Epigenetics & Drug Therapy

Scott
Armstrong
,
MD, PhD
Dana-Farber Cancer Institute
Steven
Henikoff
,
PhD
Fred Hutchinson Cancer Research Center

Forum Description

Cancer development is a multi-step process with mutations in proto-oncogenes and tumor suppressor genes playing a well-defined role. In this regard, cancer is a genetic disease. However, cellular mechanisms that control the differentiation state, survival and self-renewal of cancer cells are often independent of mutations in DNA sequence and are increasingly recognized as critical for tumor development and progression. These epigenetic mechanisms are largely a result of the multitude of chromatin modifications that control gene expression. Since epigenetic changes are largely reversible, there is significant hope that therapies targeting these modifications may be particularly effective anti-tumor agents.

The influence of chromatin structure on gene activity has been appreciated for decades, and experiments performed in model organisms have clearly demonstrated a role for chromatin structure during normal development. Indeed, the control of chromatin modifications is central to the activation and inactivation of gene expression programs that control cell fate decisions. Activation or repression of gene expression during development is controlled by an intricate and highly complex set of histone and DNA modifications that are determined by specific enzymes such histone methyltransferases, acetyltransferases, demethylases, and deacetylases among others. It is becoming increasingly clear that chromatin-modifying enzymes critical for normal development are also critical for cancer development. The influence of epigenetics in cancer biology ranges from a direct role in disease initiation where epigenetic regulators are mutated leading to aberrant gene expression, to a role in disease progression and drug resistance where widespread abnormalities in chromatin structure influence tumor behavior and therapeutic response. As a specific enzyme controls each of the chromatin modifications, there is tremendous potential for new drug development if we can determine which enzymes are controlling cancer causing gene expression programs in which cancers. Along these lines, recent trials have demonstrated clinical efficacy of histone deacetylase inhibitors and DNA methyltransferase inhibitors providing evidence that targeting epigenetic programs can be effective. Importantly, these new therapies targeting epigenetic mechanisms are well tolerated. This work lays the foundation for what will hopefully be an ever expanding number of new therapies that target epigenetic control of gene expression in cancer cells.

The 2011 Forum to be led by Dr. Steven Henikoff of the Fred Hutchison Cancer Research Center and Howard Hughes Medical Institute, and Dr. Scott Armstrong of Children’s Hospital Boston and Harvard Medical school will provide an opportunity to discuss the current state of the biology of epigenetic gene regulation, and how we can apply this knowledge to develop new therapeutic approaches for cancer patients.

Forum Summary

The focus of the 2011 Forbeck Foundation forum was on the role of epigenetic mechanisms in cancer development and therapy. Epigenetic mechanisms refer to heritable changes in cellular processes that are not a result in changes of DNA sequence. While cancer development can clearly be driven by mutations in proto-oncogenes and tumor suppressor genes, cellular mechanisms that control the differentiation state, survival and self-renewal of cancer cells are often independent of mutations in DNA sequence and are increasingly recognized as critical for tumor development and progression. These epigenetic mechanisms are largely a result of the multitude of chromatin modifications that control gene expression. Since epigenetic changes are largely reversible, there is significant hope that therapies targeting these modifications may be particularly effective anti-tumor agents. The influence of chromatin structure on gene activity has been appreciated for decades, and experiments performed in model organisms have clearly demonstrated a role for chromatin structure during normal development. Indeed, the control of chromatin modifications is central to the activation and inactivation of gene expression programs that control cell fate decisions. Activation or repression of gene expression during development is controlled by an intricate and highly complex set of histone and DNA modifications that are determined by specific enzymes such histone methyltransferases, acetyltransferases, demethylases, and deacetylases among others. It is becoming increasingly clear that chromatin-modifying enzymes critical for normal development are also critical for cancer development. The influence of epigenetics in cancer biology ranges from a direct role in disease initiation where epigenetic regulators are mutated leading to aberrant gene expression, to a role in disease progression and drug resistance where widespread abnormalities in chromatin structure influence tumor behavior and therapeutic response. As a specific enzyme controls each of the chromatin modifications, there is tremendous potential for new drug development if we can determine which enzymes are controlling cancer causing gene expression programs in which cancers. Along these lines, recent trials have demonstrated clinical efficacy of histone deacetylase inhibitors and DNA methyltransferase inhibitors providing evidence that targeting epigenetic programs can be effective. Importantly, these new therapies targeting epigenetic mechanisms are well tolerated. This work lays the foundation for what will hopefully be an ever expanding number of new therapies that target epigenetic control of gene expression in cancer cells. The 2011 Forum brought together a group of experts in Epigenetics to discuss progress and future directions that might lead to a better understanding of cancer biology and to the development of new therapeutic opportunities. The first session was chaired by Steve Henikoff and focused on epigenetic control of gene expression. The presentations in this session prompted a detailed discussion as to the role of epigenetic, particularly histone, modifications in the control of gene expression. Questions arose as to whether the modifications initiate changes in gene expression or are placed as a result of changes in gene expression, but then might be more involved in maintenance of expression of gene expression during developmental fate decisions.

Dr. Steven Henikoff discussed the cause-effect relationship between gene expression and changes in the chromatin landscape. The most conspicuous components of the landscape are nucleosomes, which consist of histone cores that tightly wrap DNA for packaging purposes, but which must be mobilized to allow for DNA replication, transcription into RNA and DNA repair. Nucleosomes are disrupted and sometimes lost and replaced during these dynamic processes, and he showed work from his group that allows the dynamics to be measured genome-wide at high resolution. The evolutionarily conserved pathway for replacing nucleosomes when they are lost has recently been found to be defective in a wide variety of human cancers, which suggests that a better understanding of this pathway and its components have the potential of leading to general therapeutic strategies against cancer.

Dr. Charles Roberts discussed the SWI/SNF chromatin remodeling complexes and their role in cancer development. Growing evidence indicates that these complexes serve a widespread role in tumor suppression as inactivating mutations in several SWI/SNF subunits have recently been identified at high frequency in a variety of cancers. However, the mechanisms whereby mutations in these complexes drive tumorigenesis are unclear. He reviewed the contributions of SWI/SNF mutations to cancer formation, and their normal function in chromatin remodeling and transcriptional regulation. These newly discovered mutations may provide opportunities for novel therapeutic interventions for SWI/SNF mutant cancers. Dr. Jonathan Whetstine discussed the highly dynamic nature of nuclear structure and organization during cell division and cell fate specification. In addition to being highly dynamic, the architecture and chromatin states must be properly organized, placed and inherited so that catastrophic events such as DNA damage and cell fate changes are avoided. Thus certain chromatin modifiers and remodelers may have a preferential role in establishing, creating and perpetuating these chromatin states as cells undergo division, and therefore might protect cells from either DNA damage or inappropriate cell fate decisions which are fundamental aspects of cancer formation. He used histone demethylases to highlight the above mentioned relationships.

Dr. Joseph Costello discussed DNA methylation changes that occur during progression of glioblastoma using epigenomic profiling and detection of copy number variation. He described the involvement of the MGMT (O6-methylguanine DNA methyltransferase) which in normal cells is a DNA repair enzyme that removes damaging lesions from DNA bases and so protects from carcinogens. However in tumors, the action of this enzyme can also protect from killing by chemotherapeutic agents. Therefore, epigenetic silencing of the MGMT gene promoter by DNA methylation is associated with a more favorable outcome. Scholar Alvaro Rada Eglasias discussed how cellular diversity arises during mammalian embryogenesis from a single set of genetic information (i.e. the genome) with a focus on the role of enhancer regions. It is becoming increasingly clear that enhancers play a preponderant role in the establishment of cell-type and developmental-stage specific gene expression patterns. Enhancers are basically short DNA sequences with multiple binding sites for TFs representing the final effectors of signaling pathways as well as for cell-type/developmental-stage specific TFs. In addition, enhancer sequences are subject to epigenetic modifications that can modulate their activity. Therefore, within a short stretch of DNA, enhancers can integrate the regulatory information provided by the three major players involved in the generation of cell-type specific gene expression profiles. He presented some recent advances in epigenomics that allow characterizing enhancers in a sequence conservation and cell-type independent manner. These new findings might allow us to better appreciate the overall role of enhancers during cancer development.

A session chaired by Dr. Scott Armstrong focused on the genes mutated in human cancer that directly influence epigenetic programs such as MLL-fusion proteins and MYC oncoprotein. These talks prompted detailed discussions regarding whether mutations in these genes lead to direct deregulation of specific critical gene expression programs or whether they lead to widespread low-amplitude changes in gene expression that allow the establishment via genetic or other epigenetic abnormalities of a program that in essence sensitizes cells to oncogenic transformation. Dr. Scott Armstrong discussed recent data that demonstrate histone modifications influenced by the Mixed Lineage Leukemia (MLL) protein may play a fundamental role in the pathogenesis of certain leukemias. Rearrangements of the MLL gene are found in a subset of pediatric and adult acute lymphoid and myeloid leukemia (ALL and AML). Leukemias with MLL-rearrangements tend to have a poor prognosis. Several fusion partners of MLL, such as, AF9, AF10, and ENL have been shown to bind and potentially recruit a different histone methyl transferase, DOT1L, which methylates histone 3 on lysine 79 (H3K79). This prompts the hypothesis that certain MLL-fusions transform cells in part by mis-targeting DOT1L, and promoting inappropriate histone methylation. A number of groups have recently demonstrated that inactivation of DOT1L in MLL-fusion driven leukemias leads to specific down regulation of MLL-fusion target genes with very few other changes in gene expression. Suppression of the leukemogeneic program leads to differentiation of leukemia cells, and inhibits leukemia development. These experiments demonstrate the importance of DOT1L in MLL-rearranged leukemias and suggest that small molecule inhibitors of DOT1L might represent a new therapeutic opportunity in this disease. Dr. Bruno Amati discussed the Myc oncoprotein and the fact that it targets thousands of genomic loci. While its expression is frequently deregulated in cancer cells, Myc is tightly controlled by growth-regulatory signals in normal cells, and is required for the cellular response to mitogenic stimuli. In spite of a wealth of information on Myc-target genes, the Myc-dependent transcriptional programs involved in mitogenesis and cancer progression, as well as their overlap largely remain to be identified. He discussed the combination of genome-wide Myc-DNA interaction maps with gene expression profiling as a method to dissect the transcriptional programs controlled by Myc in Myc-induced lymphomas in Em-myc transgenic mice. Only a small fraction of the Myc-bound loci showed Myc-dependent regulation of gene expression, and these genes represent the “core” Myc targets likely to be critical for Myc's biological function in leukemia/lymphoma.

Dr. Chris Kemp discussed a role for the highly conserved Ctcf DNA-binding protein in cancer development. Ctcf plays important roles in multiple aspects of gene regulation including transcription regulation, chromatin insulation, genomic imprinting, X-chromosome inactivation, and higher order chromatin organization. He discussed a newly developed Ctcf knockout mouse model and examined their susceptibility to spontaneous and environmentally induced tumorigenesis. Relative to wild type littermates, Ctcf+/- hemizygous mice showed increased susceptibility to spontaneous, ionizing radiation, and chemically-induced neoplasia in multiple lineages including tumors of epithelial, mesenchymal, and hematopoietic origin. Tumors from Ctcf+/- mice were of higher grade, invasive, and metastatic. Retention of the wild type Ctcf allele and maintenance of functional Ctcf RNA and protein expression in tumors from Ctcf+/- mice establishes Ctcf as a haploinsufficient tumor suppressor gene. Increased DNA methylation was seen at Ctcf. These results establish that Ctcf buffers against environmentally triggered epigenetic changes, providing a potent barrier to both cancer initiation and subsequent malignant progression.

Scholar Grant Challen discussed the role of DNA methylation in blood stem cells. Using conditional ablation, he showed that loss of Dnmt3a progressively impedes hematopoietic stem cell (HSC) differentiation, while simultaneously expanding HSC numbers in the bone marrow. Dnmt3a-null HSCs manifest both increased and decreased methylation at distinct loci, including dramatic CpG island hypermethylation. He also showed that Dnmt3a-null HSCs are unable to methylate and transcriptionally repress HSC multipotency genes in response to chemotherapeutic ablation of the hematopoietic system, leading to inefficient differentiation and manifesting hypomethylation and incomplete repression of HSC-specific genes in their limited differentiated progeny. These data show that Dnmt3a plays a specific role in permitting HSC differentiation, and in its absence, phenotypically normal but impotent stem cells accumulate and differentiation capacity is progressively lost. In light of the recently-identified DNMT3A mutations in AML and MDS patients, these studies are the first biological models linking mutation of Dnmt3a with inhibition of HSC differentiation which may be one of the first pathogenic steps occurring in such patients. Scholar Gary Hon discussed global DNA hypomethylation in cancer. Examining single nucleotide resolution methylome maps, he demonstrated widespread hypomethylation in several breast cancer cell lines compared to a primary mammary epithelial cell line. Notably, hypomethylation is localized to large domains that are frequently shared between several cancer lines. The loss of DNA methylation in these regions is accompanied by formation of repressive chromatin, with a significant fraction displaying allelic DNA methylation where one allele is DNA methylated while the other allele is occupied by histone modifications H3K9me3 or H3K27me3. These results suggest that global DNA hypomethylation is linked to the formation of repressive chromatin domains and gene silencing, thus identifying a potential epigenetic pathway for gene regulation in cancer cells.

A session chaired by Dr. Thea Tlsty focused on the relationships between normal developmental programs and cancer development. This session assessed the role of epigenetics in cancer from a perspective of normal development gone awry. There was significant discussion about abnormalities in DNA methylation as a predisposing event to cancer development. This session also outlined details in regard to gene silencing by polycomb complexes that are proving to be important in cancer development and maintenance in many tissues. Dr. Thea Tlsty discussed DNA methylation and its role in the initiation of breast cancer development. She discussed how changes in DNA methylation are seen early in the oncogenic process and that these changes influence expression critical tumor suppressor and oncogenes thus allowing a cellular state that is primed for full-blown cancer development. These studies prompted discussion about the possibility of identifying such changed in breast or other tissues as a mechanism to identify individuals at higher risk for tumor development. Dr. Stuart Orkin led a discussion about the diverse roles of PRC2 complexes in normal and cancer development. He discussed studies demonstrating a role for PRC2 components as critical for cancer development in some tissues whereas loss of PRC2 components leads to cancer development in other tissues. These studies highlight the complexity and cell type specific aspects of epigenetic mechanisms and suggest that newly developed therapies that target PRC2 complexes will need to take into account the contextual influence on PRC2 function.

Dr. Jean-Pierre Issa discussed the epigenome in aging cells (DNA methylation instability, chromatin instability). Comparison of rodent, primate and human aging shows that DNA methylation instability is conserved, depends primarily on chronologic age, and can be predicted to a certain degree by local genomic features. It can therefore be argued that this epigenomic instability is a necessary result of the evolution of complex genomes that lack reprogramming capabilities in adult cells. Epigenetic instability creates gene expression variation in aging tissues that could contribute to cancer development. Importantly, it can be modulated by exposures (inflammation and perhaps diet), providing a mechanistic link between lifestyle and disease. In turn, epigenetic reprogramming could be useful for prevention and treatment of age-related pathology. Dr. Maarten van Lohuizen discussed the Polycomb-group (Pc-G) protein complexes and the counteracting Trithorax-group (Trx-G) of histone modifying factors which are involved in the dynamic maintenance of proper gene expression patterns during development. When deregulated, these master switches of gene expression are strongly implicated in formation of a diverse set of cancers. Using genome wide assessment of chromatin structure he demonstrated that polycomb domains interact in 3D nuclear space and are guided by chromosome architecture. He also discussed recent discoveries demonstrating a role for an E3 ubiquitin ligase in the PRC1 complex suggesting this might be a therapeutic target in multiple cancers. The implications of these findings for stem cell biology, development, and possibilities for new translational approaches to cancer are broad as the PRC1 complex is known to be critical for many different types of cancer.

Scholar Chris Vakoc discussed the development of a non-biased approach to probe epigenetic vulnerabilities in acute myeloid leukemia. By screening a custom library of small hairpin RNAs (shRNAs) targeting known chromatin regulators in a genetically defined AML mouse model, he identified the protein bromodomain-containing 4 (Brd4) as being critically required for disease maintenance. Suppression of Brd4 using shRNAs or the small-molecule inhibitor JQ1 lead to robust anti-leukemic effects in vitro and in vivo, accompanied by terminal myeloid differentiation and elimination of leukemia stem cells. Similar sensitivities were observed in a variety of human AML cell lines and primary patient samples, revealing that JQ1 has broad activity in diverse AML subtypes. The effects of Brd4 suppression are, at least in part, due to its role in sustaining Myc expression to promote aberrant self-renewal, which implicates JQ1 as a pharmacological means to suppress MYC in cancer. These results establish small-molecule inhibition of Brd4 as a promising therapeutic strategy in AML and, potentially, other cancers, and highlight the utility of RNA interference (RNAi) screening for revealing epigenetic vulnerabilities that can be exploited for direct pharmacological intervention.

A session chaired by Ari Melnick focused on the potential therapeutic ramifications of our expanded understanding of the roles of epigenetic mechanisms in cancer development. In this session we discussed how DNA methylation profiles can be used to identify unique cancer subtypes and also to predict therapeutic response. We also discussed exciting new small molecules that target chromatin modifying enzymes, and that are likely to be assess in clinical trials in the not too distant future. Dr. Ari Melnick discussed how acute myeloid leukemias (AMLs) can be classified according to epigenetic signatures affecting DNA methylation or histone modifications. He described recent work that demonstrates heterozygous somatic mutations in the loci encoding isocitrate dehydrogenase 1 and 2 (IDH1/2) which occur in ~20% of AMLs and are accompanied by global DNA hypermethylation and hypermethylation and silencing of a number of specific gene promoters. He also discussed how recent data link TET2 with the function of cytosine deaminases as a pathway towards DNA demethylation, which has implications as well for B-cell lymphomas and CML lymphoid blast crisis, which are linked with the actions of activation induced cytosine deaminase. Altogether, the available data implicate mutations in IDH1/2 and TET2 in promoting malignant transformation in several tissues, by disrupting epigenomics programming and altering gene expression patterning.

Dr. Ross Levine discussed a series of candidate gene and whole genome studies that have identified recurrent somatic mutations in AML, MDS, and MPN patients including TET2, ASXL1, DNMT3A, and EZH2 mutations. He discussed recent studies demonstrating the effects of ASXL1 mutations on chromatin state, gene expression, and hematopoietic function, and identified a specific role for ASXL1 in regulating H3K27 trimethylation and PRC2 function at specific loci in hematopoietic cells including at the HoxA cluster. He also showed that hematopoietic specific loss of ASXL1 loss leads to myeloid transformation in vivo. These data demonstrate that novel mutations co-opt the epigenetic state of hematopoietic stem/progenitor cells in order to contribute to transformation. Data from recent in vitro and in vivo studies delineating the role of TET2 and ASXL1 mutations in the pathogenesis of myeloid malignancies will be presented in detail. Dr. Jay Bradner discussed recent studies from his lab where they have developed small molecule inhibitors of epigenetic “reader” proteins that bind histones with specific modifications. They have developed small molecules that interact with the bromodomains in BRD4 and inhibit BRD4 function. Remarkably, these small molecules suppress MYC protein expression and thus effectively inhibit proliferation of a number of different cancer cell lines in a MYC dependent fashion. These studies have prompted rapid movement of these molecules toward clinical translation in leukemia, myeloma and other cancers.

Dr. Victoria Richon discussed recent development of the DOT1L inhibitor EPZ004777, a small molecule with sub-nanomolar affinity for this enzyme and >1000-fold selectivity against other histone methyltransferases. EPZ004777 selectively inhibits intracellular histone H3K79 methylation in a concentration and time dependent manner. Significant changes in genes expression were observed in MLL-rearranged cell lines following 4 days of inhibitor treatment. This timing is consistent with the timing of the effects of EPZ004777 on histone H3K79 methylation. Phenotypically, EPZ004777 inhibits proliferation and induces apoptosis in human MLL-rearranged leukemia cell lines after 7 to 10 days, with little effect on non-MLL-translocated cells. In vivo administration of EPZ004777 leads to extension of survival in a mouse MLL xenograft model. Thus, EPZ004777 provides compelling validation for the development of DOT1L inhibitors as targeted therapeutics for MLL-rearranged leukemia.

In summary the 2011 Forbeck Foundation Research Forum was viewed as a tremendous success by all that attended. There was tremendous excitement that the approaches discussed by the participants will lead to a greater understanding of cancer development. Furthermore there are already tangible examples of small molecules and new drugs that are beginning to make a difference for cancer patients. There is the expectation that there are more to come in the near future.

Venue & Travel Information

Hilton Head Island

Travel Forms

TRAVEL FORMS DUE:
October 3, 2011
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 3, 2011
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

Bruno
Amati
,
PhD
Instituto Italiano di Techologia
Stephen B.
Baylin
,
MD
Johns Hopkins Oncology Center
Jay
Bradner
,
MD
Dana-Farber Cancer Institute
Lewis C.
Cantley
,
PhD
Beth Isreal Deaconess Medical Center
Joe
Costello
,
Md
UCSF
Jean-Pierre
Issa
,
MD
MD Anderson
Ari
Melnick
,
MD
Cornell University
Stuart H.
Orkin
,
MD
Chairman, Dept of Pediatric Oncology
Victoria
Richon
,
PhD
Epizyme Inc
Charlie
Roberts
,
MD, PhD
Dana-Farber Cancer Institute
Thea
Tlsty
,
PhD
UCSF
Maarten
van Lohuizen
,
The Netherlands Cancer Institute
Johnathan R.
Whetstine
,
PhD
Harvard Medical School and Massachusetts General Hosp Ctr
Eileen
White
,
PhD
Rutgers Cancer Institute
Yi
Zhang
,
PhD
UNC Chapel Hill

Forum Scholars

Grant Challen, PhD
Washington University
Gary Hon, PhD
University of California San Diego
Alvaro Rada-Iglesias, PhD
Stanford University