Next-Generation Sequencing and Immunotherapy Biomarkers: A Medical Oncology Perspective

2016 ◽  
Vol 140 (3) ◽  
pp. 245-248 ◽  
Author(s):  
Eric Bernicker
Keyword(s):  
Therapeutic Response ◽  
Medical Oncology ◽  
Checkpoint Inhibitors ◽  
Driver Mutations ◽  
Patient Benefit ◽  
Small Cell Lung ◽  
The Past ◽  
Important Field ◽  
To Come ◽  
Generation Sequencing

The two most important scientific developments of the past decade regarding therapies for patients with non–small cell lung cancer are the ability to exploit particular genetic mutations with targeted therapies and the discovery of drugs that can help the patient's own immune system attack the cancer. Despite these advances, many patients do not yet benefit from either approach. To maximize patient benefit, clinicians and pathologists will need to rationally apply the growing scientific knowledge to best characterize a patient's tumor and possible driver mutations. A growing understanding of host-tumor immune interactions will hopefully help expand our therapeutic options. Lastly, the still elusive identification of immunotherapy biomarkers will hopefully help identify patients most likely to derive a therapeutic response to immune checkpoint inhibitors, and promises to be an important field of study for years to come.

scholarly journals Trends and Developments in Bioinformatics in 2010: Prospects and Perspectives

2011 ◽  
Vol 20 (01) ◽  
pp. 146-155
Author(s):  
A. V. Alekseyenko ◽  
Y. Aphinyanaphongs ◽  
S. Brown ◽  
D. Fenyo ◽  
L. Fu ◽  
...  
Keyword(s):  
Best Practices ◽  
Open Problems ◽  
The Past ◽  
New Methods ◽  
Methods Development ◽  
Long Term Trends ◽  
To Come ◽  
Generation Sequencing

SummaryTo survey major developments and trends in the field of Bioinformatics in 2010 and their relationships to those of previous years, with emphasis on long-term trends, on best practices, on quality of the science of informatics, and on quality of science as a function of informatics.A critical review of articles in the literature of Bioinformatics over the past year.Our main results suggest that Bioinformatics continues to be a major catalyst for progress in Biology and Translational Medicine, as a consequence of new assaying technologies, most predominantly Next Generation Sequencing, which are changing the landscape of modern biological and medical research. These assays critically depend on bioinformatics and have led to quick growth of corresponding informatics methods development. Clinical-grade molecular signatures are proliferating at a rapid rate. However, a highly publicized incident at a prominent university showed that deficiencies in informatics methods can lead to catastrophic consequences for important scientific projects. Developing evidence-driven protocols and best practices is greatly needed given how serious are the implications for the quality of translational and basic science.Several exciting new methods have appeared over the past 18 months, that open new roads for progress in bioinformatics methods and their impact in biomedicine. At the same time, the range of open problems of great significance is extensive, ensuring the vitality of the field for many years to come.

Dynamic relationships among tumor, immune response, and microbiota

2019 ◽  
Vol 3 (1) ◽  
pp. 41
Author(s):  
Takuya Tsunoda ◽  
Kazunori Shimada ◽  
Naoki Uchida ◽  
Shinichi Kobayashi ◽  
Yasutsuna Sasaki
Keyword(s):  
Molecular Mechanisms ◽  
Checkpoint Inhibitors ◽  
Advanced Cancer Patients ◽  
Cancer Treatments ◽  
Disease Etiology ◽  
The Past ◽  
Dynamic Relationships ◽  
The Relationship ◽  
Generation Sequencing

Recently, the analysis of microbiota has been of interest not only for the clarification of the molecular mechanisms of disease etiology, but also the discovery of novel strategies for treatment. Following the development of "next-generation" sequencing, novel areas have been discovered in microbiota; however, in oncology, the relationships between microbiota and cancer have not been fully clarified. In recent literature, surprisingly, detection of gut microbiota in tumor issue itself has been reported. Microbiota might play an important role in carcinogenesis. However, this phenomenon is not well understood, and research in this area has just begun. In the past five years, a paradigm shift has occurred in cancer treatment due to immunotherapy. Immunotherapy has made cure possible even in advanced cancer patients with not only melanoma but also non-small cell lung cancer and others. In this review, we discuss the mechanisms of novel immunotherapies, checkpoint inhibitors, and the relationship between microbiota and immunotherapy. It is of significance to clarify this relationship because it may lead to the discovery of predictive markers for immunotherapy and promote clinical efficacy. Finally, we also mention our activities in the construction of a big database for information on immunotherapy and microbiota, which may lead to excellent possibilities of discovering novel strategies for more effective cancer treatments, and may accelerate the alteration of cancers to the classification of chronic nonfatal disease.

scholarly journals Rapidly changing treatment algorithms for metastatic nonsquamous non-small-cell lung cancer

2018 ◽  
Vol 25 ◽  
pp. 68 ◽  
Author(s):  
B. Melosky
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Checkpoint Inhibitors ◽  
Treatment Algorithm ◽  
Small Cell ◽  
Egfr Mutations ◽  
Driver Mutations ◽  
Small Cell Lung ◽  
Treatment Algorithms

Background The treatment paradigm for metastatic nonsquamous non-small-cell lung cancer (nsclc) continues to change. Algorithms published only 6 months ago are outdated today and are dramatically different from those published a few years ago. New driver mutations continue to be identified, and the development of therapies to inhibit oncogenic addiction is ongoing. Patient survival is improving as treatments become more personalized and effective.Methods This review looks at the outcomes of recent trials and discusses treatment options for patients with metastatic nsclc of nonsquamous histology. Algorithms continue to change quickly, and an attempt is made to keep the paradigm current and applicable into the near future.Results Treatment algorithms for nsclc tumours with EGFR mutations, ALK rearrangements, and ROS1 rearrangements, and for wild-type tumours are presented. A future algorithm based on new immunotherapy data is proposed.Conclusions The treatment algorithm for EGFR mutation is changing with the proven efficacy of osimertinib for the acquired T790M mutation. All patients taking first- or second-generation epidermal growth factor receptor tyrosine kinase inhibitors must be tested. The treatment algorithm for ALK rearrangement has changed with the proven superiority of alectinib compared with crizotinib in the first-line setting. The approval of crizotinib for ROS1 rearrangements now means that patients also must be tested for that mutation. The biomarker for checkpoint inhibitors continues to be PD-L1 by immunohistochemistry stain, but whether testing will be necessary for patient selection if chemotherapy combinations are implemented will be determined soon.

scholarly journals Biomarkers for non-small cell lung cancer immunotherapy

2021 ◽  
Vol 2 (3) ◽  
pp. 31-41
Author(s):  
D. A. Kharagezov ◽  
Yu. N. Lazutin ◽  
E. Yu. Zlatnik ◽  
A. B. Sagakyants ◽  
E. A. Mirzoyan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
T Cell Activation ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Cell Activation ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Driver Mutations ◽  
Small Cell Lung

The discovery of immune checkpoint inhibition has revolutionized the treatment of many solid malignancies, including non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors (ICI) can restore the antitumor immune response by blocking the inhibition of T-cell activation. Anti-programmed death-ligand 1 (PD-L1) is currently the main biomarker of the effectiveness of anti-PD-1 / PD-L1 blockade in the treatment of NSCLC without driver mutations. High tumor mutational burden suggests an increased neoantigens load and has been associated with the effectiveness of ICI therapy. Microsatellite instability, a biomarker approved for immunotherapy across solid tumors, but it is uncommon in NSCLC. Primary resistance to ICIsis characteristic of NSCLC with driver mutations, acquired is associated with immunoediting resulting in the depletion of potentially immunogenic neoantigens. The review discusses recent advances and future directions for predicting the results of immunotherapy in patients with NSCLC.

scholarly journals Dynamic relationships among tumor, immune response, and microbiota

2017 ◽  
Vol 1 (2) ◽  
Author(s):  
Takuya Tsunoda ◽  
Kazunori Shimada ◽  
Naoki Uchida ◽  
Shinichi Kobayashi ◽  
Yasutsuna Sasaki
Keyword(s):  
Molecular Mechanisms ◽  
Checkpoint Inhibitors ◽  
Advanced Cancer Patients ◽  
Cancer Treatments ◽  
Disease Etiology ◽  
The Past ◽  
Dynamic Relationships ◽  
The Relationship ◽  
Generation Sequencing

Recently, the analysis of microbiota has been of interest not only for the clarification of the molecular mechanisms of disease etiology, but also the discovery of novel strategies for treatment. Following the development of “next-generation” sequencing, novel areas have been discovered in microbiota; however, in oncology, the relationships between microbiota and cancer have not been fully clarified. In recent literature, surprisingly, detection of gut microbiota in tumor issue itself has been reported. Microbiota might play an important role in carcinogenesis. However, this phenomenon is not well understood, and research in this area has just begun. In the past five years, a paradigm shift has occurred in cancer treatment due to immunotherapy. Immunotherapy has made cure possible even in advanced cancer patients with not only melanoma but also non-small cell lung cancer and others. In this review, we discuss the mechanisms of novel immunotherapies, checkpoint inhibitors, and the relationship between microbiota and immunotherapy. It is of significance to clarify this relationship because it may lead to the discovery of predictive markers for immunotherapy and promote clinical efficacy. Finally, we also mention our activities in the construction of a big database for information on immunotherapy and microbiota, which may lead to excellent possibilities of discovering novel strategies for more effective cancer treatments, and may accelerate the alteration of cancers to the classification of chronic nonfatal disease.

scholarly journals Treating KRAS-mutant NSCLC: latest evidence and clinical consequences

2017 ◽  
Vol 9 (9) ◽  
pp. 589-597 ◽  
Author(s):  
Pilar Garrido ◽  
María Eugenia Olmedo ◽  
Ana Gómez ◽  
Luis Paz Ares ◽  
Fernando López-Ríos ◽  
...  
Keyword(s):  
Small Molecules ◽  
Checkpoint Inhibitors ◽  
Driver Mutations ◽  
Small Cell Lung ◽  
Kras Mutations ◽  
Mutation Status ◽  
Comprehensive Genomic Profiling ◽  
Clinical Consequences ◽  
Oncogenic Driver ◽  
Prognostic Implications

KRAS mutations represent one of the most prevalent oncogenic driver mutations in non-small cell lung cancer (NSCLC). For many years we have unsuccessfully addressed KRAS mutation as a unique disease. The recent widespread use of comprehensive genomic profiling has identified different subgroups with prognostic implications. Moreover, recent data recognizing the distinct biology and therapeutic vulnerabilities of different KRAS subgroups have allowed us to explore different treatment approaches. Small molecules that selectively inhibit KRAS G12C or use of immune checkpoint inhibitors based on co-mutation status are some examples which anticipate that personalized treatment for this challenging disease is finally on the horizon.

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