase inhibitors. Peter Jones summarized mechanisms of gene silencing by DNA methylation and gene activation by inhibition of these enzymes, including translational data showing that activation of endogenous retroviruses was associated with in-vivo responses.

Stephen Baylin showed how epigenetic mechanisms are used by cancer cells to provide a selective advantage for growth and invasion, and he showed how this can be interrupted by simultaneous targeting of DNMTs and HDACs. Lucy Godley discussed the role of TETs in dynamic processes including the hypoxia response in different cancer models and how this could contribute to cancer progression. Kristian Helin presented data from a new CAS9 screen for selective killing of AML cells, focusing on new epigenetic targets.

The second session continued the theme of new targets with presentations by Ali Shilatifard (who discussed new drugs target the COMPASS proteins), Cigall Kadoch (who summarized existing data on the SWI/SNF family of proteins’ role in cancer, including possible ways by which they can be targeted), Jean-Pierre Issa (who described a new drug targeting CDK9) and Nada Jabado (who summarized how mutations in histones lead to cancer development and how this can lead to therapeutic approaches through synthetic lethalities). The third session focused on combinations of epigenetic therapies with other treatments, including chemotherapy. Faye Rassool showed how DNMT and PARP inhibitors are synergistic, including new data on downregulation of DNA repair pathways by DNMT inhibitors, leading to sensitivity to PARP inhibitors. Kenneth Nephew presented data obtained from a clinical trial of DNMT inhibition combined with chemotherapy in ovarian cancer that showed promising clinical results. He proposed novel approaches by which clinical results of epigenetic therapy can be enhanced, including through combinations that target the tumor microenvironment. Rugang Zhang also discussed therapies in ovarian cancer, focusing on the subset of tumors that carry epigenetic mutations (e.g. ARID1A) and how these can be targeted through synthetic lethalities with other epigenetic targets.

Charles Roberts continued on this theme, extending it to multiple other mutations in the SWI/SNF pathways, discussing how these alter the epigenome and create vulnerabilities to other therapies. The final session focused on the emerging field of immunosensitization by epigenetic therapies, in part through misregulation of silenced repetitive elements. Matthew Lorincz summarized what is known about the regulation of epigenetic silencing at retrotransposons and other repeats, and how this can be disrupted in cancer. Daniel DeCarvalho reviewed the concept of activation of repetitive elements as a key mechanism of the anti-tumor activity of DNMT inhibitors and showed new data on dissecting the specific elements mediating this effect. Shelley Berger showed recent data on potential immunosensitization by inactivation of TET2 in T-lymphocytes and on oncogenic roles of activating P53 mutations. The final speaker was Yang Shi who presented recent data on immunosensitization by targeting LSD1. The final session was a group discussion that focused on the most promising approaches presented, and on how to prioritize targets for clinical testing and drug development based on pre-clinical studies.

Lay summary
Epigenetic therapy refers to treatments aimed at changing the nature of cancer cells by manipulating the instructions that govern their cellular identity. Over the past few years, this field has led to many drugs that are being tested in clinical trials, some of which have made it all the way to FDA approval. The meeting focused on expanding these successes by understanding better how current therapies work, by discovering new ways to target epigenetics, and by designing therapy combinations that exploit the effects of the drugs on cellular identity and phenotypes. An emerging theme of the meeting was the effects of epigenetic therapies on the immune system, and on designing therapies based on therapeutic vulnerabilities created by mutations in epigenetic effectors, or by drugs that inactivate these effectors.

Venue & Travel Information

Geneva National Resort

1221 Geneva National Avenue, South

Lake Geneva, WI 53147

262-245-7000

Travel Forms

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

Milwaukee's General Mitchell International Airport (MKE) is the preferred airport as it is only 45 minutes from the meeting location.

  • Arrivals - Thursday around 1 PM, 3 PM and 5 PM
  • Departures - Sunday around 10 AM and 12 PM

Chicago's O'Hare Airport (ORD) is 1 1/2 hours from the meeting location without traffic. The Foundation tries to prioritize International Flights and situations where flying into ORD is significantly cheaper than connecting to MKE. The times below are for guidance only, and depending on the volume of travelers, we may add an additional shuttle to and from the airport.

  • Arrivals - Thursday around 3 PM
  • Departures - Sunday around 10 AM
TRAVEL FORMS DUE:
August 27, 2018
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:
August 27, 2018
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

Shelley L.
Berger
,
PhD
University of Pennsylvania Pearlman School of Medicine
Daniel
De Carvalho
,
PhD
Princess Margaret Cancer Centre
Lucy A.
Godley
,
MD, PhD
Northwestern University
Kristian
Helin
,
Biotech Research & Innovation Centre and University of Copenhagen
Nada
Jabado
,
MD, PhD
Research Institute of the McGill University Health Center
Cigall
Kadoch
,
PhD
Dana-Farber Cancer Institute
Matthew
Lorincz
,
PhD
University of British Columbia
Kenneth P.
Nephew
,
PhD
Indiana University
Feyruz V.
Rassool
,
PhD
University of Maryland
Charles
Roberts
,
MD, PhD
St. Jude Children's Research Hospital
Padmanee
Sharma
,
MD, PhD
MD Anderson Cancer Center
Yang
Shi
,
PhD
Harvard Medical School
Ali
Shilatifard
,
PhD
Northwestern, Feinberg School of Medicine
Rugang
Zhang
,
PhD
The Wistar Institute

Forum Scholars

No Scholars attended this meeting