Research Roundup

Research Roundup

Section Editor:
George Papadopoulos, BSc(Hons), GradDipEpi, MAICD Partner & Director, Lucid Health Consulting & School of Medicine, UNSW, Sydney, NSW, Australia

The articles in this session of Research RoundUp look at precision medicine. Quite the topic!  Precision medicine has held promise for many years as a tailored approach to both disease prevention and treatment that considers the differences in people’s genetic makeup. Genomic sequencing underpins the value of precision medicine in being able to better predict, prevent, diagnose, and treat diseases.  There are more than 750 trials of cell and gene therapies in almost 30,000 patients underway globally as of June 2020, and cell and gene therapies products account for approximately 12% of the pharmaceutical industry’s clinical pipeline. There is an abundance of literature on precision medicine and in this issue, and we have tried to identify recent research that encapsulates these characteristics and is worth reading.

Precision Medicine: Steps Along the Road to Combat Human Cancer
Nassar SF, Raddassi K, Ubhi B, Doktorski J, Abulaban A
Cells. 2020;9(9):2056. https://doi:10.3390/cells9092056.

The authors examine the recent innovations in assays, devices, and software, along with next-generation sequencing in genomics diagnostics that are in use or are being developed for personalized medicine. They begin with a discussion of the lessons learned to date and the current research on pharmacogenomics. The authors take us on a journey from the ancient Chinese, Greek, Roman, and Arabic theories that sought to answer fundamental questions of how and why some individuals either developed or avoided diseases and conditions all the way through to the Human Genome Project and onto the 21st century. In this comprehensive review, the topics explored the benefits of personalized medicine, the progression of precision medicine and positive outcomes, the challenges facing precision medicine, pharmacogenetics and pharmacogenomics, review of technologies and recommendations, and a conclusion of the future promise of precision medicine. The authors also provide a section of examples of precision medicine drugs.

If you don’t read past this first article, then this article will fully ground you in what precision medicine is and its impact now and into the future. Great progress is being made in fighting cancer and the ability to discern, record, and analyze genetic information provides the means to rapidly detect cancer and other diseases earlier and more accurately than ever before and that is the true global perspective on precision medicine.


Health Economics Tools and Precision Medicine: Opportunities and Challenges
Veenstra DL, Mandelblatt J, Neumann P, et al
Forum Health Econ Policy. 1998;23(1):20190013.

Health economics frameworks and tools can elucidate the effects of legal, regulatory, and reimbursement policies on the use of precision medicine while guiding research investments to enhance the appropriate use of precision medicine. This review provides an overview of precision medicine and key policy challenges for the health economics field; explains the potential utility of economics methods in addressing these challenges; describes recent research activities; and summarizes opportunities for cross-disciplinary research. To accomplish this, the authors selected key examples to discuss based on the potential utility of economic approaches for informing precision medicine analyses and policies, and with the intention of helping health economists not currently working in precision medicine understand the applicability of current economics tools in this area.

Precision medicine is evolving at a tremendous pace and this paper provides an overview of the promise of precision medicine and the implications of precision medicine for improved health economics. Examples of the application of economic tools to precision medicine highlight opportunities for economics in precision medicine, as well as important challenges. There are a multitude of economics tools that can be applied to precision medicine to better understand potential benefits, harms, and economic impacts. This paper is worth reading many times over.


Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer
Dreyer SB, Upstill-Goddard R, Paulus-Hock V, et al
Gastroenterology. 2020;1-16.

Pancreatic ductal adenocarcinoma, the more common form of pancreatic cancer, is dominated by mutations in 4 well-known cancer genes (KRAS, TP53, CDKN2A, and SMAD4). Only a few genes are mutated in 5%–15% of cases, amidst an ocean of infrequently mutated genes in the majority of patients. This diversity may explain the lack of progress with targeted therapies, because actionable genomic events being targeted therapeutically are present in only a small proportion of unselected participants in clinical trials. The research builds on previous work on DNA damage-response deficiency, which is a hallmark of cancer—including pancreatic cancer—and aims to expand the indications for novel DNA damage-response inhibitors beyond patients with defects in homologous recombination mechanisms. The aim was to refine proposed DNA damage response biomarkers of platinum response to be tested in prospective clinical trials and to correlate and overlap this with cell-cycle inhibitor response to identify patients who will respond to novel agents, such as ataxia-telangiectasia Rad3-related and WEE1 inhibitors.

This study will end up being a landmark paper. Based on preclinical models of patient-derived cell lines of pancreatic cancer and organoid responses that were generated from patients with pancreatic cancer to develop new molecular markers that can predict who will respond to drugs targeting DNA damage, the findings mark an important step for potential treatment options for pancreatic cancer, improving the options and outcomes for a disease where survival rates have remained the lowest in oncology. This paper highlights the basic and translational research required to enable biomarker-driven clinical testing and allows refinement of biomarkers predicting meaningful responses and potential translation into clinical practice.


The Egyptian Collaborative Cardiac Genomics Project: Defining a Healthy Volunteer Cohort
Aguib Y, Allouba M, Afify A, et al
npj Genom Med. 2020;(5):46.

Cardiovascular disease is a major cause of death and disability worldwide, and its prevalence continues to increase in low- and middle-income countries toward epidemic proportions. The Egyptian Collaborative Cardiac Genomics (ECCO-GEN) Project is recruiting 1000 Egyptian healthy volunteers from the general population who consent to be recalled to future research and are simultaneously establishing a regional biobank that hosts a broad range of biological samples for prospective studies. Participants are fully phenotyped with respect to cardiovascular health. The full dataset of 1000 volunteers will aid in distinguishing between incidental and medically actionable variants, and thus enhance diagnostic and treatment strategies. All individuals underwent detailed clinical investigation, including cardiac magnetic resonance imaging, and were sequenced using a targeted panel of 174 genes with reported roles in inherited cardiac conditions.

The ECCO-GEN project aims at defining the genetic landscape of an understudied population and providing individual-level genetic and phenotypic data to support future studies in cardiovascular disease and population genetics.


Returning Results in the Genomic Era: Initial Experiences of the eMERGE Network.
Wiesner GL, Kulchak Rahm A, Appelbaum P, et al
J Pers Med. 2020;10:30.

The electronic Medical Record and Genomics (eMERGE) Network is addressing the implementation of genomic medicine within the US healthcare system. Established more than 10 years ago, the primary goal of the network has been “to develop, disseminate, and apply approaches to research that combine biorepositories with electronic medical record systems for genomic discovery and genomic medicine implementation research. There is currently no protocol or practice standards for returning unsolicited genetic tests that are identified as a consequence of clinical care or research programs. eMERGE3 emulates the “real world” of genomic medicine today, in which organizations are independently exploring incorporation of genomics into clinical practice and provides an ideal setting to study the return of results (RoR) processes for genomic sequence results that were not solicited by healthcare professionals (HCPs) in a diverse set of healthcare institutions. This paper describes the planned RoR processes independently developed at each of the 10 eMERGE3 sites and examines the similarities and differences in approaches for the disclosure of unsolicited genomic results to participants and their HCPs in order to identify “best practices” for the utilization and return of genomic information within the healthcare system today.

This report on initial ROR processes and experiences across 10 eMERGE3 sites highlights the current real-world needs of healthcare systems in developing new pathways to support genomic medicine. The paper provides a foundation for studying within eMERGE3 and other future studies the impact of these RoR processes on patient, provider, and organization utilization of genomic information.


Drug Use in Denmark for Drugs Having Pharmacogenomics (PGx) Based Dosing Guidelines From CPIC or DPWG for CYP2D6 and CYP2C19 Drug–Gene Pairs: Perspectives for Introducing PGx Test to Polypharmacy Patients
Westergaard N, Søgaard Nielsen R, Jørgensen S, Vermehren C
J Pers Med. 2020;10(1):3.

The cytochrome P450 drug metabolizing enzymes CYP2D6 and CYP2C19 are the major targets for pharmacogenomics testing and determining for drug response. Clinical dosing guidelines for specific drug–gene interactions are publicly available through PharmGKB in Denmark. The aim of this register study is to map the use of drugs in Denmark for drugs having actionable dosing guidelines, ie, dosing recommendations different from standard dosing for CYP2D6 or CYP2C19 drug–gene interactions in terms of consumption. The aim of the study was to map the use of drugs in Denmark by applying Anatomical Therapeutic Chemical codes for drugs having dosing guidelines (CPIC or DPWG) for CYP2D6 and/or CYP2C19, in terms of consumption of defined daily dose.

This research underscores the importance of accessing and accounting for drug-drug interactions, drug-gene interactions, and drug-drug-gene interactions while understanding that it is a complex process demanding multidisciplinary collaborations to obtain infrastructural capacities for good decision-making processes, as well as further studies to assess the economic impact of pre-emptive pharmacogenomics panel testing.

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