scholarly journals Predictive Biomarkers and Clinical Evidence

2021 ◽  
Author(s):  
Jan Trøst Jørgensen
Keyword(s):  
Clinical Evidence ◽  
Predictive Biomarkers

scholarly journals Systematic Review of Recurrent Osteosarcoma Systemic Therapy

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1757
Author(s):  
Ioanna Gazouli ◽  
Anastasios Kyriazoglou ◽  
Ioannis Kotsantis ◽  
Maria Anastasiou ◽  
Anastasios Pantazopoulos ◽  
...  
Keyword(s):  
Clinical Evidence ◽  
Treatment Effectiveness ◽  
Treatment Strategies ◽  
Bone Cancer ◽  
Predictive Biomarkers ◽  
Mtor Inhibitors ◽  
Cytotoxic Chemotherapy ◽  
Driver Mutations ◽  
Preclinical Research ◽  
Primary Bone

Osteosarcoma is the most frequent primary bone cancer, mainly affecting those of young ages. Although surgery combined with cytotoxic chemotherapy has significantly increased the chances of cure, recurrent and refractory disease still impose a tough therapeutic challenge. We performed a systematic literature review of the available clinical evidence, regarding treatment of recurrent and/or refractory osteosarcoma over the last two decades. Among the 72 eligible studies, there were 56 prospective clinical trials, primarily multicentric, single arm, phase I or II and non-randomized. Evaluated treatment strategies included cytotoxic chemotherapy, tyrosine kinase and mTOR inhibitors and other targeted agents, as well as immunotherapy and combinatorial approaches. Unfortunately, most treatments have failed to induce objective responses, albeit some of them may sustain disease control. No driver mutations have been recognized, to serve as effective treatment targets, and predictive biomarkers of potential treatment effectiveness are lacking. Hopefully, ongoing and future clinical and preclinical research will unlock the underlying biologic mechanisms of recurrent and refractory osteosarcoma, expanding the therapeutic choices available to pre-treated osteosarcoma patients.

Evidence-based Molecular Profiling for Solid Tumours – The Future is Now

2012 ◽  
Vol 08 (04) ◽  
pp. 242
Author(s):  
Raheela Ashfaq ◽  
Andreas Voss ◽  
◽  
Keyword(s):  
Drug Response ◽  
Therapeutic Strategy ◽  
Clinical Evidence ◽  
Cancer Genomics ◽  
Predictive Biomarkers ◽  
Molecular Profiling ◽  
Specific Information ◽  
Evidence Based ◽  
Cancer Management ◽  
Cancer Types

Advances in our understanding of the molecular basis of cancer have shown that biomarkers can help guide therapy in a growing number of cancer types and that targeted therapies are becoming increasingly integral to cancer management. However, how to interpret the rapidly expanding wealth of data on cancer genomics and ensure that the best evidence is effectively translated into an optimal individualised therapeutic strategy, remains a challenge. Caris Target Now™ is a well-established, evidence-based molecular profiling service provided by Caris Life Sciences (Basel, Switzerland). Caris Target Now utilises the latest diagnostic molecular assay technologies to determine the unique biomarkers of a patient’s tumour. This is combined with an extensive review of the published clinical evidence to correlate predictive biomarkers with drug response, in order to reveal the potential benefit (or lack of benefit) of specific therapeutic agents. By this process, Target Now provides tumour-specific information that can be used to help physicians personalise cancer therapy for their patients.

scholarly journals Hypoxia and its therapeutic possibilities in paediatric cancers

2020 ◽  
Author(s):  
Carolina Bernauer ◽  
Y. K. Stella Man ◽  
Julia C. Chisholm ◽  
Elise Y. Lepicard ◽  
Simon P. Robinson ◽  
...  
Keyword(s):  
Patient Outcomes ◽  
Clinical Evidence ◽  
Predictive Biomarkers ◽  
Childhood Cancers ◽  
Resonance Imaging ◽  
Paediatric Cancer ◽  
Alternative Therapeutic Approach ◽  
Clinically Significant ◽  
Magnetic Resonance Imaging Mri ◽  
Therapeutic Possibilities

Abstract In tumours, hypoxia—a condition in which the demand for oxygen is higher than its availability—is well known to be associated with reduced sensitivity to radiotherapy and chemotherapy, and with immunosuppression. The consequences of hypoxia on tumour biology and patient outcomes have therefore led to the investigation of strategies that can alleviate hypoxia in cancer cells, with the aim of sensitising cells to treatments. An alternative therapeutic approach involves the design of prodrugs that are activated by hypoxic cells. Increasing evidence indicates that hypoxia is not just clinically significant in adult cancers but also in paediatric cancers. We evaluate relevant methods to assess the levels and extent of hypoxia in childhood cancers, including novel imaging strategies such as oxygen-enhanced magnetic resonance imaging (MRI). Preclinical and clinical evidence largely supports the use of hypoxia-targeting drugs in children, and we describe the critical need to identify robust predictive biomarkers for the use of such drugs in future paediatric clinical trials. Ultimately, a more personalised approach to treatment that includes targeting hypoxic tumour cells might improve outcomes in subgroups of paediatric cancer patients.

Immunotherapy in Advanced Gastroesophageal Tumors: The Best of the Current Knowledge

2019 ◽  
pp. 18-21
Author(s):  
Sara De Dosso
Keyword(s):  
Clinical Evidence ◽  
Current Knowledge ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarkers ◽  
Biologic Agents ◽  
Upper Gi ◽  
Programmed Death ◽  
The Usa ◽  
Deficient Mismatch Repair ◽  
Cell Death Protein

Gastroesophageal cancers have a poor prognosis despite the use of novel therapies, such as chemotherapy combinations and biologic agents. Recently, immune checkpoint inhibitors (ICIs) have also been introduced into the treatment landscape. The programmed cell death protein 1 (PD-1) inhibitor, pembrolizumab, for instance, has been approved in the USA in 2017, with the indication of advanced gastric and esophageal programmed death-ligand 1 (PD-L1)-positive tumors, as well as for deficient mismatch repair or microsatellite instability-high (dMMR/MSI-H) solid tumors.1,2 Signals of outstanding efficacy were particularly observed in biomarker selected populations.3 Hence, there is an urgent need to identify precise predictive biomarkers for optimal patient selection and to establish more effective treatment timings. The present review summarizes the current clinical evidence supporting treatment with ICIs in upper GI tumors.

scholarly journals Implementing TMB measurement in clinical practice: considerations on assay requirements

ESMO Open ◽  
2019 ◽  
Vol 4 (1) ◽  
pp. e000442 ◽  
Author(s):  
Reinhard Büttner ◽  
John W Longshore ◽  
Fernando López-Ríos ◽  
Sabine Merkelbach-Bruse ◽  
Nicola Normanno ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Immune Checkpoint ◽  
Clinical Evidence ◽  
Checkpoint Inhibitors ◽  
Quantitative Measure ◽  
Predictive Biomarkers ◽  
Treatment Decisions ◽  
Response To Therapy ◽  
Sample Type ◽  
Sequencing Platform

Clinical evidence demonstrates that treatment with immune checkpoint inhibitor immunotherapy agents can have considerable benefit across multiple tumours. However, there is a need for the development of predictive biomarkers that identify patients who are most likely to respond to immunotherapy. Comprehensive characterisation of tumours using genomic, transcriptomic, and proteomic approaches continues to lead the way in advancing precision medicine. Genetic correlates of response to therapy have been known for some time, but recent clinical evidence has strengthened the significance of high tumour mutational burden (TMB) as a biomarker of response and hence a rational target for immunotherapy. Concordantly, immune checkpoint inhibitors have changed clinical practice for lung cancer and melanoma, which are tumour types with some of the highest mutational burdens. TMB is an implementable approach for molecular biology and/or pathology laboratories that provides a quantitative measure of the total number of mutations in tumour tissue of patients and can be assessed by whole genome, whole exome, or large targeted gene panel sequencing of biopsied material. Currently, TMB assessment is not standardised across research and clinical studies. As a biomarker that affects treatment decisions, it is essential to unify TMB assessment approaches to allow for reliable, comparable results across studies. When implementing TMB measurement assays, it is important to consider factors that may impact the method workflow, the results of the assay, and the interpretation of the data. Such factors include biopsy sample type, sample quality and quantity, genome coverage, sequencing platform, bioinformatic pipeline, and the definitions of the final threshold that determines high TMB. This review outlines the factors for adoption of TMB measurement into clinical practice, providing an understanding of TMB assay considerations throughout the sample journey, and suggests principles to effectively implement TMB assays in a clinical setting to aid and optimise treatment decisions.

Ultrastructural Study of Human Testicular Biopsies in Infertility

1976 ◽  
Vol 34 ◽  
pp. 156-157
Author(s):  
Shirley Siew ◽  
Philip Troen ◽  
Howard R. Nankin
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Basement Membrane ◽  
Leydig Cells ◽  
Clinical Evidence ◽  
Young Male ◽  
Germinal Epithelium ◽  
Transmission Electron ◽  
Age Range ◽  
Male Subjects

Testicular biopsies were obtained from six young male subjects (age range 24-33) who complained of infertility and who had clinical evidence of oligospermia. This was confirmed on histological examination which showed a broad spectrum from profound hypospermatogenesis to relatively normal appearing germinal epithelium. Thickening of the tubular walls was noted in half of the cases and slight peritubular fibrosis in one. The Leydig cells were reported as normal or unremarkable.Transmission electron microscopy showed that the thickening of the supporting tissue of the germinal epithelium was caused more by an increase in the thickness of the layers of the lamina propria than of the tubular wall itself. The changes in the basement membrane of the tubular wall consisted mostly of a greater degree of infolding into the tubule and some reduplication which gave rise to a multilayered appearance.

Severe Drooling and Treatment With Botulinum Toxin

2012 ◽  
Vol 21 (1) ◽  
pp. 15-21
Author(s):  
Merete Bakke ◽  
Allan Bardow ◽  
Eigild Møller
Keyword(s):  
Botulinum Toxin ◽  
Side Effects ◽  
Health Risk ◽  
Flow Rate ◽  
Clinical Evidence ◽  
Acetylcholine Release ◽  
Psychosocial Problems ◽  
Rate Reduction ◽  
Local Inhibition ◽  
Surgical Treatments

Severe drooling is associated with discomfort and psychosocial problems and may constitute a health risk. A variety of different surgical and non-surgical treatments have been used to diminish drooling, some of them with little or uncertain effect and others more effective but irreversible or with side effects. Based on clinical evidence, injection with botulinum toxin (BTX) into the parotid and submandibular glands is a useful treatment option, because it is local, reversible, and with few side effects, although it has to be repeated. The mechanism of BTX is a local inhibition of acetylcholine release, which diminishes receptor-coupled secretion and results in a flow rate reduction of 25–50% for 2–7 months.

Sign in / Sign up

Export Citation Format

Share Document