Functional precision oncology: Testing tumors with drugs to identify vulnerabilities and novel combinations DOI Creative Commons
Anthony Letai, Patrick Bhola, Alana L. Welm

и другие.

Cancer Cell, Год журнала: 2021, Номер 40(1), С. 26 - 35

Опубликована: Дек. 23, 2021

Functional precision medicine is a strategy whereby live tumor cells from affected individuals are directly perturbed with drugs to provide immediately translatable, personalized information guide therapy. The heterogeneity of human cancer has led the realization that approaches needed improve treatment outcomes. Precision oncology traditionally used static features dictate which therapies should be used. Static can include expression key targets or genomic analysis mutations identify therapeutically targetable "drivers." Although surprisingly small proportion derive clinical benefit approach, functional additional regarding vulnerabilities. We discuss emerging technologies for as well limitations and challenges in using these assays trials will necessary determine whether outcomes eventually become standard tool oncology.

Язык: Английский

Defining Driver DNA Methylation Changes in Human Cancer DOI Open Access
Gerd P. Pfeifer

International Journal of Molecular Sciences, Год журнала: 2018, Номер 19(4), С. 1166 - 1166

Опубликована: Апрель 12, 2018

Human malignant tumors are characterized by pervasive changes in the patterns of DNA methylation. These include a globally hypomethylated tumor cell genome and focal hypermethylation numerous 5′-cytosine-phosphate-guanine-3′ (CpG) islands, many them associated with gene promoters. It has been challenging to link specific methylation tumorigenesis cause-and-effect relationship. Some evidence suggests that cancer-associated hypomethylation may increase genomic instability. Promoter events can lead silencing genes functioning pathways reflecting hallmarks cancer, including repair, cycle regulation, promotion apoptosis or control key tumor-relevant signaling networks. A convincing argument for tumor-driving role be made when same also frequently mutated cancer. Many most commonly hypermethylated encode developmental transcription factors, which permanent silencing. Inactivation such will deprive cells initiate from option undergoing maintaining lineage differentiation lock into perpetuated stem cell-like state thus providing an additional window transformation.

Язык: Английский

Процитировано

278

DNA Methylation Reprogramming during Mammalian Development DOI Open Access
Yang Zeng, Taiping Chen

Genes, Год журнала: 2019, Номер 10(4), С. 257 - 257

Опубликована: Март 29, 2019

DNA methylation (5-methylcytosine, 5mC) is a major form of modification in the mammalian genome that plays critical roles chromatin structure and gene expression. In general, stably maintained somatic tissues. However, patterns levels show dynamic changes during development. Specifically, undergoes two waves global demethylation remethylation for purpose producing next generation. The first wave occurs germline, initiated with erasure primordial germ cells (PGCs) completed establishment sex-specific later stages cell second after fertilization, including most marks inherited from gametes subsequent embryonic pattern. reprogramming involve both distinct shared mechanisms. this review article, we provide an overview key events, focusing on important players these processes, methyltransferases (DNMTs) ten-eleven translocation (TET) family 5mC dioxygenases.

Язык: Английский

Процитировано

275

Non-invasive diagnosis of early-stage lung cancer using high-throughput targeted DNA methylation sequencing of circulating tumor DNA (ctDNA) DOI Creative Commons
Wenhua Liang, Yue Zhao, Weizhe Huang

и другие.

Theranostics, Год журнала: 2019, Номер 9(7), С. 2056 - 2070

Опубликована: Янв. 1, 2019

Rational: LDCT screening can identify early-stage lung cancers yet introduces excessive false positives and it remains a great challenge to differentiate malignant tumors from benign solitary pulmonary nodules, which calls for better non-invasive diagnostic tools.Methods: We performed DNA methylation profiling by high throughput bisulfite sequencing in tissue samples (nodule size < 3 cm diameter) learn patterns that cancerous lesions.Then we filtered out exhibiting background circulating tumor (ctDNA) built an assay plasma sample classification.Results: first of 230 cancer-specific achieved sensitivity 92.7% (88.3% -97.1%) specificity 92.8% (89.3% -96.3%).These tissue-derived markers were further using training set 66 9 selected build prediction model.From independent validation additional samples, this model obtained 79.5% (63.5% -90.7%) 85.2% (66.3% -95.8%) differentiating patients with (n = 39) lesions 27).Additionally, when tested on gender age matched asymptomatic normal individuals 118), our 93.2% (89.0%-98.3%).Specifically, is highly sensitive towards cancer, 75.0%(55.0%-90.0%) 20 stage Ia cancer 85.7% (57.1%-100.0%) 7 Ib patients. Conclusions:We have developed novel blood based detecting early as well nodules.

Язык: Английский

Процитировано

210

Large-Scale Topological Changes Restrain Malignant Progression in Colorectal Cancer DOI Creative Commons

Sarah E. Johnstone,

Alejandro Reyes, Yifeng Qi

и другие.

Cell, Год журнала: 2020, Номер 182(6), С. 1474 - 1489.e23

Опубликована: Авг. 24, 2020

Язык: Английский

Процитировано

191

Functional precision oncology: Testing tumors with drugs to identify vulnerabilities and novel combinations DOI Creative Commons
Anthony Letai, Patrick Bhola, Alana L. Welm

и другие.

Cancer Cell, Год журнала: 2021, Номер 40(1), С. 26 - 35

Опубликована: Дек. 23, 2021

Functional precision medicine is a strategy whereby live tumor cells from affected individuals are directly perturbed with drugs to provide immediately translatable, personalized information guide therapy. The heterogeneity of human cancer has led the realization that approaches needed improve treatment outcomes. Precision oncology traditionally used static features dictate which therapies should be used. Static can include expression key targets or genomic analysis mutations identify therapeutically targetable "drivers." Although surprisingly small proportion derive clinical benefit approach, functional additional regarding vulnerabilities. We discuss emerging technologies for as well limitations and challenges in using these assays trials will necessary determine whether outcomes eventually become standard tool oncology.

Язык: Английский

Процитировано

188