scholarly journals CancerTracer: a curated database for intrapatient tumor heterogeneity

2019 ◽  
Author(s):  
Chen Wang ◽  
Jian Yang ◽  
Hong Luo ◽  
Kun Wang ◽  
Yu Wang ◽  
...  
Keyword(s):  
Phylogenetic Trees ◽  
Predictive Biomarkers ◽  
Patient Specific ◽  
Intratumor Heterogeneity ◽  
Cancer Therapies ◽  
Specific Tumor ◽  
Multiple Biopsies ◽  
Evolutionary Trajectories ◽  
Personalized Cancer ◽  
Clonal Composition

Abstract Comprehensive genomic analyses of cancers have revealed substantial intrapatient molecular heterogeneities that may explain some instances of drug resistance and treatment failures. Examination of the clonal composition of an individual tumor and its evolution through disease progression and treatment may enable identification of precise therapeutic targets for drug design. Multi-region and single-cell sequencing are powerful tools that can be used to capture intratumor heterogeneity. Here, we present a database we’ve named CancerTracer (http://cailab.labshare.cn/cancertracer): a manually curated database designed to track and characterize the evolutionary trajectories of tumor growth in individual patients. We collected over 6000 tumor samples from 1548 patients corresponding to 45 different types of cancer. Patient-specific tumor phylogenetic trees were constructed based on somatic mutations or copy number alterations identified in multiple biopsies. Using the structured heterogeneity data, researchers can identify common driver events shared by all tumor regions, and the heterogeneous somatic events present in different regions of a tumor of interest. The database can also be used to investigate the phylogenetic relationships between primary and metastatic tumors. It is our hope that CancerTracer will significantly improve our understanding of the evolutionary histories of tumors, and may facilitate the identification of predictive biomarkers for personalized cancer therapies.

scholarly journals The Personalized Cancer Network Explorer (PeCaX) as a visual analytics tool to support molecular tumor boards

2021 ◽  
Author(s):  
Mirjam Figaschewski ◽  
Bilge Sürün ◽  
Thorsten Tiede ◽  
Oliver Kohlbacher
Keyword(s):  
Biological Networks ◽  
Visual Analytics ◽  
Patient Specific ◽  
Visual Interpretation ◽  
Web Based ◽  
Specific Tumor ◽  
Tumor Boards ◽  
Personalized Oncology ◽  
Personalized Cancer ◽  
Cancer Network

Personalized oncology represents a shift in cancer treatment from conventional methods to target specific therapies where the decisions are made based on the patient specific tumor profile. Selection of the optimal therapy relies on a complex interdisciplinary analysis and interpretation of these variants by experts in molecular tumor boards. With up to hundreds of somatic variants identified in a tumor, this process requires visual analytics tools to guide and accelerate the annotation process. The Personal Cancer Network Explorer (PeCaX) is a visual analytics tool supporting the efficient annotation, navigation, and interpretation of somatic genomic variants through functional annotation, drug target annotation, and visual interpretation within the context of biological networks. Starting with somatic variants in a VCF file, PeCaX enables users to explore these variants through a web-based graphical user interface. The most protruding feature of PeCaX is the combination of clinical variant annotation and gene- drug networks with an interactive visualization. This reduces the time and effort the user needs to invest to get to a treatment suggestion and helps to generate new hypotheses. PeCaX is being provided as a platform-independent containerized software package for local or institution-wide deployment. PeCaX is available for download at https://github.com/KohlbacherLab/PeCaX-docker.

scholarly journals Use of Circulating Tumour DNA (ctDNA) for Measurement of Therapy Predictive Biomarkers in Patients with Cancer

2022 ◽  
Vol 12 (1) ◽  
pp. 99
Author(s):  
Michael J. Duffy ◽  
John Crown
Keyword(s):  
Gold Standard ◽  
Kinase Inhibitors ◽  
Predictive Biomarkers ◽  
Lower Sensitivity ◽  
Cancer Therapies ◽  
Gold Standard Method ◽  
Biomarker Analysis ◽  
Egfr Tyrosine Kinase Inhibitors ◽  
Biomarker Testing ◽  
Circulating Tumour Dna

Biomarkers that predict likely response or resistance to specific therapies are critical in personalising treatment for cancer patients. Such biomarkers are now available for an increasing number of anti-cancer therapies, especially targeted therapy and immunotherapy. The gold-standard method for determining predictive biomarkers requires tumour tissue. Obtaining tissue, however, is not always possible and even if possible, the amount or quality of tissue obtained may be inadequate for biomarker analysis. Tumour DNA, however, can be released into the bloodstream, giving rise to what is referred to as circulating tumour DNA (ctDNA). In contrast to tissue, blood can be obtained from effectively all patients in a minimally invasive and safe manner. Other advantages of blood over tissue for biomarker testing include a shorter turn-around time and an ability to perform serial measurements. Furthermore, blood should provide a more complete profile of mutations present in heterogeneous tumours than a single-needle tissue biopsy. A limitation of blood vis-à-vis tissue, however, is lower sensitivity and, thus, the possibility of missing an actionable mutation. Despite this limitation, blood-based predictive biomarkers, such as mutant EGFR for predicting response to EGFR tyrosine kinase inhibitors in advanced non-small-cell lung cancer and mutant PIK3CA for predicting response to alpelisib in combination with fulvestrant in advanced breast cancer, may be used when tissue is unavailable. Although tissue remains the gold standard for detecting predictive biomarkers, it is likely that several further blood-based assays will soon be validated and used when tissue is unavailable or unsuitable for analysis.

scholarly journals Evolutionary Highways to Persistent Bacterial Infection

2018 ◽  
Author(s):  
Jennifer A Bartell ◽  
Lea M Sommer ◽  
Janus A J Haagensen ◽  
Anne Loch ◽  
Rocio Espinosa ◽  
...  
Keyword(s):  
Complex Trait ◽  
Host Finding ◽  
Patient Specific ◽  
Rapid Adaptation ◽  
Multiple Traits ◽  
New Associations ◽  
Persistent Infections ◽  
Evolutionary Trajectories ◽  
Pathoadaptive Mutations ◽  
Trait Correlations

ABSTRACTPersistent infections require bacteria to evolve from their naïve colonization state by optimizing fitness in the host. This optimization involves coordinated adaptation of multiple traits, obscuring evolutionary trends and complicating infection management. Accordingly, we screen 8 infection-relevant phenotypes of 443 longitudinal Pseudomonas aeruginosa isolates from 39 young cystic fibrosis patients over 10 years. Using statistical modeling, we map evolutionary trajectories and identify trait correlations accounting for patient-specific influences. By integrating previous genetic analyses of 474 isolates, we provide a window into early adaptation to the host, finding: 1) a 2-3 year timeline of rapid adaptation after colonization, 2) variant “naïve” and “adapted” states reflecting discordance between phenotypic and genetic adaptation, 3) adaptive trajectories leading to persistent infection via 3 distinct evolutionary modes, and 4) new associations between phenotypes and pathoadaptive mutations. Ultimately, we effectively deconvolute complex trait adaptation, offering a framework for evolutionary studies and precision medicine in clinical microbiology.

Premedications for Cancer Therapies: A Primer for the Hematology/Oncology Provider

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Amber Clemmons, PharmD, BCOP ◽  
Arpita Gandhi, PharmD, BCOP ◽  
Andrea Clarke, PharmD ◽  
Sarah Jimenez, APN-BC, AGACNP, AOCNP ◽  
Thuy Le, MD ◽  
...  
Keyword(s):  
Best Practices ◽  
Adverse Events ◽  
Chemotherapeutic Agents ◽  
Patient Specific ◽  
Cancer Therapies ◽  
Quality Of Data ◽  
Advanced Practitioner ◽  
Patients At Risk ◽  
Radiation Induced

Chemotherapeutic agents and radiation therapy are associated with numerous potential adverse events (AEs). Many of these common AEs, namely chemotherapy- or radiation-induced nausea and vomiting, hypersensitivity reactions, and edema, can lead to deleterious outcomes (such as treatment nonadherence or cessation, or poor clinical outcomes) if not prevented appropriately. The occurrence and severity of these AEs can be prevented with the correct prescribing of prophylactic medications, often called “premedications.” The advanced practitioner in hematology/oncology should have a good understanding of which chemotherapeutic agents are known to place patients at risk for these adverse events as well as be able to determine appropriate prophylactic medications to employ in the prevention of these adverse events. While several guidelines and literature exist regarding best practices for prophylaxis strategies, differences among guidelines and quality of data should be explored in order to accurately implement patient-specific recommendations. Herein, we review the existing literature for prophylaxis and summarize best practices.

scholarly journals Alternative splicing in endothelial cells: novel therapeutic opportunities in cancer angiogenesis

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Anna Di Matteo ◽  
Elisa Belloni ◽  
Davide Pradella ◽  
Ambra Cappelletto ◽  
Nina Volf ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Human Cancer ◽  
Single Gene ◽  
Predictive Biomarkers ◽  
Protein Isoforms ◽  
Therapeutic Interventions ◽  
Cancer Therapies ◽  
Functional Changes ◽  
Splicing Regulators ◽  
Multiple Protein

AbstractAlternative splicing (AS) is a pervasive molecular process generating multiple protein isoforms, from a single gene. It plays fundamental roles during development, differentiation and maintenance of tissue homeostasis, while aberrant AS is considered a hallmark of multiple diseases, including cancer. Cancer-restricted AS isoforms represent either predictive biomarkers for diagnosis/prognosis or targets for anti-cancer therapies. Here, we discuss the contribution of AS regulation in cancer angiogenesis, a complex process supporting disease development and progression. We consider AS programs acting in a specific and non-redundant manner to influence morphological and functional changes involved in cancer angiogenesis. In particular, we describe relevant AS variants or splicing regulators controlling either secreted or membrane-bound angiogenic factors, which may represent attractive targets for therapeutic interventions in human cancer.

Professionalism in Global, Personalized Cancer Care: Restoring Authenticity and Integrity

2013 ◽  
pp. 152-156
Author(s):  
Antonella Surbone
Keyword(s):  
Moral Education ◽  
Cancer Care ◽  
Conflicts Of Interest ◽  
Global Scale ◽  
Cancer Therapies ◽  
Global Issues ◽  
Body Of Knowledge ◽  
New Cancer Therapies ◽  
Correct Application ◽  
Personalized Cancer

Personalized medicine is revolutionizing cancer care and creating new expectations among oncologists and patients. At present the benefit is still marginal, however, and must be understood as incremental. In addition, cultural and resource disparities limit the sustainability of new cancer therapies on a global scale. Adequate instruments are needed to enable our exercise of sound and honest judgment in distinguishing breakthrough treatments from those that yield only marginal or doubtful improvements, and to develop strategies for formulation and correct application of balanced guidelines for sustainable cancer care. Professionalism requires that the acquisition of knowledge and skills go hand in hand with moral education in the intellectual virtues of humility, perseverance, adaptability, communicativeness, and commitment to resist self-deception or conflicts of interest. Hidden curricula undermine the moral values of medicine: these must be understood and uncovered. We should possess a special body of knowledge, skills, and values that allow us to change our practices when appropriate and to be stewards of society's limited resources through proper communication with our patients and families. In the era of personalized oncology and global issues of sustainability, professional authenticity and integrity in cancer clinical practice are key to bridging the gaps between true and false expectations of patients and the public.

scholarly journals ctDNA monitoring using patient-specific sequencing and integration of variant reads

2020 ◽  
Vol 12 (548) ◽  
pp. eaaz8084 ◽  
Author(s):  
Jonathan C. M. Wan ◽  
Katrin Heider ◽  
Davina Gale ◽  
Suzanne Murphy ◽  
Eyal Fisher ◽  
...  
Keyword(s):  
Residual Disease ◽  
Early Stage ◽  
Area Under The Curve ◽  
Patient Specific ◽  
Sequencing Data ◽  
Liquid Biopsies ◽  
Whole Exome ◽  
Mutation Burden ◽  
Median Area ◽  
Personalized Cancer

Circulating tumor-derived DNA (ctDNA) can be used to monitor cancer dynamics noninvasively. Detection of ctDNA can be challenging in patients with low-volume or residual disease, where plasma contains very few tumor-derived DNA fragments. We show that sensitivity for ctDNA detection in plasma can be improved by analyzing hundreds to thousands of mutations that are first identified by tumor genotyping. We describe the INtegration of VAriant Reads (INVAR) pipeline, which combines custom error-suppression methods and signal-enrichment approaches based on biological features of ctDNA. With this approach, the detection limit in each sample can be estimated independently based on the number of informative reads sequenced across multiple patient-specific loci. We applied INVAR to custom hybrid-capture sequencing data from 176 plasma samples from 105 patients with melanoma, lung, renal, glioma, and breast cancer across both early and advanced disease. By integrating signal across a median of >105 informative reads, ctDNA was routinely quantified to 1 mutant molecule per 100,000, and in some cases with high tumor mutation burden and/or plasma input material, to parts per million. This resulted in median area under the curve (AUC) values of 0.98 in advanced cancers and 0.80 in early-stage and challenging settings for ctDNA detection. We generalized this method to whole-exome and whole-genome sequencing, showing that INVAR may be applied without requiring personalized sequencing panels so long as a tumor mutation list is available. As tumor sequencing becomes increasingly performed, such methods for personalized cancer monitoring may enhance the sensitivity of cancer liquid biopsies.

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