scholarly journals Molecular Tests and Target Therapies in Oncology: recommendations from the Italian workshop

2021 ◽  
Author(s):  
Carmine Pinto ◽  
Mauro Biffoni ◽  
Patrizia Popoli ◽  
Antonio Marchetti ◽  
Paolo Marchetti ◽  
...  
Keyword(s):  
New Technologies ◽  
Opinion Leaders ◽  
Gene Profiling ◽  
Precision Oncology ◽  
Molecular Tests ◽  
Specific Tumor ◽  
Tumor Types ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing ◽  
Tumor Gene

Next-generation sequencing (NGS) and liquid biopsy are new technologies that can allow overall tumor profiling in a single analysis and play an important role in the implementation of precision oncology. However, the lack of guidelines in this setting has limited the development of precision oncology in Italy. This article summarizes recommendations for the appropriate use of NGS in tumor gene profiling, as well as access to tests and target drugs, that were prepared by a group of key opinion leaders and relevant stakeholders. In particular, the need to create laboratory networks capable of carrying out NGS tests in Italy is highlighted. It also appears necessary to establish an adequate reimbursement system for NGS tests. However, the expert panel recommends that the use of NGS tests in clinical practice should be limited to specific tumor types, based on the number and complexity of biomarkers and the availability of treatments.

scholarly journals Analysis of MDM2 Amplification: Next-Generation Sequencing of Patients With Diverse Malignancies

2018 ◽  
pp. 1-14 ◽  
Author(s):  
Shumei Kato ◽  
Jeffrey S. Ross ◽  
Laurie Gay ◽  
Farshid Dayyani ◽  
Jason Roszik ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Mapk Signaling ◽  
Small Subset ◽  
Next Generation ◽  
Investigational Agent ◽  
Mutation Burden ◽  
Tumor Types ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing ◽  
Mdm2 Amplification

Purpose MDM2 amplification can promote tumorigenesis directly or indirectly through p53 inhibition. MDM2 has increasing clinical relevance because inhibitors are under evaluation in clinical trials, and MDM2 amplification is a possible genomic correlate of accelerated progression, known as hyperprogression, after anti–PD-1/PD-L1 immunotherapy. We used next-generation sequencing (NGS) to ascertain MDM2 amplification status across a large number of diverse cancers. Methods We interrogated the molecular profiles of 102,878 patients with diverse malignancies for MDM2 amplification and co-altered genes using clinical-grade NGS (182 to 465 genes). Results MDM2 amplification occurred in 3.5% of patients (3,650 of 102,878). The majority of tumor types had a small subset of patients with MDM2 amplification. Most of these patients (99.0% [3,613/3,650]) had co-alterations that accompanied MDM2 amplification. Various pathways, including those related to tyrosine kinase (37.9% [1,385 of 3,650]), PI3K signaling (25.4% [926 of 3,650]), TP53 (24.9% [910 of 3,650]), and MAPK signaling (23.6% [863 of 3,650]), were involved. Although infrequent, mismatch repair genes and PD-L1 amplification also were co-altered (2.2% [79 of 3,650]). Most patients (97.6% [3,563 of 3,650]) had one or more co-alterations potentially targetable with either a Food and Drug Administration–approved or investigational agent. MDM2 amplifications were less frequently associated with high tumor mutation burden compared with the MDM2 wild-type population (2.9% v 6.5%; P < .001). An illustrative patient who harbored MDM2 amplification and experienced hyperprogression with an immune checkpoint inhibitor is presented. Conclusion MDM2 amplification was found in 3.5% of 102,878 patients, 97.6% of whom harbored genomic co-alterations that were potentially targetable. This study suggests that a small subset of most tumor types have MDM2 amplification as well as pharmacologically tractable co-alterations.

scholarly journals A Canadian guideline on the use of next-generation sequencing in oncology

2019 ◽  
Vol 26 (2) ◽  
Author(s):  
S. Yip ◽  
A. Christofides ◽  
S. Banerji ◽  
M. R. Downes ◽  
I. Izevbaye ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Best Practices ◽  
Sample Selection ◽  
Molecular Profile ◽  
Next Generation ◽  
Canadian Guideline ◽  
Molecular Tests ◽  
Management Guidance ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Rapid advancements in next-generation sequencing (ngs) technology have created an unprecedented opportunity to decipher the molecular profile of tumours to more effectively prevent, diagnose, and treat cancer. Oncologists now have the option to order molecular tests that can guide treatment decisions. However, to date, most oncologists have received limited training in genomics, and they are now faced with the challenge of understanding how such tests and their interpretation align with patient management. Guidance on how to effectively use ngs technology is therefore needed to aid oncologists in applying the results of genomic tests. The Canadian guideline presented here describes best practices and unmet needs related to ngs-based testing for somatic variants in oncology, including clinical application, assay and sample selection, bioinformatics and interpretation of reports performed by laboratories, patient communication, and clinical trials.

scholarly journals Current challenges in the implementation of precision oncology for the management of metastatic colorectal cancer

ESMO Open ◽  
2020 ◽  
Vol 5 (2) ◽  
pp. e000634 ◽  
Author(s):  
Sun Young Kim ◽  
Tae Won Kim
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Precision Oncology ◽  
Controversial Issues ◽  
Considerable Uncertainty ◽  
The Road ◽  
Molecularly Targeted Agents ◽  
On The Road ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Over the last few decades, molecularly targeted agents have been used for the treatment of metastatic colorectal cancer. They have made remarkable contributions to prolonging the lives of patients. The emergence of several biomarkers and their introduction to the clinic have also aided in guiding such treatment. Recently, next-generation sequencing (NGS) has enabled clinicians to identify these biomarkers more easily and reliably. However, there is considerable uncertainty in interpreting and implementing the vast amount of information from NGS. The clinical relevance of biomarkers other than NGS are also subjects of debate. This review covers controversial issues and recent findings on such therapeutics and their molecular targets, including VEGF, EGFR, BRAF, HER2, RAS, actionable fusions, Wnt pathway and microsatellite instability for comprehensive understanding of obstacles on the road to precision oncology in metastatic colorectal cancer.

Precision medicine in oncology – On a journey from dreams to reality

2018 ◽  
Vol 3 (1) ◽  
pp. 15
Author(s):  
Alpa Nimesh Patel ◽  
Mit Shah
Keyword(s):  
Precision Medicine ◽  
Clinical Presentation ◽  
Precision Oncology ◽  
Psychosocial Characteristics ◽  
The Status ◽  
To Come ◽  
The Right ◽  
Next Generation Sequencing Ngs ◽  
Genetic Biomarker ◽  
Generation Sequencing

Precision medicine is defined as treatments targeted to the needs of individual patients on the basis of genetic, biomarker, phenotypic, or psychosocial characteristics that distinguish a given patient from another patient with similar clinical presentation. Precision Oncology is an innovation at the cusp of blooming. We reviewed the status of precision oncology today, and discuss the flaws, mainly in next-generation sequencing (NGS) and the design of clinical trials thus far. Precision oncology although paints a glossy imagery, the reality is laden with inherent flaws, lack of guided research and a generalisability for the clinical market. The scenario in India is similar. It remains to be seen, if Precision Oncology is able to withstand the scrutiny likely to come its way, and if it can appeal largely to a complex socioeconomic market as India. We conclude that precision oncology is not far from an exponential boom, provided the right questions are asked, and answers derived.

scholarly journals Precision Medicine in Pediatric Cancer: Current Applications and Future Prospects

2018 ◽  
Vol 7 (4) ◽  
pp. 39 ◽  
Author(s):  
Atif Ahmed ◽  
Divya Vundamati ◽  
Midhat Farooqi ◽  
Erin Guest
Keyword(s):  
Pediatric Cancer ◽  
Pediatric Population ◽  
Current Status ◽  
Precision Oncology ◽  
Pediatric Tumors ◽  
Future Prospects ◽  
Clinical Scenarios ◽  
The Individual ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Precision oncologic medicine is an emerging approach for cancer treatment that has recently taken giant steps in solid clinical practice. Recent advances in molecular diagnostics that can analyze the individual tumor’s variability in genes have provided greater understanding and additional strategies to treat cancers. Although tumors can be tested by several molecular methods, the use of next-generation sequencing (NGS) has greatly facilitated our understanding of pediatric cancer and identified additional therapeutic opportunities. Pediatric tumors have a different genetic make-up, with a fewer number of actionable targets than adult tumors. Nevertheless, precision oncology in the pediatric population has greatly improved the survival of patients with leukemia and solid tumors. This review discusses the current status of pediatric precision oncology and the different clinical scenarios in which it can be effectively applied.

scholarly journals Pregnancy and Neonatal Outcomes after Transfer of Mosaic Embryos: A Review

2021 ◽  
Vol 10 (7) ◽  
pp. 1369
Author(s):  
Sina Abhari ◽  
Jennifer F. Kawwass
Keyword(s):  
New Technologies ◽  
Multiple Pregnancy ◽  
Chromosome Complement ◽  
Neonatal Outcomes ◽  
Preimplantation Genetic Testing ◽  
Vitro Fertilization ◽  
Mosaic Embryo ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Preimplantation genetic testing for aneuploidy (PGT-A) seeks to identify embryos with a normal chromosome complement during in vitro fertilization (IVF). Transfer of one euploid embryo at a time maximizes the chance of implantation while minimizing the risk of multiple pregnancy. The emergence of new technologies including next generation sequencing (NGS) has led to increased diagnosis of embryonic mosaicism, suggesting the presence of karyotypically distinct cells within a single trophectoderm (TE). Clinical implications of embryonic mosaicism are important in both naturally conceived and IVF pregnancies. Although information regarding outcomes after mosaic embryo transfer (MET) is limited, more than 100 live births have now been documented with rather reassuring outcomes with no abnormal phenotype. Here, we aim to provide a summary of recent data regarding clinical and neonatal outcomes after transfer of mosaic embryos in IVF/PGT-A cycles.

scholarly journals Pharmacogenomics and Pharmacotranscriptomics of Glucocorticoids in Pediatric Acute Lymphoblastic Leukemia

2021 ◽  
Author(s):  
Vladimir Gasic ◽  
Djordje Pavlovic ◽  
Biljana Stankovic ◽  
Nikola Kotur ◽  
Branka Zukic ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Side Effects ◽  
New Technologies ◽  
Lymphoblastic Leukemia ◽  
Glucocorticoid Treatment ◽  
New Knowledge ◽  
Pediatric All ◽  
Next Generation Sequencing Ngs ◽  
Open The Doors ◽  
Generation Sequencing

Pharmacogenomics and pharmacotranscriptomics contribute to more efficient and safer treatment of many diseases, especially malignancies. Acute lymphoblastic leukemia (ALL) is the most common hematological malignancy during childhood. Glucocorticoids, prednisone and dexamethasone, represent the basis of chemotherapy in pediatric ALL. Therapy causes side effects in 75% of patients and 1–3% of pediatric ALL patients die because of therapy side effects rather than the disease itself. Due to this fact, pharmacogenomics and pharmacotranscriptomics have gained key positions in this field. There is a growing knowledge of pharmacogenomics and pharmacotranscriptomics markers relevant for the success of the glucocorticoid treatment of children with ALL. New technologies, such as next-generation sequencing (NGS) have created a possibility for designing panels of pharmacogenomics and pharmacotranscriptomics markers related to the response to glucocorticoid drugs. Optimization of these panels through population pharmacogenomic studies leads to new knowledge that could open the doors widely to pre-emptive pharmacogenomic testing.

Clinical and Technical Aspects of Genomic Diagnostics for Precision Oncology

2017 ◽  
Vol 35 (9) ◽  
pp. 929-933 ◽  
Author(s):  
Yuri Sheikine ◽  
Frank C. Kuo ◽  
Neal I. Lindeman
Keyword(s):  
Genomic Testing ◽  
Precision Oncology ◽  
Strategic Decisions ◽  
Technical Aspects ◽  
Testing Program ◽  
Different Types ◽  
Diagnostic Technology ◽  
Next Generation Sequencing Ngs ◽  
Build Systems ◽  
Generation Sequencing

The emergence of precision medicine has been predicated on significant recent advances in diagnostic technology, particularly the advent of next-generation sequencing (NGS). Although the chemical technology underlying NGS is complex, and the computational biology expertise required to build systems to facilely interpret the results is highly specialized, the variables involved in designing and deploying a genomic testing program for cancer can be readily understood and applied by understanding several basic considerations. In this review, we present key strategic decisions required to optimize a genomic testing program and summarize the technical aspects of different technologies that render those methods more or less suitable for different types of programs.

scholarly journals Next generation sequencing of SARS-CoV-2 genomes: challenges, applications and opportunities

2020 ◽  
Author(s):  
Matteo Chiara ◽  
Anna Maria D’Erchia ◽  
Carmela Gissi ◽  
Caterina Manzari ◽  
Antonio Parisi ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Genomic Sequence ◽  
Molecular Diagnostic ◽  
Next Generation ◽  
Sequencing Data ◽  
Related Data ◽  
Molecular Tests ◽  
Methodological Approaches ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Abstract Various next generation sequencing (NGS) based strategies have been successfully used in the recent past for tracing origins and understanding the evolution of infectious agents, investigating the spread and transmission chains of outbreaks, as well as facilitating the development of effective and rapid molecular diagnostic tests and contributing to the hunt for treatments and vaccines. The ongoing COVID-19 pandemic poses one of the greatest global threats in modern history and has already caused severe social and economic costs. The development of efficient and rapid sequencing methods to reconstruct the genomic sequence of SARS-CoV-2, the etiological agent of COVID-19, has been fundamental for the design of diagnostic molecular tests and to devise effective measures and strategies to mitigate the diffusion of the pandemic. Diverse approaches and sequencing methods can, as testified by the number of available sequences, be applied to SARS-CoV-2 genomes. However, each technology and sequencing approach has its own advantages and limitations. In the current review, we will provide a brief, but hopefully comprehensive, account of currently available platforms and methodological approaches for the sequencing of SARS-CoV-2 genomes. We also present an outline of current repositories and databases that provide access to SARS-CoV-2 genomic data and associated metadata. Finally, we offer general advice and guidelines for the appropriate sharing and deposition of SARS-CoV-2 data and metadata, and suggest that more efficient and standardized integration of current and future SARS-CoV-2-related data would greatly facilitate the struggle against this new pathogen. We hope that our ‘vademecum’ for the production and handling of SARS-CoV-2-related sequencing data, will contribute to this objective.

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