Browse
Submit Data
Databases
API
Help

Dataset Information

11 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The Role Of Circulating Tumor DNA In Therapeutic Resistance.

ABSTRACT: The application of precision medicine in cancer treatment has partly succeeded in reducing the side effects of unnecessary chemotherapeutics and in improving the survival rate of patients. However, with the long-term use of therapy, the dynamically changing intratumoral and intertumoral heterogeneity eventually gives rise to therapeutic resistance. In recent years, a novel testing technology (termed liquid biopsy) using circulating tumor DNAs (ctDNAs) extracted from peripheral blood samples from patients with cancer has brought about new expectations to the medical community. Using ctDNAs, clinicians can trace the heterogeneity pattern to duly adjust individual therapy and prolong overall survival for patients with cancer. Technological advances in detecting and characterizing ctDNAs (eg, development of next-generation sequencing) have provided clinicians with a valuable tool for genotyping tumors individually and identifying genetic and epigenetic alterations of the entire tumor to capture mutations associated with therapeutic resistance.

SUBMITTER: Xu C

PROVIDER: S-EPMC6850686 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

The Role Of Circulating Tumor DNA In Therapeutic Resistance.

Xu Chenxin C Cao Haixia H Shi Chen C Feng Jifeng J

OncoTargets and therapy 20191108

The application of precision medicine in cancer treatment has partly succeeded in reducing the side effects of unnecessary chemotherapeutics and in improving the survival rate of patients. However, with the long-term use of therapy, the dynamically changing intratumoral and intertumoral heterogeneity eventually gives rise to therapeutic resistance. In recent years, a novel testing technology (termed liquid biopsy) using circulating tumor DNAs (ctDNAs) extracted from peripheral blood samples from ...[more]

PMID: 31807023

Similar Datasets

Monitoring Therapeutic Response and Resistance: Analysis of Circulating Tumor DNA in Patients With ALK+ Lung Cancer.

Project description:IntroductionDespite initial effectiveness of ALK receptor tyrosine kinase inhibitors (TKIs) in patients with ALK+ NSCLC, therapeutic resistance will ultimately develop. Serial tracking of genetic alterations detected in circulating tumor DNA (ctDNA) can be an informative strategy to identify response and resistance. This study evaluated the utility of analyzing ctDNA as a function of response to ensartinib, a potent second-generation ALK TKI.MethodsPre-treatment plasma was collected from 76 patients with ALK+ NSCLC who were ALK TKI-naive or had received prior ALK TKI, and analyzed for specific genetic alterations. Longitudinal plasma samples were analyzed from a subset (n = 11) of patients. Analysis of pre-treatment tumor biopsy specimens from 22 patients was compared with plasma.ResultsDisease-associated genetic alterations were detected in 74% (56 of 76) of patients, the most common being EML4-ALK. Concordance of ALK fusion between plasma and tissue was 91% (20 of 22 blood and tissue samples). Twenty-four ALK kinase domain mutations were detected in 15 patients, all had previously received an ALK TKI; G1269A was the most prevalent (4 of 24). Patients with a detectable EML4-ALK variant 1 (V1) fusion had improved response (9 of 17 patients; 53%) to ensartinib compared to patients with EML4-ALK V3 fusion (one of seven patients; 14%). Serial changes in ALK alterations were observed during therapy.ConclusionsClinical utility of ctDNA was shown, both at pre-treatment by identifying a potential subgroup of ALK+ NSCLC patients who may derive more benefit from ensartinib and longitudinally by tracking resistance. Prospective application of this technology may translate to improved outcomes for NSCLC patients treated with ALK TKIs.

| S-EPMC6823161 | biostudies-literature

Circulating tumor DNA predicts therapeutic outcome in mantle cell lymphoma.

Project description:Mantle cell lymphoma (MCL) is biologically and clinically heterogeneous and would benefit from prognostic biomarkers to guide management. Circulating tumor DNA (ctDNA) is a novel prognostic biomarker in diffuse large B-cell lymphoma that may have applicability in MCL. We analyzed ctDNA dynamics in previously untreated patients with MCL who received induction therapy with bortezomib and DA-EPOCH-R for 6 cycles followed by random assignment to observation or bortezomib maintenance in responding patients in a prospective phase 2 study. Most patients also underwent initial treatment window of bortezomib alone prior to induction. Serum was collected pretreatment, after the window, after cycles 1 and 2, at the end of induction, and at each follow-up visit along with restaging computed tomography scans. Next-generation sequencing was used to identify and quantify ctDNA encoding the immunoglobulin receptor sequences in serum as markers of minimal residual disease. Fifty-three patients were enrolled, with a median follow-up of 12.7 years. Patients without detectable ctDNA after 2 cycles of induction had longer progression-free survival (PFS) and overall survival (OS) compared with those with detectable ctDNA (median PFS, 2.7 vs 1.8 years; overall P = .005; median OS, 13.8 vs 7.4 years; overall P = .03). Notably, in vivo assessment of ctDNA dynamics during the bortezomib window was not prognostic, and there was no difference in PFS or OS with bortezomib maintenance. ctDNA monitoring after induction showed that molecular relapse preceded clinical relapse in some cases. In conclusion, interim ctDNA negativity strongly correlates with improved survival and supports the investigation of response-adapted strategies. This trial was registered at www.clinicaltrials.gov as #NCT00114738.

| S-EPMC9043939 | biostudies-literature

Liquid Biopsy in Metastatic Breast Cancer: Current Role of Circulating Tumor Cells and Circulating Tumor DNA.

Project description:BackgroundIn metastatic breast cancer (MBC), blood-based diagnostics have become a major focus of oncological research in the last 2 decades. Detection of circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) has the potential to improve prognosis assessment and complement standard therapy monitoring tools.SummaryTo date, several large analyses have confirmed high CTC counts as an independent prognostic factor. Persistently high CTC numbers during systemic treatment are associated with early progression, but it remains to be clarified which therapeutic options should be offered to such patients since the SWOG 0500 trial failed to show benefit from early switch to another chemotherapy regimen in patients with CTC persistence. In comparison, evidence on the prognostic value of ctDNA is still limited. Most importantly, liquid biopsy-guided treatment interventions have been investigated in several trials. In patients with hormone receptor-positive and HER2-negative MBC, CTC-driven therapy choices resulted in similar PFS to physician's choice treatment. Recently, the DETECT III trial has shown that patients with HER2-negative MBC and HER2-positive CTCs may benefit from targeted anti-HER2 treatment with lapatinib. ctDNA-driven therapy selection has already been approved in clinical routine: alpelisib is the first targeted treatment indicated on the basis of a ctDNA test. Key Messages: CTCs and ctDNA predict clinical outcome and have a potential to improve therapy choices in MBC.

| S-EPMC8985043 | biostudies-literature

Chromosomal instability of circulating tumor DNA reflect therapeutic responses in advanced gastric cancer.

Project description:Gastric cancer is characterized by chromosomal instability. In this study, we investigated chromosomal instability quantified by copy number instability (CNI) score of circulating tumor DNA (ctDNA) during the drug treatment in advanced gastric cancer (AGC). A total of 55 pretherapeutic plasmas from 55 AGC patients and 75 plasmas during drug treatment of 26 AGC patients were collected. Plasma ctDNA was extracted and assessed by whole-genome sequencing (WGS) for somatic copy number alteration (SCNA), and according to which we calculated the CNI scores. We next assessed the correlations between chromosomal instability and therapeutic response. The cutoff value of chromosomal instability was defined as the mean + SD of the CNI scores (56.60) in cfDNA of plasmas from 100 healthy people. For 55 enrolled cases, chromosomal instability was observed in 27 (49%) prior to drug treatment, whose response rate (59%, 16/27) was higher than in 28 patients with stable chromosomes (32%, 9/28, P = 0.043). We also observed that CNI scores fluctuated during treatment in 26 patients. Specifically, the CNI scores in 93% (14/15) of patients sensitive to drug treatment reduced to the level of chromosomal stability and the CNI scores in 52% (13/25) of patients resistant to treatment elevated again. For ctDNA with developed resistance, the SCNA patterns were identical to those before treatment, whereas the CNI scores were lower than the pretherapeutic scores. We found that chromosomal instability based on ctDNA could predict and monitor therapeutic response in gastric cancer, although validation in a larger cohort will be necessary.

| S-EPMC6754425 | biostudies-other

Circulating Tumor DNA Is Capable of Monitoring the Therapeutic Response and Resistance in Advanced Colorectal Cancer Patients Undergoing Combined Target and Chemotherapy.

Project description:Colorectal cancer (CRC) is a highly lethal disease worldwide. The majority of patients receiving targeted therapy or chemotherapy develop drug resistance, while its molecular mechanism remains to be elucidated. The plasma circulating tumor DNA (ctDNA) exhibited the potential in identifying gene variations and monitoring drug resistance in CRC treatment. In this study, we monitored the ctDNA mutational changes in advanced CRC patients underwent first-line therapy with bevacizumab and cetuximab combined with chemotherapy. The mutation spectrum of 43 patients was established by a 605-gene next-generation sequencing (NGS) panel. The baseline measurement shows that genes with the highest mutation frequency were TP53 (74%), APC (58%), KRAS (40%), SYNE1 (33%), LRP1B (23%), TOP1 (23%), and PIK3CA (21%). Mutations in TP53, APC, and KRAS were detected in 29 paired plasma and tissue samples with the consistency of 81, 67, and 42%, respectively. Clinically targetable gene mutations, such as APC, RNF43, SMAD4, BRAD1, KRAS, RAF1, and TP53, were also identified in ctDNA. The overall consistency between ctDNA and tissue samples was 54.6%. Alleviation of mutational burden in BRAF, KRAS, AMER1, and other major driving genes was observed following the first-line therapy. Patients with KRAS and TP53 mutations in tissues appeared to benefit more than the wild-type counterpart. The dynamic change of plasma mutation status was consistent with the tissue tumor burden and was closely correlated with disease progression. In conclusion, ctDNA monitoring is a useful method for molecular genotyping of colorectal cancer patients. Dynamic changes in resistance can be sensitively monitored by gene variation status, which potentially helps to develop treatment strategy.

| S-EPMC7154135 | biostudies-literature

Role of Circulating Tumor DNA in Gastrointestinal Cancers: Current Knowledge and Perspectives

Project description:Simple Summary Management of gastrointestinal (GI) cancers t is a worldwide challenge and some new tools are needed to guide it. Circulating tumor DNA (ctDNA) is a fraction of tumor DNA that can be detected by a liquid biopsy through a simple blood sample. In this work, we tried to summarize in a clinical review to what extend the analysis of ctDNA can improve therapeutic support in digestive oncology and how this circulating biomarker appears as a very promising improvement in addition to classic diagnostic, prognostic and theranostic methods. Although the level of evaluation of this tool is still different between the different GI cancers locations, it is in dynamic evolution in all of them. Abstract Gastrointestinal (GI) cancers are major health burdens worldwide and biomarkers are needed to improve the management of these diseases along their evolution. Circulating tumor DNA (ctDNA) is a promising non-invasive blood and other bodily-fluid-based biomarker in cancer management that can help clinicians in various cases for the detection, diagnosis, prognosis, monitoring and personalization of treatment in digestive oncology. In addition to the well-studied prognostic role of ctDNA, the main real-world applications appear to be the assessment of minimal residual disease to further guide adjuvant therapy and predict relapse, but also the monitoring of clonal evolution to tailor treatments in metastatic setting. Other challenges such as predicting response to treatment including immune checkpoint inhibitors could also be among the potential applications of ctDNA. Although the level of advancement of ctDNA development in the different tumor localizations is still inhomogeneous, it might be now reliable enough to be soon used in clinical routine for colorectal cancers and shows promising results in other GI cancers.

| S-EPMC8507552 | biostudies-literature

Potentiated DNA Damage Response in Circulating Breast Tumor Cells Confers Resistance to Chemotherapy.

Project description:Circulating tumor cells (CTCs) are seeds for cancer metastasis and are predictive of poor prognosis in breast cancer patients. Whether CTCs and primary tumor cells (PTCs) respond to chemotherapy differently is not known. Here, we show that CTCs of breast cancer are more resistant to chemotherapy than PTCs because of potentiated DNA repair. Surprisingly, the chemoresistance of CTCs was recapitulated in PTCs when they were detached from the extracellular matrix. Detachment of PTCs increased the levels of reactive oxygen species and partially activated the DNA damage checkpoint, converting PTCs to a CTC-like state. Inhibition of checkpoint kinases Chk1 and Chk2 in CTCs reduces the basal checkpoint response and sensitizes CTCs to DNA damage in vitro and in mouse xenografts. Our results suggest that DNA damage checkpoint inhibitors may benefit the chemotherapy of breast cancer patients by suppressing the chemoresistance of CTCs and reducing the risk of cancer metastasis.

| S-EPMC4463430 | biostudies-literature

Clinical applications of circulating tumor DNA and circulating tumor cells in pancreatic cancer.

Project description:Pancreatic ductal adenocarcinoma (PDAC) is the most frequent pancreatic cancer type and is characterized by a dismal prognosis due to late diagnosis, local tumor invasion, frequent distant metastases and poor sensitivity to current therapy. In this context, circulating tumor cells and circulating tumor DNA constitute easily accessible blood-borne tumor biomarkers that may prove their clinical interest for screening, early diagnosis and metastatic risk assessment of PDAC. Moreover these markers represent a tool to assess PDAC mutational landscape. In this review, together with key biological findings, we summarize the clinical results obtained using "liquid biopsies" at the different stages of the disease, for early and metastatic diagnosis as well as monitoring during therapy.

| S-EPMC5528974 | biostudies-other

Circulating Tumor DNA Guided Therapeutic Strategies for CRC Patients With Small Pulmonary Nodules

Project description:The clinical diagnosis and treatment of small pulmonary nodules (suspected to be lung metastases) in advanced colorectal cancer patients remain controversy. Previous studies have shown that tumor-informed circulating tumor DNA (ctDNA) blood testing can sensitively detect residual cancer. Postoperative ctDNA in colorectal cancer patients is a valuable biomarker to identify minimal residual disease (MRD) after radical resection, which is possibly useful in redefining the risk group of patients and guiding postoperative treatment. This study aimed to explore the clinical value of therapeutic strategies based on tumor-informed ctDNA test in advanved colorectal cancer patients with small pulmonary nodules.

| 2744776 | ecrin-mdr-crc

The Emerging Role of Circulating Tumor DNA in the Management of Breast Cancer.

Project description:With the incidence of breast cancer steadily rising, it is important to explore novel technologies that can allow for earlier detection of disease as well more a personalized and effective treatment approach. The concept of "liquid biopsies" and the data they provide have been increasingly studied in the recent decades. More specifically, circulating tumor DNA (ctDNA) has emerged as a potential biomarker for various cancers, including breast cancer. While methods such as mammography and tissue biopsies are the current standards for the detection and surveillance of breast cancer, ctDNA analysis has shown some promise. This review discusses the versatility of ctDNA by exploring its multiple emerging uses for the management of breast cancer. Its efficacy is also compared to current biomarkers and technologies.

| S-EPMC8345044 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data