scholarly journals Detecting Resistance to Therapeutic ALK Inhibitors in Tumor Tissue and Liquid Biopsy Markers: An Update to a Clinical Routine Practice

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 168
Author(s):  
Paul Hofman
Keyword(s):  
Tumor Tissue ◽  
Tumor Response ◽  
Routine Practice ◽  
Mechanisms Of Resistance ◽  
Liquid Biopsies ◽  
Genomic Alterations ◽  
Alk Inhibitors ◽  
Initial Tumor ◽  
Biological Sampling

The survival of most patients with advanced stage non-small cell lung cancer is prolonged by several months when they are treated with first- and next-generation inhibitors targeting ALK rearrangements, but resistance inevitably emerges. Some of the mechanisms of resistance are sensitive to novel ALK inhibitors but after an initial tumor response, more or less long-term resistance sets in. Therefore, to adapt treatment it is necessary to repeat biological sampling over time to look for different mechanisms of resistance. To this aim it is essential to obtain liquid and/or tissue biopsies to detect therapeutic targets, in particular for the analysis of different genomic alterations. This review discusses the mechanisms of resistance to therapeutics targeting genomic alterations in ALK as well as the advantages and the limitations of liquid biopsies for their identification.

scholarly journals MA 07.06 Detection of Mechanisms of Resistance to ALK Inhibitors in Routine Practice: A Retrospective Study

2017 ◽  
Vol 12 (11) ◽  
pp. S1828
Author(s):  
P. Jamme ◽  
C. Descarpentries ◽  
M. Wislez ◽  
E. Dansin ◽  
V. Grégoire ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Routine Practice ◽  
Mechanisms Of Resistance ◽  
Alk Inhibitors

scholarly journals Relevance of Detection of Mechanisms of Resistance to ALK Inhibitors in ALK-Rearranged NSCLC in Routine Practice

2019 ◽  
Vol 20 (4) ◽  
pp. 297-304.e1 ◽  
Author(s):  
Philippe Jamme ◽  
Clotilde Descarpentries ◽  
Radj Gervais ◽  
Eric Dansin ◽  
Marie Wislez ◽  
...  
Keyword(s):  
Routine Practice ◽  
Mechanisms Of Resistance ◽  
Alk Inhibitors

scholarly journals Liquid Biopsies: Genotyping Circulating Tumor DNA

2014 ◽  
Vol 32 (6) ◽  
pp. 579-586 ◽  
Author(s):  
Luis A. Diaz ◽  
Alberto Bardelli
Keyword(s):  
Tumor Heterogeneity ◽  
Dna Analysis ◽  
Tumor Tissue ◽  
Tumor Staging ◽  
Circulating Tumor Dna ◽  
Genetic Alterations ◽  
Routine Practice ◽  
Liquid Biopsies ◽  
Tumor Dna ◽  
Single Snapshot

Genotyping tumor tissue in search of somatic genetic alterations for actionable information has become routine practice in clinical oncology. Although these sequence alterations are highly informative, sampling tumor tissue has significant inherent limitations; tumor tissue is a single snapshot in time, is subject to selection bias resulting from tumor heterogeneity, and can be difficult to obtain. Cell-free fragments of DNA are shed into the bloodstream by cells undergoing apoptosis or necrosis, and the load of circulating cell-free DNA (cfDNA) correlates with tumor staging and prognosis. Moreover, recent advances in the sensitivity and accuracy of DNA analysis have allowed for genotyping of cfDNA for somatic genomic alterations found in tumors. The ability to detect and quantify tumor mutations has proven effective in tracking tumor dynamics in real time as well as serving as a liquid biopsy that can be used for a variety of clinical and investigational applications not previously possible.

Feasibility barriers and effectiveness of specific treatments for early psychosis in routine mental health care

2011 ◽  
Vol 26 (S2) ◽  
pp. 2042-2042
Author(s):  
M. Ruggeri
Keyword(s):  
Psychosocial Interventions ◽  
Early Psychosis ◽  
Control Group ◽  
Routine Practice ◽  
Evidence Based ◽  
Roles And Responsibilities ◽  
Or Practice ◽  
Representative Samples ◽  
Poor Management

IntroductionIssues of organisational structure and commitment, resource development, and clarity of roles and responsibilities must be addressed before proceeding with any attempt to implement evidence based interventions in a specific service.Evidence suggests that the management of most mental disorders and especially of psychoses is frequently suboptimal. This trend might reflect instances of inadequate resource allocation, but might also reflect the effects of stigma, discrimination, and social exclusion that people with psychosis often experience. It might also indicate poor management of available resources or deficiencies in knowledge or practice.AimsMulti-element psychosocial interventions in the first 5 years from psychosis onset have proved to facilitating recovery and reducing long-term disability. However, most studies often do not test efficacy against a control group and have been conducted in non-epidemiologically representative samples. The presentation will be focussed on process of assessment of acceptability and discrepancies between evidence and clinical practice in the treatment of schizophrenia in community care.Methods and ResultsTrials - such as the GET UP Trial (National Coordinator: Mirella Ruggeri) that is part of the Strategic Research Programs of the Italian Government - that are being conducted in the routine practice and that aim to test the feasibility and cost-effectiveness of evidence-based psychosocial interventions will be presented and discussed.ConclusionsVerify the barriers to application and situations when evidence-based interventions practice might be ineffective or inappropriate, understanding their advantages and limitations is a crucial challenge in the area of early psychosis treatment.

Lymphoscintigraphy in clinical routine practice: Reproducibility and accuracy in melanoma patients with a long-term follow-up

2014 ◽  
Vol 40 (1) ◽  
pp. 55-60 ◽  
Author(s):  
G.C. Vitali ◽  
G. Trifirò ◽  
M. Zonta ◽  
E. Pennacchioli ◽  
L. Santoro ◽  
...  
Keyword(s):  
Routine Practice ◽  
Clinical Routine ◽  
Long Term Follow Up ◽  
Melanoma Patients

Cell-Free DNA Detection of Tumor Mutations in Heterogeneous, Localized Prostate Cancer Via Targeted, Multiregion Sequencing

2021 ◽  
pp. 710-725
Author(s):  
Emmalyn Chen ◽  
Clinton L. Cario ◽  
Lancelote Leong ◽  
Karen Lopez ◽  
César P. Márquez ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Tissue ◽  
Somatic Tissue ◽  
Localized Prostate Cancer ◽  
Genomic Alterations ◽  
Cell Free Dna ◽  
Free Dna ◽  
Multiple Regions ◽  
Localized Disease ◽  
Tissue Alterations

PURPOSE Cell-free DNA (cfDNA) may allow for minimally invasive identification of biologically relevant genomic alterations and genetically distinct tumor subclones. Although existing biomarkers may detect localized prostate cancer, additional strategies interrogating genomic heterogeneity are necessary for identifying and monitoring aggressive disease. In this study, we aimed to evaluate whether circulating tumor DNA can detect genomic alterations present in multiple regions of localized prostate tumor tissue. METHODS Low-pass whole-genome and targeted sequencing with a machine-learning guided 2.5-Mb targeted panel were used to identify single nucleotide variants, small insertions and deletions (indels), and copy-number alterations in cfDNA. The majority of this study focuses on the subset of 21 patients with localized disease, although 45 total individuals were evaluated, including 15 healthy controls and nine men with metastatic castration-resistant prostate cancer. Plasma cfDNA was barcoded with duplex unique molecular identifiers. For localized cases, matched tumor tissue was collected from multiple regions (one to nine samples per patient) for comparison. RESULTS Somatic tumor variants present in heterogeneous tumor foci from patients with localized disease were detected in cfDNA, and cfDNA mutational burden was found to track with disease severity. Somatic tissue alterations were identified in cfDNA, including nonsynonymous variants in FOXA1, PTEN, MED12, and ATM. Detection of these overlapping variants was associated with seminal vesicle invasion ( P = .019) and with the number of variants initially found in the matched tumor tissue samples ( P = .0005). CONCLUSION Our findings demonstrate the potential of targeted cfDNA sequencing to detect somatic tissue alterations in heterogeneous, localized prostate cancer, especially in a setting where matched tumor tissue may be unavailable (ie, active surveillance or treatment monitoring).

The crystal arthropathies

2013 ◽  
Vol 6 (11) ◽  
pp. 681-687 ◽  
Author(s):  
Robert A Jones ◽  
Brian Quilty
Keyword(s):  
Quality Of Life ◽  
Risk Factors ◽  
Inflammatory Arthritis ◽  
Term Treatment ◽  
Routine Practice ◽  
Treatment Goals ◽  
Crystal Arthropathies ◽  
Long Term Treatment

Unlike many other forms of inflammatory arthritis, the crystal arthropathies are routinely diagnosed and managed in primary care. Gout, in particular, is relatively commonplace and rates of other types of crystal-related arthritis are predicted to increase. These are, therefore, conditions that GPs and trainees will regularly encounter during routine practice. While the clinical features and pathophysiology of gout and pseudo-gout are well described, the long-term treatment goals and options of management are often less well understood, and opportunities to assess for associated co-morbidities can easily be missed. GPs can be central in optimising management by promptly and appropriately addressing acute symptoms, preventing recurrent attacks, minimising disability and work absences, reducing cardiovascular risk factors, improving general health and enhancing quality of life.

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