Genomic medicine and cancer clinical trial in Thailand.
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ABSTRACT:
SUBMITTER: Thamlikitkul L
PROVIDER: S-EPMC10875286 | biostudies-literature | 2023 Aug
REPOSITORIES: biostudies-literature
Publications
Genomic medicine and cancer clinical trial in Thailand.
Thamlikitkul Lucksamon L Parinyanitikul Napa N Sriuranpong Virote V
Cancer biology & medicine 20230801 1
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Project description:Transcriptomic profiling of metastatic NSCLC cancer patients from tumor tissue and organ-matched normal tissue as reference which were taken as part of the WINTHER clinical trial. The organ-matched normal tissues were used in order to eliminate host gene expression variability while discarding most genetic variability between individuals. The goal was to trial was to navigate patients to therapy on the basis of fresh biopsy-derived DNA sequencing or RNA expression
2021-04-09 | GSE171702 | GEO
Project description:Precision medicine focuses on DNA abnormalities, but not all tumors have tractable genomic alterations. The WINTHER trial ( NCT01856296 ) navigated patients to therapy on the basis of fresh biopsy-derived DNA sequencing (arm A; 236 gene panel) or RNA expression (arm B; comparing tumor to normal). The clinical management committee (investigators from five countries) recommended therapies, prioritizing genomic matches; physicians determined the therapy given. Matching scores were calculated post-hoc for each patient, according to drugs received: for DNA, the number of alterations matched divided by the total alteration number; for RNA, expression-matched drug ranks. Overall, 303 patients consented; 107 (35%; 69 in arm A and 38 in arm B) were evaluable for therapy. The median number of previous therapies was three. The most common diagnoses were colon, head and neck, and lung cancers. Among the 107 patients, the rate of stable disease ≥6 months and partial or complete response was 26.2% (arm A: 23.2%; arm B: 31.6% (P = 0.37)). The patient proportion with WINTHER versus previous therapy progression-free survival ratio of >1.5 was 22.4%, which did not meet the pre-specified primary end point. Fewer previous therapies, better performance status and higher matching score correlated with longer progression-free survival (all P < 0.05, multivariate). Our study shows that genomic and transcriptomic profiling are both useful for improving therapy recommendations and patient outcome, and expands personalized cancer treatment.
| S-EPMC6599610 | biostudies-literature
Project description:BACKGROUND:Increasing affordability of next-generation sequencing (NGS) has created an opportunity for realizing genomically-informed personalized cancer therapy as a path to precision oncology. However, the complex nature of genomic information presents a huge challenge for clinicians in interpreting the patient's genomic alterations and selecting the optimum approved or investigational therapy. An elaborate and practical information system is urgently needed to support clinical decision as well as to test clinical hypotheses quickly. RESULTS:Here, we present an integrated clinical and genomic information system (CGIS) based on NGS data analyses. Major components include modules for handling clinical data, NGS data processing, variant annotation and prioritization, drug-target-pathway analysis, and population cohort explorer. We built a comprehensive knowledgebase of genes, variants, drugs by collecting annotated information from public and in-house resources. Structured reports for molecular pathology are generated using standardized terminology in order to help clinicians interpret genomic variants and utilize them for targeted cancer therapy. We also implemented many features useful for testing hypotheses to develop prognostic markers from mutation and gene expression data. CONCLUSIONS:Our CGIS software is an attempt to provide useful information for both clinicians and scientists who want to explore genomic information for precision oncology.
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Project description: Not available
| S-EPMC6160705 | biostudies-literature
Project description:AimDevelop and apply a comprehensive and accurate next-generation sequencing based assay to help clinicians to match oncology patients to therapies.Materials & methodsThe performance of the CANCERPLEX® assay was assessed using DNA from well-characterized routine clinical formalin-fixed paraffin-embedded (FFPE) specimens and cell lines.ResultsThe maximum sensitivity of the assay is 99.5% and its accuracy is virtually 100% for detecting somatic alterations with an allele fraction of as low as 10%. Clinically actionable variants were identified in 93% of patients (930 of 1000) who underwent testing.ConclusionThe test's capacity to determine all of the critical genetic changes, tumor mutation burden, microsatellite instability status and viral associations has important ramifications on clinical decision support strategies, including identification of patients who are likely to benefit from immune checkpoint blockage therapies.
| S-EPMC5580078 | biostudies-literature
Project description:In pediatric cancer precision medicine clinical trials settings, parents proactively seeking treatment and answers to causation may request return of their child's raw data and/or biospecimen. To satisfy such requests, the ZERO Childhood Cancer Program required a guidance document. Literature review led to Version(V)1; Delphi consultation with 21/54 invited experts (V2-4) and parent consultations (V5-6). A final V7 was approved for implementation: Policy (purpose; background; ethical considerations), Process (nine steps), and consent form. Issues addressed included: child's best interests, clinical utility, non-maleficence, reciprocity between researchers and participants/parents; responsibility to genetic relatives; acknowledging potential value of subsequent analysis/interpretation but no obligation on treating clinicians to act on therapeutic recommendations arising; practical barriers to return; and supporting parental empowerment by facilitating meeting with a study genetic counselor, separate from their treating clinician, if preferred, to manage their request. This guide may be a model for other research groups and inform ethical guidelines.
| S-EPMC11832931 | biostudies-literature
Project description:Introduction In HR+/HER2- metastatic breast cancer (MBC) is imperative to identify patients who respond poorly to CDK4/6i and to discover therapeutic targets to reverse this resistance. Non-luminal breast cancer subtype and high levels of CCNE1 are candidate biomarkers in this setting but further validation is needed. Methods We performed mRNA gene expression profiling and correlation with progression-free-survival (PFS) on 455 tumor samples included in the phase III PEARL study, that assigned HR+/HER2- MBC patients to receive palbociclib+ET vs capecitabine. ER+/HER2- breast cancer cell lines were used to generate and characterize resistance to palbociclib+ET. Results Non-luminal subtype was more prevalent in metastatic (14%) than in primary tumor samples (4%). Patients with non-luminal tumors had median PFS of 2.4months (m) with palbociclib+ET and 9.3m with capecitabine; HR:4.16, adjusted p-value<0.0001. Tumors with high CCNE1 expression (above median) had also worse median PFS with palbociclib+ET (6.2m) than with capecitabine (9.3m); HR:1.55, adjusted p-value=0.0036. In patients refractory to palbociclib+ET (PFS in the lower quartile) we found higher levels of Polo Like Kinase 1 (PLK1). In an independent data set (PALOMA3), tumors with high PLK1 show worse median PFS than those with low PLK1 expression under palbociclib+ET treatment. In ER+/HER2- cell line models we show that PLK1 inhibition reverses resistance to palbociclib+ET. Conclusion We confirm the association of non-luminal subtype and CCNE1 with resistance to CDK4/6i+ET in HR+ MBC. High levels of PLK1 mRNA identify patients with poor response to palbociclib, suggesting PLK1 could also play a role in the setting of resistance to CDK4/6i.
2023-01-26 | GSE223700 | GEO
Project description:Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial
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Project description:EORTC 10994 is a phase III clinical trial comparing FEC with ET in patients with large operable, locally advanced or inflammatory breast cancer (www.eortc.be). Frozen biopsies were taken at randomisation. RNA was extracted from 100um thickness of 14G core needle biopsies. Adjacent sections were tested by H&E to confirm >20% tumour cell content. 100 ng total RNA per chip were amplified using the Affymetrix small sample protocol (IVT then Enzo). 49 tumours were tested on Affymetrix U133A chips. The CEL files were quantile normalised together using rma. Clinical response data are not available yet. Keywords = Apocrine carcinoma Keywords = breast cancer
2005-06-01 | GSE1561 | GEO
Project description:Genomic and transcriptomic profiling expands precision cancer medicine: the WINTHER trial (Lung patients)
| PRJNA720621 | ENA