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It has recently been described that alternative oncogenic drivers may be found in KRAS wild-type ( KRAS WT ) pancreatic cancers. This study aimed to determine the incidence of targetable gene fusions present in KRAS WT pancreatic adenocarcinoma and response to targeted therapy., Methods: One hundred consecutive patients with pancreatic adenocarcinoma who underwent targeted next-generation sequencing using DNA sequencing with RNA sequencing (n = 47) or without RNA sequencing (n = 53) at a single institution were included in the study. The frequency and landscape of targetable fusions in KRAS WT pancreatic adenocarcinoma was characterized and compared with the frequency of fusions in KRAS -mutated ( KRAS MUT ) pancreatic adenocarcinoma. Results were validated in two independent cohorts using data from AACR GENIE (n = 1,252) and TCGA (n = 150). The clinical history of fusion-positive patients who received targeted treatment is described., Results: Pancreatic cancers from 13 of 100 patients (13%) were found to be KRAS WT . Targetable fusions were identified in 4/13 (31%) KRAS WT tumors compared with 0/87 (0%) KRAS MUT pancreatic adenocarcinomas ( P = .0002). One patient with a novel MET fusion had a complete response to targeted therapy with crizotinib that is ongoing at 12+ months of treatment. In the validation cohorts, gene fusions were identified in 18/97 (19%) and 2/10 (20%) KRAS WT tumors reported in the AACR GENIE and TCGA cohorts, respectively., Conclusion: Oncogene fusions are present in KRAS WT pancreatic adenocarcinomas at an increased frequency when compared with KRAS MUT pancreatic adenocarcinomas. As these fusions may be susceptible to targeted therapy, molecular analyses for the detection of fusions in KRAS WT pancreatic adenocarcinomas may warrant increased consideration., (© 2021 by American Society of Clinical Oncology.)

Pharmacogenomics, ie, the study of how an individual's genomic profile influences his or her response to drugs, has emerged as a clinical tool to optimize drug therapy. Certain variants in some genes increase the risk of severe, life-threatening adverse effects from certain drugs. Integrating pharmacogenomics into clinical practice to assist in drug selection and dosing has the potential to improve the outcomes of treatment, reduce the risk of drug-induced morbidity and death, and be cost-effective., (Copyright © 2020 The Cleveland Clinic Foundation. All Rights Reserved.)

Purpose: While there is growing scientific evidence for and significant advances in the use of genomic technologies in medicine, there is a significant lag in the clinical adoption and sustainability of genomic medicine. Here we describe the findings from the National Human Genome Research Institute's (NHGRI) Implementing GeNomics In pracTicE (IGNITE) Network in identifying key constructs, opportunities, and challenges associated with driving sustainability of genomic medicine in clinical practice., Methods: Network members and affiliates were surveyed to identify key drivers associated with implementing and sustaining a genomic medicine program. Tallied results were used to develop and weigh key constructs/drivers required to support sustainability of genomic medicine programs., Results: The top three driver-stakeholder dyads were (1) genomic training for providers, (2) genomic clinical decision support (CDS) tools embedded in the electronic health record (EHR), and (3) third party reimbursement for genomic testing., Conclusion: Priorities may differ depending on healthcare systems when comparing the current state of key drivers versus projected needs for supporting genomic medicine sustainability. Thus we provide gap-filling guidance based on IGNITE members' experiences. Although results are limited to findings from the IGNITE network, their implementation, scientific, and clinical experience may be used as a road map by others considering implementing genomic medicine programs.

Introduction: Moffitt Cancer Center's Personalized Medicine Clinical Service (PMCS) reviews somatic next-generation sequencing (NGS) assay results, provides interpretations, and identifies potential therapeutic options. The number of individuals reviewed by our clinical service who are eligible for on-label or off-label drug therapy based on genetic test results has previously not been quantitated. We determined the number of patients harboring an actionable mutation that would qualify a patient for an on-label drug or consideration for off-label drug treatment., Methods: The Food and Drug Administration (FDA) Table of Pharmacogenomic Biomarkers in Drug Labeling was utilized to identify anticancer agents containing genomic markers in the Indications and Usage section of the drug label. A database containing discrete NGS patient data was queried retrospectively for those drugs and associated genomic mutations included in this study. On-label was defined as those patients who were eligible for a drug based on harboring a targetable mutation in the FDA-approved cancer type. Off-label was defined as those patients who may be considered for a drug based on harboring a targetable mutation in a non-FDA-approved cancer type., Results: A total of 1072 patients and 1131 NGS results were eligible for study inclusion. Fifty-two patients (4.9%) had results for more than one NGS assay. Seventeen drugs targeting ALK, BRAF, BRCA1/BRCA2, EGFR, or ERBB2 mutations met the study inclusion criteria. Of the entire patient population, 92 (8.6%) unique patients were eligible for at least one on-label drug; off-label use of at least one drug could be considered in 103 (9.6%) unique patients., Conclusion: Combining both on-label and off-label opportunities, 175 (16.3%) unique patients had actionable mutations in six genes. Because most patients reviewed by our PMCS have previously treated advanced disease with limited treatment options, identifying additional lines of therapy is of clinical utility., (© 2017 Pharmacotherapy Publications, Inc.)

One of the initial steps for implementing pharmacogenomics into routine patient care is selecting an appropriate clinical laboratory to perform the testing. With the rapid advances in genotyping technologies, many clinical laboratories are now performing pharmacogenomic testing. Selection of a reference laboratory depends on whether a particular genotype assay is already performed by an internal health care organization laboratory or only available externally. Other factors for consideration are coverage of genomic variants important for the patient population, technical support, and cost. In some instances, the decision to select a particular reference laboratory may be the responsibility of the clinician who is recommending genomic interrogation. Only limited guidance is available that describes the laboratory characteristics to consider when selecting a reference laboratory. We provide practical considerations for selecting a clinical laboratory for pharmacogenomic testing broadly categorized into four domains: pharmacogene and variant selection; logistics; reporting of results; and test costs along with reimbursement., (© 2017 Pharmacotherapy Publications, Inc.)

Background: The increasing practicality of genomic sequencing technology has led to its incorporation into routine clinical practice. Successful identification and targeting of driver genomic alterations that provide proliferative and survival advantages to tumor cells have led to approval and ongoing development of several targeted cancer therapies. Within many major cancer centers, molecular tumor boards are constituted to shepherd precision medicine into clinical practice., Materials and Methods: In July 2014, the Clinical Genomics Action Committee (CGAC) was established as the molecular tumor board companion to the Personalized Medicine Clinical Service (PMCS) at Moffitt Cancer Center in Tampa, Florida. The processes and outcomes of the program were assessed in order to help others move into the practice of precision medicine., Results: Through the establishment and initial 1,400 patients of the PMCS and its associated molecular tumor board at a major cancer center, five practical lessons of broad applicability have been learned: transdisciplinary engagement, the use of the molecular report as an aid to clinical management, clinical actionability, getting therapeutic options to patients, and financial considerations. Value to patients includes access to cutting-edge practice merged with individualized preferences in treatment and care., Conclusions: Genomic-driven cancer medicine is increasingly becoming a part of routine clinical practice. For successful implementation of precision cancer medicine, strategically organized molecular tumor boards are critical to provide objective evidence-based translation of observed molecular alterations into patient-centered clinical action. Molecular tumor board implementation models along with clinical and economic outcomes will define future treatment standards. The Oncologist 2017;22:144-151 Implications for Practice: It is clear that the increasing practicality of genetic tumor sequencing technology has led to its incorporation as part of routine clinical practice. Subsequently, many cancer centers are seeking to develop a personalized medicine services and/or molecular tumor board to shepherd precision medicine into clinical practice. This article discusses the key lessons learned through the establishment and development of a molecular tumor board and personalized medicine clinical service. This article highlights practical issues and can serve as an important guide to other centers as they conceive and develop their own personalized medicine services and molecular tumor boards., (© AlphaMed Press 2017.)

Cleveland Clinic (OH, USA) launched the Center for Personalized Healthcare in 2011 to establish an evidence-based system for individualizing care by incorporating unique patient characteristics, including but not limited to genetic and family health history information, into the standard medical decision-making process. Using MyFamily, a web-based tool integrated into our electronic health record, a patient's family health history is used as a surrogate for genetic, environmental and behavioral risks to identify those with an elevated probability of developing disease. Complementing MyFamily, the Personalized Medication Program was created for the purpose of identifying gene-drug pairs for integration into clinical practice and developing the implementation tools needed to incorporate pharmacogenomics into the clinical workflow. We have successfully implemented the gene-drug pairs HLA-B*57:01-abacavir and TPMT-thiopurines into patient care. Our efforts to establish personalized medical care at Cleveland Clinic may serve as a model for large-scale integration of personalized healthcare.

Research on genes and medications has advanced our understanding of the genetic basis of individual drug responses. The aim of pharmacogenomics is to develop strategies for individualizing therapy for patients, in order to optimize outcome through knowledge of the variability of the human genome and its influence on drug response. Pharmacogenomics research is translational in nature and ranges from discovery of genotype-phenotype relationships to clinical trials that can provide proof of clinical impact. Advances in pharmacogenomics offer significant potential for subsequent clinical application in individual patients; however, the translation of pharmacogenomics research findings into clinical practice has been slow. Key components to successful clinical implementation of pharmacogenomics will include consistent interpretation of pharmacogenomics test results, availability of clinical guidelines for prescribing on the basis of test results, and knowledge-based decision support systems.

Benjamin Q Duong,1 Meghan J Arwood,2 J Kevin Hicks,3 Amber L Beitelshees,4 Francesco Franchi,5 John T Houder,2 Nita A Limdi,6 Kelsey J Cook,7,8 Aniwaa Owusu Obeng,9 Natasha Petry,10 Sony Tuteja,11 Amanda R Elsey,2 Larisa H Cavallari,2 Kristin Wiisanen2 on behalf of the IGNITE Network1Department of Precision Medicine, Nemours/Alfred I. DuPont Hospital for Children, Wilmington, DE, USA; 2Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics & Precision Medicine, University of Florida College of Pharmacy, Gainesville, FL, USA; 3Department of Individualized Cancer Management, Moffitt Cancer Center, Tampa, FL, USA; 4Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA; 5Department of Cardiology, University of Florida College of Medicine, Jacksonville, FL, USA; 6University of Alabama School at Birmingham, Birmingham, AL, USA; 7Department of Pharmacotherapy and Translational Research, University of Florida College of Pharmacy, Jacksonville, FL, USA; 8Department of Precision Medicine, Nemours Children’s Specialty Care, Jacksonville, FL, USA; 9The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 10Department of Pharmacy Practice, North Dakota State University College of Health Professions, Fargo, ND, USA; 11Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USACorrespondence: Kristin WiisanenDepartment of Pharmacotherapy and Translational Research and Center for Pharmacogenomics & Precision Medicine, University of Florida College of Pharmacy, P.O. Box 100486, Gainesville, FL 32610-0486, USATel +1 352-273-5114Email kwiisanen@cop.ufl.eduIntroduction: Clinical adoption of genomic medicine has lagged behind the pace of scientific discovery. Practice-based resources can help overcome implementation challenges.Methods: In 2015, the IGNITE (Implementing GeNomics In pracTicE) Network created an online genomic medicine implementation resource toolbox that was expanded in 2017 to incorporate the ability for users to create targeted implementation guides. This expansion was led by a multidisciplinary team that developed an evidence-based, structured framework for the guides, oversaw the technical process/build, and pilot tested the first guide, CYP2C19-Clopidogrel Testing Implementation.Results: Sixty-five resources were collected from 12 institutions and categorized according to a seven-step implementation framework for the pilot CYP2C19-Clopidogrel Testing Implementation Guide. Five months after its launch, 96 CYP2C19-Clopidogrel Testing Implementation Guides had been created. Eighty percent of the resources most frequently selected by users were created by IGNITE to fill an identified resource gap. Resources most often included in guides were from the test reimbursement (22%), Implementation support gathering (22%), EHR integration (17%), and genetic testing workflow steps (17%).Conclusion: Lessons learned from this implementation guide development process provide insight for prioritizing development of future resources and support the value of collaborative efforts to create resources for genomic medicine implementation.Keywords: pharmacogenomics, CYP2C19, clopidogrel, implementation, precision medicine, personalized medicine, clinical pharmacogenomics, CYP2D6