Showing papers by "Jonathan W. Simons published in 2020"

Accelerating precision medicine in metastatic prostate cancer.

Abstract: Despite advances in the screening and treatment of prostate cancer, the therapy options available, particularly for later stages of the disease, remain limited, and the treatment-resistant setting represents a serious unmet medical need. Moreover, disease heterogeneity and disparities in patient access to medical advances result in considerable variability in outcomes across patients. Disease classification based on genomic sequencing is a promising approach for identifying patients whose tumors exhibit actionable targets and for making more informed treatment decisions. Here we discuss how precision oncology can be accelerated to inform broader genomically driven clinical decisions for men with advanced prostate cancer, to inform drug development and, ultimately, to contribute to new treatment paradigms. Beltran and colleagues discuss the challenges in treating metastatic prostate cancer and strategies to accelerate precision oncology and improve therapy and clinical decisions in this setting.

Prostate cancer research: The next generation; report from the 2019 Coffey-Holden Prostate Cancer Academy Meeting.

Abstract: Introduction The 2019 Coffey-Holden Prostate Cancer Academy (CHPCA) Meeting, "Prostate Cancer Research: The Next Generation," was held 20 to 23 June, 2019, in Los Angeles, California. Methods The CHPCA Meeting is an annual conference held by the Prostate Cancer Foundation, that is uniquely structured to stimulate intense discussion surrounding topics most critical to accelerating prostate cancer research and the discovery of new life-extending treatments for patients. The 7th Annual CHPCA Meeting was attended by 86 investigators and concentrated on many of the most promising new treatment opportunities and next-generation research technologies. Results The topics of focus at the meeting included: new treatment strategies and novel agents for targeted therapies and precision medicine, new treatment strategies that may synergize with checkpoint immunotherapy, next-generation technologies that visualize tumor microenvironment (TME) and molecular pathology in situ, multi-omics and tumor heterogeneity using single cells, 3D and TME models, and the role of extracellular vesicles in cancer and their potential as biomarkers. Discussion This meeting report provides a comprehensive summary of the talks and discussions held at the 2019 CHPCA Meeting, for the purpose of globally disseminating this knowledge and ultimately accelerating new treatments and diagnostics for patients with prostate cancer.

Minimum Technical Data Elements for Liquid Biopsy Data Submitted to Public Databases.

Abstract: Minimum Technical Data Elements for Liquid Biopsy Data Submitted to Public Databases Phillip G. Febbo, Anne-Marie Martin, Howard I. Scher, J. Carl Barrett, Julia A. Beaver, Paul J. Beresford, Gideon M. Blumenthal, Kelli Bramlett, Carolyn Compton, Ryan Dittamore, David A. Eberhard, Daniel Edelstein, James Godsey, Andrew Gruen, Sean E. Hanlon, James Hicks, Daniel Hovelson, Melanie Hullings, Donald Johann, Justin Johnson, Anand Kolatkar, Peter Kuhn, Rebecca Levine, Jean-Francois Martini, Daniel P. Miller, Carissa Moore, Bryan Moy, Anand Pathak, Reena Philip, David Reese, Wendy Royalty, Matthew Ryder, Hakan Sakul, Lea M. Salvatore, Andrew Schade, Angela Silvestro, John K. Simmons, Jonathan Simons, Seema Singh Bhan, Matthew D. Smalley, Stella B. Somiari, AmirAli Talasaz, Muneesh Tewari, Hsian-Rong Tseng, Jake Vinson, Walt Wells, Allison Welsh, Robert L. Grossman*,, Jerry S. H. Lee and Lauren C. Leiman

Feasibility of Integrating Canine Olfaction with Chemical and Microbial Profiling of Urine to Detect Lethal Prostate Cancer

Abstract: Prostate cancer is the second leading cause of cancer death in men in the developed world. A more sensitive and specific detection strategy for lethal prostate cancer beyond serum prostate specific antigen (PSA) population screening is urgently needed. Diagnosis by canine olfaction, using dogs trained to detect cancer by smell, has been shown to be both specific and sensitive. While dogs themselves are impractical as scalable diagnostic sensors, machine olfaction for cancer detection is testable. However, studies bridging the divide between clinical diagnostic techniques, artificial intelligence, and molecular analysis remains difficult due to the significant divide between these disciplines. We tested the clinical feasibility of a cross-disciplinary, integrative approach to early prostate cancer biosensing in urine using trained canine olfaction, volatile organic compound (VOC) analysis by gas chromatography-mass spectroscopy (GC-MS) artificial neural network (ANN)-assisted examination, and microbial profiling in a double-blinded pilot study. Two dogs were trained to detect Gleason 9 prostate cancer in urine collected from biopsy-confirmed patients. Biopsy-negative controls were used to assess canine specificity as prostate cancer biodetectors. Urine samples were simultaneously analyzed for their VOC content in headspace via GC-MS and urinary microbiota content via 16S rDNA Illumina sequencing. In addition, the dogs’ diagnoses were used to train an ANN to detect significant peaks in the GC-MS data. The canine olfaction system was 71% sensitive and between 70-76% specific at detecting Gleason 9 prostate cancer. We have also confirmed VOC differences by GC-MS and microbiota differences by 16S rDNA sequencing between cancer positive and biopsy-negative controls. Furthermore, the trained ANN identified regions of interest in the GC-MS data, informed by the canine diagnoses. Methodology and feasibility are established to inform larger-scale studies using canine olfaction, urinary VOCs, and urinary microbiota profiling to develop machine olfaction diagnostic tools. Scalable multi-disciplinary tools may then be compared to PSA screening for earlier, non-invasive, more specific and sensitive detection of clinically aggressive prostate cancers in urine samples.