Avenues to Precision Oncology

2020 ◽  
pp. 36-45
Author(s):  
Alexander Meisel
Keyword(s):  
Precision Medicine ◽  
Trial Design ◽  
Ad Hoc ◽  
Molecular Targets ◽  
Clinical Trial Design ◽  
Predictive Biomarkers ◽  
Precision Oncology ◽  
Companion Diagnostics ◽  
Bona Fide ◽  
The One

Until recently, the clinical management of cancer heavily relied on anatomical and histopathological criteria, with ad hoc guidelines directing the therapeutic choices in specific indications. In the last years, the development and therapeutic implementation of novel anticancer therapies significantly improved the clinical outcome of cancer patients. Nonetheless, such cutting-edge approaches revealed the limitation of the one-size-fits-all paradigm. The newly discovered molecular targets can be exploited either as bona fide targets for subsequent drug development, or as tools to precision medicine, in the form of prognostic and/or predictive biomarkers. This article provides an overview of some of the most recent advances in precision medicine in oncology, with a focus on novel tissue-agnostic anticancer therapies. The definition and implementation of biomarkers and companion diagnostics in clinical trials and clinical practice are also discussed, as well as the changing landscape in clinical trial design.

scholarly journals Therapeutic trial design for frontotemporal dementia and related disorders

2018 ◽  
Vol 90 (4) ◽  
pp. 412-423 ◽  
Author(s):  
Philippe Desmarais ◽  
Jonathan D Rohrer ◽  
Quoc Dinh Nguyen ◽  
Nathan Herrmann ◽  
Donald T Stuss ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Precision Medicine ◽  
Frontotemporal Dementia ◽  
Trial Design ◽  
Clinical Trial Design ◽  
Molecular Testing ◽  
Therapeutic Trial ◽  
Negative Results ◽  
Early Phase Clinical Trials ◽  
Randomised Controlled

The frontotemporal dementia (FTD) spectrum is a heterogeneous group of neurodegenerative syndromes with overlapping clinical, molecular and pathological features, all of which challenge the design of clinical trials in these conditions. To date, no pharmacological interventions have been proven effective in significantly modifying the course of these disorders. This study critically reviews the construct and methodology of previously published randomised controlled trials (RCTs) in FTD spectrum disorders in order to identify limitations and potential reasons for negative results. Moreover, recommendations based on the identified gaps are elaborated in order to guide future clinical trial design. A systematic literature review was carried out and presented in conformity with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. A total of 23 RCTs in cohorts with diagnoses of behavioural and language variants of FTD, corticobasal syndrome and progressive supranuclear palsy syndrome were identified out of the 943 citations retrieved and were included in the qualitative review. Most studies identified were early-phase clinical trials that were small in size, short in duration and frequently underpowered. Diagnoses of populations enrolled in clinical trials were based on clinical presentation and rarely included precision-medicine tools, such as genetic and molecular testing. Uniformity and standardisation of research outcomes in the FTD spectrum are essential. Several elements should be carefully considered and planned in future clinical trials. We anticipate that precision-medicine approaches will be crucial to adequately address heterogeneity in the FTD spectrum research.

scholarly journals Translational Research in the Era of Precision Medicine: Where We Are and Where We Will Go

2021 ◽  
Vol 11 (3) ◽  
pp. 216
Author(s):  
Ruggero De Maria Marchiano ◽  
Gabriele Di Sante ◽  
Geny Piro ◽  
Carmine Carbone ◽  
Giampaolo Tortora ◽  
...  
Keyword(s):  
Translational Research ◽  
Precision Medicine ◽  
Large Scale ◽  
Randomized Clinical Trials ◽  
Health Management ◽  
Predictive Biomarkers ◽  
Precision Oncology ◽  
High Definition ◽  
Real World Data ◽  
Promising Alternative

The advent of Precision Medicine has globally revolutionized the approach of translational research suggesting a patient-centric vision with therapeutic choices driven by the identification of specific predictive biomarkers of response to avoid ineffective therapies and reduce adverse effects. The spread of “multi-omics” analysis and the use of sensors, together with the ability to acquire clinical, behavioral, and environmental information on a large scale, will allow the digitization of the state of health or disease of each person, and the creation of a global health management system capable of generating real-time knowledge and new opportunities for prevention and therapy in the individual person (high-definition medicine). Real world data-based translational applications represent a promising alternative to the traditional evidence-based medicine (EBM) approaches that are based on the use of randomized clinical trials to test the selected hypothesis. Multi-modality data integration is necessary for example in precision oncology where an Avatar interface allows several simulations in order to define the best therapeutic scheme for each cancer patient.

scholarly journals Landscape of Biomarkers and Actionable Gene Alterations in Adenocarcinoma of GEJ and Stomach—A Real World Data Analysis

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4453
Author(s):  
Louisa Hempel ◽  
Julia Veloso de Oliveira ◽  
Andreas Gaumann ◽  
Valeria Milani ◽  
Katrin Schweneker ◽  
...  
Keyword(s):  
Real World ◽  
Gastroesophageal Junction ◽  
Molecular Targets ◽  
Scoring Systems ◽  
Subsequent Treatment ◽  
Phase Iii ◽  
Precision Oncology ◽  
Sequencing Data ◽  
Companion Diagnostics ◽  
Real World Data

After several years of negative phase III trials in gastric and esophageal cancer, a significant breakthrough in the treatment of metastatic adenocarcinomas of the gastroesophageal junction (GEJ) and stomach (GC) is now becoming evident with the emerging of precision oncology and implementation of molecular targets in tumor treatment. In addition, new generation studies such as umbrella and basket trials are focused on these molecular targets, which makes an early molecular diagnosis based on IHC/ISH and NGS necessary. The required companion diagnostics of Her2neu overamplification or PD-L1 expression is based on immunohistochemistry (IHC) or additionally in situ hybridization (ISH) in case of an IHC Her2neu score of 2+. However, there are investigator-dependent differences in the assessment of Her2neu amplification and different PD-L1 scoring systems obtained by IHC/ISH. The use of high-throughput technologies such as next-generation sequencing (NGS) holds the potential to standardize the analysis and thus make them more comparable. In the presented study, real-world multigene sequencing data of 72 Caucasian patients diagnosed with metastatic adenocarcinomas of GEJ and stomach were analyzed. In the clinical companion diagnostics, we found ESCAT level I molecular targets in one-third of our patients, which directly determined the therapy. In addition, we found potential targets in 14/72 patients (19.4%) who potentially qualify for precision therapies in corresponding molecular studies. The study highlights the importance of comprehensive molecular profiling for precision treatment of GEJ/GC and indicates that a biomarker evaluation should be performed for all patients with metastatic adenocarcinomas before the initiation of first-line treatment and during second-line or subsequent treatment.

Sign in / Sign up

Export Citation Format

Share Document