Schedule of Events


Friday, October 17, 2014

8:30 AM - 9:30 AM
Breakfast and Registration

Welcome from Laura Thrall
President and CEO, CureSearch


9:30 AM - 11:30 AM
Epigenetics

Remodeling the Remodelers: BAF Complex Structure and Function In Human Malignancy
Recent genome-wide exon sequencing studies have revealed that over 20% of human cancers bear mutations in the genes encoding subunits of mammalian SWI/SNF (or BAF) ATP-dependent chromatin remodeling complexes, making them the most frequently and broadly mutated chromatin regulator. Our studies focus upon cancers with genomically well-defined BAF complex aberrations, such as synovial sarcoma, malignant rhabdoid tumors, and others to uncover the structural and functional consequences of BAF complex perturbation, and to catalyze the identification of therapeutics for this class of tumors.
EZH2 Inhibitors as Novel Cancer Therapeutics
EZH2 is the catalytic subunit of the multi-protein complex known as PRC2. PRC2 catalyzes methylation of the histone 3, lysine 27 (H3K27) site as a mechanism for controlling gene transcription. Dysregulation of H3K27 methylation is oncogenic in a number of human cancers including germinal center-B cell lymphomas and INI1-deficient tumors. We have identified the first potent, selective, orally bioavailable inhibitor of EZH2, EPZ-6438, and have initiated phase 1 clinical testing of this compound.
Targeting Cancer Cell Memory
Cancer develops by inappropriate activation of the cellular growth program. The master regulator of the cancer growth program is an MYC, which activates target genes via regulatory sequences called enhancers. In an effort to understand MYC, we have undertaken to characterize the regulatory landscape of cancer cells through an integrated approach involving genome-wide measurements of enhancer function. Additionally, we have worked to develop therapeutic strategies to target MYC directly and indirectly. This presentation will discuss efforts to target critical co-activators of MYC, called bromodomain proteins.


12:00 PM - 1:30 PM
Opening Lunch

Presentations by Acceleration Initiative One Grantees

Awarding of Young Investigator Two Awards
Announcement of Acceleration Initiative Two Grand Challenges



2:00 PM - 4:00 PM
Supposedly Undruggable Targets

What Mixed Lineage Leukemia Has Helped Teach Us
More than 20 years have passed since the identification of the Mixed Lineage Leukemia or MLL gene (now known as KMT2A). While we have learned a great deal has about the function of the protein under normal conditions, we do not fully understand how mutant versions of the protein specifically transform healthy blood cell precursors into leukemia. Fortunately, gaps in our understanding of the mechanisms by which mutant MLL proteins cause leukemia have not stood in the way of developing exciting new disease-specific treatments.
Intended and Unintended Consequences of Targeted Therapy in Children With Cancer: What is Druggable, What Shouldn't be Touched, and How Will We Know the Difference?
The objectives for this talk will be to discuss both off and on-target side effects that are coming to light in children treated with new cancer therapies. The risks and benefits of some novel agents will be disucssed and the consequences and implications, both short and long-term, will be reviewed. Possible ways to address these observations will be discussed in the context of pediatric oncology clinical trials.
Targeting EWS-FLI1: The Achilles' 'HEAL' of Ewing Sarcoma
Dr. Jeffrey Toretsky has been studying Ewing sarcoma since 1992. His early work investigated minimal residual disease, antisense oligonucleotide growth inhibition, and novel EWS-FLI1 targets and protein interactions. The Toretsky laboratory continues to focus on Ewing sarcoma, since the tumors contain a unique target, EWS-FLI1, which is not found in non-tumor cells. We created the first small molecule to directly target EWS-FLI1, YK-4-279, which is a useful laboratory probe and advancing to clinical trials. The oncologic process set in motion by EWS-FLI1 remains relatively cryptic despite the identification of many transcriptional targets. This presentation will discuss the discovery process of YK-4-279, the status of preclinical investigations, and touch on newly discovered EWS-FLI1 mechanisms.


4:00 PM - 5:00 PM
Young Investigator Presentations


5:30 PM - 7:00 PM
Reception



Saturday, October 18, 2014

8:00 AM - 9:00 AM
Breakfast and Networking


9:00 AM - 10:30 AM
Young Investigator Presentations Continued


10:30 AM - 12:30 PM
Individualized Medicine

Lessons Learned Developing Adult Precision Medicine Clinical Trials
This talk will concentrate on the decisions to be made when designing clinical trials with integral or integrated Next Generation Sequencing assays, using recent and developing NCI sponsored trials. Points will include types of Master Protocols, choice of endpoints, decisions on the intended use and analytical validation of the assay in a clinical laboratory.
Promises, Possibilities and Pitfalls: Lessons Learned from Clinical Exome Sequencing of Pediatric Solid Tumor Patients
Advances in sequencing technologies allow for provision of genome-scale data to clinicians caring for pediatric cancer patients but current experience with the clinical application of genomic sequencing is limited. This presentation will discuss the early results of the BASIC3 (Baylor Advancing Sequencing into Childhood Cancer Care) study, which aims to determine the clinical impact of incorporating CLIA-certified tumor and constitutional whole exome sequencing (WES) into the care of children with newly diagnosed solid tumors.
Tailoring Precision Medicine Concepts to Childhood Cancers
A decade ago it was possible to hope that targetable oncogenes might be identified in a high percentage of childhood cancers. However, it now appears that the majority of childhood cancers (with notable exceptions) will not be found to have activated oncogenes that are targetable with currently available anticancer drugs. The presentation will address how "precision medicine" strategies can be pursued by pediatric oncologists given this evolving perception of the landscape of childhood cancer genomics.


12:30 PM
Closing Remarks