Tuesday, May 5
7:00 am Conference Registration and Morning Coffee
8:00 Chairperson’s Opening Remarks
G. Mike Makrigiorgos, Ph.D., Professor, Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School
8:10 Talk Title to be Announced
Matthias Holdhoff, M.D., Ph.D., Assistant Professor, Oncology, Medicine and Neurosurgery, Brain Cancer Program, SKCCC, Johns Hopkins University
8:35 Detection of Somatic Mutations in Biological Fluids in the Management of Cancer
Nickolas Papadopoulos, Ph.D., Professor, Ludwig Center, SKCCC, Johns Hopkins University
Somatic mutations are cancer specific biomarkers that reveal the presence of cancer when present in cell-free DNA or DNA derived from biological fluids. The number of circulating tumor DNA molecules with somatic mutations is very low compared to that of DNA molecules with wild-type sequence and requires very sensitive methods for their detection. Here we discuss our efforts for developing such methods, studies for their validation, and their clinical applications.
9:00 cfDNA Ultra-Rare Allele Detection and Discovery
Seth Crosby, M.D., Director, Partnerships & Alliances, Washington University School of Medicine
9:25 Pharmacodynamic Assessment of Drug Response by Monitoring Mutational Load in Urinary Circulating Tumor DNA
Karena Kosco, Ph.D., Principal Scientist, Research and Development, Trovagene
The concept of liquid biopsies is expanding to include urine as a specimen type. Using Precision Cancer MonitoringSM (PCM) platform for quantitative ctDNA analysis at a single copy level, we demonstrate that drug-induced immediate early changes in ctDNA mutational load correlate with tumor burden and treatment response. As a non-invasive specimen, urine enables frequent monitoring of ctDNA, and this accessibility can be applied to investigating mechanisms of action of targeted therapeutics and, ultimately, cancer management.
9:55 Q&A with the Speakers
10:10 Coffee Break in the Exhibit Hall with Poster Viewing
10:40 Ultrasensitive Measurement of Circulating Tumor DNA to Assess Treatment Response and Resistance
Abhijit A. Patel, M.D., Ph.D., Assistant Professor, Therapeutic Radiology, Yale University School of Medicine
Our group has developed an ultrasensitive, multi-target assay that can identify and quantify mutant ctDNA using novel error-suppression techniques applied to next-generation sequencing data. Broad coverage of mutation hotspots and warm-spots allows detection of ctDNA without prior knowledge of the tumor’s mutation profile. Clinical examples will be presented in which this approach is used to noninvasively monitor changes in ctDNA levels in response to treatment and to track the emergence of mutations that confer resistance to targeted therapies.
11:05 Single-Tube Enrichment of Mutations in Cancer Gene Panels from Circulating DNA, Using COLD-PCR Prior to Targeted Amplicon Resequencing
G. Mike Makrigiorgos, Ph.D., Professor, Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School
Targeted re-sequencing of mutations in cancer-relevant genes provides opportunities for fine-tuning cancer therapy and follow-up during treatment, by examining mutations in tumors and bio-fluids. However, a major technical limitation has been the lack of sensitivity of cancer re-sequencing panels for mutations below 1-2% abundance, which is frequently the case for circulating DNA. We present a newly developed method via which mutations in numerous amplicons are first enriched via COLD-PCR in a single-tube reaction, prior to targeted re-sequencing. Using this approach, mutations of 0.01-0.1% abundance can be detected via next-generation sequencing.
11:35 Panel Discussion
Moderator: G. Mike Makrigiorgos, Ph.D., Professor, Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School
12:00 pm Enjoy Lunch on Your Own
1:30 Chairperson’s Remarks
Nazneen Aziz, Ph.D., Chief Research Officer & Senior Vice President, Phoenix Children’s Hospital
1:35 Application of NGS for Biomarker Discovery and Patient Selection
Xiaolan Hu, Ph.D., Head, Clinical Genetics, Bristol-Myers Squibb
2:00 Phoenix Children’s Hospital to Address the Unmet Need: Slow Progress in Pediatric Drug Development
Nazneen Aziz, Ph.D., Chief Research Officer & Senior Vice President, Phoenix Children’s Hospital
The need for new drugs in pediatric cancer is acute. Virtually no new therapy has been introduced in the past two decades. Treatment for relapsed patients is lower than in adults yet a large number of childhood cancer patients will relapse. In stark contrast to the rapid introduction of targeted therapies in adults more effective therapies are unavailable in pediatric cancer. PCH will focus on genomic analysis to better understand disease mechanisms to develop new therapeutics for pediatric cancer.
2:25 A General Approach to the Discovery and Translation of Multi-Gene Biomarkers in Drug Discovery and Therapy
Wolfgang Sadee, Dr.rer.nat., Professor & Director, College of Medicine Center for Pharmacogenomics, The Ohio State University
Extensive genetics/genomics studies have yet to account for the estimated heritability of complex traits, including diseases and their treatments. Our discovery pipeline encompasses detailed molecular genetics of target genes – to avoid use of surrogate markers – and large-scale data analytics to reveal phenotype associations involving gene-gene-environment interactions. Discovering frequent regulatory variants in key genes often under positive selection, we are now in a position to develop clinically relevant biomarker panels, demonstrated with examples.
2:50 A Novel Phospho-Proteomic Diagnostic for Patient Stratification and Therapy Selection for Breast Cancer
Glenn Hoke, Ph.D., Executive Vice President and COO, Theranostics Health™, Inc.
The TheraLink® Assay for Breast Cancer, a commercially available CAP/CLIA test, measures the proteomic signature in patient’s cancer, to provide the activation status for multiple drug targets. Designed for use in the routine clinical setting, this molecular diagnostic assay can identify which patients are more likely to respond to a particular molecularly targeted therapy. Case studies and the design of a prospective trial will be presented.
3:20 Refreshment Break in the Exhibit Hall with Poster Viewing
4:10 Utility of Targeted NGS Panels for Cancer in an Academic Molecular Pathology Laboratory
Helen Fernandes, Ph.D., Associate Professor, Pathology and Laboratory Medicine, Weill Cornell Medical College
The utility of targeted next-generation sequencing-based assays for identification of genomic variants has made significant advances in the field of molecular oncology. Testing panels and platforms have enabled clinical molecular pathology laboratories to expand their testing menu to include NGS assays that can provide information for a more reliable prediction of personalized cancer therapies. Additionally, the assays can identify relevant genes that may have implications for enrollment of the patient in clinical trials. This presentation will focus on the issues involved for optimal performance and implementation characteristics of assays for the identification of somatic variants in solid tumors in an academic molecular pathology laboratory.
4:35 Patient Stratification in Oncology Using NGS: An Application of the PATH™ Analytics Platform to AML Patients from TCGA
Tobi Guennel, Ph.D., Principal, Analytics, Precision for Medicine
Molecular heterogeneity in tumors is expected to impact prognosis and response to therapy, and the ability to stratify patients based on their underlying molecular profiles can improve outcomes. The transformation of high-dimensional genomic data into personalized treatments requires cutting-edge science and advanced analytics. To help biopharmaceutical companies realize this goal, Precision for Medicine has developed the PATH™ Analytics Platform, a multi-modal platform designed to accelerate research on biomarker discovery and patient stratification by combining advanced Bayesian analytics and real-time data exploration.
5:00-6:00 Welcome Reception in the Exhibit Hall with Poster Viewing
Wednesday, May 6
8:00 am Morning Coffee
8:25 Chairperson’s Remarks
George Vasmatzis, Ph.D., Assistant Professor, Laboratory Medicine and Pathology, Mayo Clinic
8:30 Use of Biomarkers for Decision-Making in Breast Cancer Therapy
Dennis J. Slamon, M.D., Ph.D., Chief, Hematology & Oncology, The David Geffen School of Medicine, University of California, Los Angeles
8:55 The Impact of Multiplexed Genotyping in Directing Cancer Care and a Role for Combining Genotype with Histology for Biomarker Discovery
Darrell R. Borger, Ph.D., Director, Biomarker Laboratory, Massachusetts General Hospital and Harvard Medical School
Our laboratory has conducted clinical genotyping in a large academic hospital for 7 years, and we have started to evaluate its impact on expanding targeted therapy options for cancer patients. With the integration of next-generation sequencing technologies, more complex genotypes are now being identified. Subsequently, the integration of histological testing may provide important perspective into the biological function of unknown variants and the ability to identify new biomarkers of response.
9:20 From Discovery Through Commercialization of Personalized Multiplex Biomarker Assays
Al Akowitz, Ph.D., Vice President, Strategic Sales, Meso Scale Discovery
9:50 Coffee Break in the Exhibit Hall with Poster Viewing
10:45 Genomic Markers Associated with Pathologic Complete Response and Resistance in Triple Negative Breast Cancer
Christos Hatzis, Ph.D., Assistant Professor, Medicine; Director, Bioinformatics, Breast Medical Oncology, Yale University School of Medicine
Efforts to develop transcriptional predictors of chemotherapy sensitivity in triple negative breast cancer (TNBC) have been met with limited success due to the heterogeneity of this disease. We explored whether genomic differences in the exomes of extremely chemotherapy sensitive and highly chemotherapy resistant TNBC cases could provide clues of chemosensitivity. Although a few genes show response-associated mutational patterns, the chemoresistant cases appear to have higher mutational load and subclonal heterogeneity, suggesting that higher DNA diversity may be associated with chemotherapy resistance. Interestingly, resistant tumors show characteristic mutational spectrum shifts that may suggest heterogeneous branch evolution. These broad measures of genomic diversity could show promise as markers of resistance to chemotherapy.
11:10 Comprehensive Translational Research to Identify Predictive Biomarkers of Lenvatinib in the Preclinical and Clinical Study
Yasuhiro Funahashi, Ph.D., Senior Director, Biomarkers and Personalized Medicine, Eisai
This presentation will cover: 1) systems biology to identify biomarker candidates for Lenvatinib using the cancer cell line panel, 2) translational research to test biomarker candidates in multiple Phase II trials, and 3) biomarker correlative analysis in Phase III trial.
11:35 Identification of Independent Primary Lung Tumors and Intrapulmonary Metastases Using DNA Junctions
George Vasmatzis, Ph.D., Assistant Professor, Laboratory Medicine and Pathology, Mayo Clinic
Distinguishing independent primary tumors from intrapulmonary metastases in non-small-cell carcinoma remains a clinical dilemma with significant clinical implications. Using next-generation DNA sequencing, we developed a chromosomal rearrangement-based approach to differentiate multiple primary tumors from metastasis. Tumor specimens from patients with known independent primary tumors and metastatic lesions were used for lineage test development, which was then applied to multifocal cases. Lung tumors predicted to be independent primary tumors based on different histologic subtype did not share any genomic rearrangements. In cases of lung primary tumor and paired distant metastasis, shared rearrangements were identified in all cases, emphasizing the patient specificity of identified breakpoints. Concordance between histology and genomic data occurred in the majority of cases. Discrepant cases were resolved by genome sequencing. A diagnostic lineage test based on genomic rearrangements from mate-pair sequencing demonstrates promise for distinguishing independent primary from metastatic disease in lung cancer.
12:00 pm Close of Conference