PMO Live 2015 – Highlights from Wednesday July 22
Welcome to the 2015 Fourth Annual PMO Live Conference!
Welcome to the 2015 Fourth Annual PMO Live Conference, a joint program of the Global Biomarkers Consortium (GBC) and the World Cutaneous Malignancies Congress. The GBC, whose theme is “Molecular Biomarkers for Precision Medicine in Oncology: Recent Advances and Future Perspectives,” consists of a community of world-renowned healthcare professionals, assembled to explore the clinical application of novel molecular pathways and prognostic and predictive molecular biomarkers in oncology, leading to delivery of personalized care for cancer patients.
The Fourth Annual Meeting of the Global Biomarkers Consortium is dedicated to providing an understanding of molecular pathway and biomarker research in hematology and oncology, as well as the clinical impact of emerging data on clinical practice. Co-chaired by Drs. Jorge Cortes and Hope Rugo, this Congress features an international faculty who will provide a thorough understanding of the current and future landscape of tumor biomarkers, and how to effectively personalize cancer care in managing patients with solid tumors and hematologic malignancies. “I’m looking forward to productive and stimulating discussions with a great agenda and faculty,” said Dr. Cortes in his opening remarks. “There have been over 100,000 publications on candidate cancer biomarkers, so there is a pressing need for this meeting to make sense of all of this.”
A Primer of the Clinical Application of Molecular Biomarkers: What to Order and How to Use the Results
GBC 2015 was opened by the meeting co-chairs, Drs. Jorge Cortes and Hope Rugo, to a record attendance. The opening session of the meeting was titled A Primer on the Clinical Application of Molecular Biomarkers: What to Order and How to Use the Results, which explored in very practical terms the genetic variability of cancer and how to optimally use this information to facilitate precision oncology care. Dr. Michael Kattan opened the session with a presentation on bioinformatics, highlighting differences among prognostic, predictive, and pharmacodynamic biomarkers. This was followed by a guide to cancer genomics and proteomics presented by Drs. Katherine Hoadley and Towia Libermann, who are both experts in translational research and precision medicine, in which they provided their perspectives on integrative genomic and proteomic analyses to better understand novel molecular pathways in cancer, and how to best use this information in developing approaches to personalized therapy. In addition, they showed how to integrate comprehensive functional genomics strategies with systems biology to define disease mechanisms at a molecular level and identify novel biomarkers, drug targets, and therapeutics for cancer. “We need prognostic biomarkers to avoid overtreatment of clinically indolent cancers and undertreatment of aggressive cancers,” Dr. Libermann suggested. The final presentation in this session was by Dr. Mark Sausen, who reviewed the methodologies currently available and in development for biomarker testing. His talk focused on novel tissue- and cell-free DNA-based genomic approaches for the detection and analysis of cancer. A lively panel discussion with questions from attendees rounded out this session. “This was a great overview of molecular biomarkers,” opined an attendee as he rose to ask a question. The faculty panel and attendees then engaged in lively discussion of whether biomarkers for cancer prevention, early detection, or cure would be the most useful and cost-effective.
A Keynote Presentation on Exploring Molecular Pathways in Cancer
Dr. Adjei reviewed cancer cell signaling pathways, the cellular processes they regulate, and how this information has led to the development of novel targeted agents for cancer, using non–small-cell lung cancer (NSCLC) as a model. However, he cautioned that not all “oncogenic” mutations are predictive biomarkers, and suggested that clinical studies are required to investigate the relationship between oncogenic mutations and sensitivity to therapeutic agents targeting those mutations, again using NSCLC as a model. He concluded that molecular pathways in cancer can be exploited for therapy, with sensitizing genetic aberrations as the ideal targets, but there is much work yet to be done to explore drug combinations as well as new targets and therapeutic modalities.
What’s New in Cancer Biomarker Research?
Dr. Jerald Radich, a member of the Clinical Research Division and Director of the Molecular Oncology Lab at the Fred Hutchinson Cancer Research Center, and Professor of Medicine at the University of Washington School of Medicine, reviewed emerging efforts in identifying and utilizing novel molecular biomarkers to inform cancer therapy, focusing on techniques nearing commercialization that have shown promise in clinical studies. To contrast Dr. Radich’s presentation, Dr. Philip Mack, Director of the UC Davis Cancer Center Molecular Pharmacology Shared Resource, spoke about cancer biomarkers in preclinical development, focusing on patient-derived xenograft (PDX) models for translational cancer research. Using NSCLC as an example, Dr. Mack spoke about PDX NSCLC models tested to date, and the fact that they can recapitulate histology, genetics, and clinical activity observed in patients, allow determination of contributions of individual drugs in a regimen, and provide insight into molecular effects of drugs. Moreover, PDX models are expected to help identify specific molecular impediments to successful drug outcomes, allow iterative processes to improve treatment strategies for cancer patients, and serve as an incubator for clinical trial concepts. These provocative presentations elicited numerous questions from attendees, including clinicians and basic scientists, demonstrating the intense interest in molecular biomarkers in cancer.
A Case-Based Discussion of Innovative Molecular Pathways and Biomarkers in Treating Solid Tumors
This strictly clinical session focused on presentations of typical cases in melanoma by Dr. Sanjiv Agarwala, lung cancer by Dr. Mark Socinski, breast cancer by Dr. Joyce O’Shaughnessy, and colorectal cancer by Dr. William Grady, with a discussion by the experts regarding how they would manage patients with these solid cancers to achieve personalized care. These dynamic “Expert’s Perspective” presentations engaged the attendees in making management decisions on the use of molecular biomarkers in real-life cases in these tumor types, using the latest data from the literature and recent meetings to support and explain why certain management decisions are made. The “this is how I would do it” approach has been a huge audience favorite at GBC, and the medical oncologists in the audience engaged in a dynamic discussion during this session. Dr. Agarwala opened his presentation by stating, “In the era of biomarker-driven immunotherapy, chemotherapy is obsolete in treating metastatic melanoma.” He then reviewed data on anti–CTLA4 and anti–PD-1 immune checkpoint therapy in advanced melanoma. Moreover, Dr. Agarwala showed data in BRAF-mutated patients and suggested that “BRAF is a valuable biomarker in melanoma that tells you what NOT to do for your patient.” Dr. Socinski followed with a thorough review of the value of a number of molecular biomarkers that have been used to inform therapy in lung cancer including EGFR, ALK, ROS, BRAF, MET, and RET. Dr. O’Shaughnessy’s presentation started with the suggestion that in breast cancer, there are no validated biomarkers that can drive therapy. Nevertheless, she reviewed the genotypes of breast cancer patients that have exceptional responses to certain targeted agents, particularly in hard-to-treat triple–negative metastatic breast cancer. Finally, Dr. Grady reviewed the pathogenesis of colorectal cancer (CRC) and the biomarkers that arise as colorectal epithelium progresses from normal, to dysplastic, early and late polyp formation, and metastatic cancer. He also reviewed the molecular heterogeneity of CRC and the clinical application of selected biomarkers in genotyping this malignancy, including microsatellite instability (MSI) testing for prognosis and predicting response to 5-FU-based targeted therapy or anti–PD-1 agents, as well as CIMP, Oncotype DX-colon and ColoPrint testing. Dr. Grady ended by discussing the role of KRAS mutations in driving therapy for CRC. Following the session, Congress participants were afforded a “Meet the Experts” networking opportunity to engage the faculty in an informal setting to discuss issues on molecular biomarkers and personalized medicine in oncology. Congress participants were also able to visit the exhibit booths from Congress supporters. In reviewing the day, it was evident that speakers had fostered debate and discussion, with interaction among basic scientists, clinicians, and other healthcare providers from various disciplines. Much more is coming tomorrow, including a keynote presentation on targeting genetic drivers in premalignancy, case-based discussions of innovative molecular pathways and biomarkers in treating hematologic malignancies, an industry perspective on the use of biomarkers in cancer, the use of molecular biomarkers in early detection of cancer, the impact of molecular biomarkers on clinical trials, and the regulatory and economic aspects of precision medicine in oncology.
In reviewing the day, it was evident that speakers had fostered debate and discussion, with interaction among basic scientists, clinicians, and other healthcare providers from various disciplines. Much more is coming tomorrow, including a keynote presentation on targeting genetic drivers in premalignancy, case-based discussions of innovative molecular pathways and biomarkers in treating hematologic malignancies, an industry perspective on the use of biomarkers in cancer, the use of molecular biomarkers in early detection of cancer, the impact of molecular biomarkers on clinical trials, and the regulatory and economic aspects of precision medicine in oncology.
Thank you to our sponsor!