HER2-Directed Therapy in Advanced Gastric and Gastroesophageal Adenocarcinoma: Triumphs and Troubles

Grieb, Brian C.; Agarwal, Rajiv

doi:10.1007/s11864-021-00884-7

Cited by 18 publications

(14 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Olaparib has been approved by the FDA and the EMA for addressing homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer in 2020 [35], after the date of testing reported for these samples. Additionally, a gastric adenocarcinoma presenting ERBB2 amplification may currently potentially benefit from the recently FDA-approved trastuzumab deruxtecan for adult patients with locally advanced or metastatic HER2-positive gastric adenocarcinoma [36]. Other biomarkers detected in this study were the presence of BRAF V600K alteration and wild-type NRAS derived from melanoma and colon adenocarcinoma samples.…”

Section: Discussionmentioning

confidence: 76%

A Real-World Study Reporting the Use of Foundation Medicine® Testing in Portugal

Pinto

Schmitt

2023

JMP

View full text Add to dashboard Cite

Foundation Medicine® testing is a next-generation sequence (NGS)-based platform that allows clinicians to obtain the comprehensive genomic profiling (CGP) of several cancers. By using NGS approaches, relevant genomic alterations can be identified in a short timeframe, providing guidance to diagnostic and therapeutic decisions. This study reports the implementation of three commercially available Foundation Medicine® tests in a Portuguese institution and explores the genomic alterations identified. Data obtained from 72 patients tested with Foundation Medicine® between July 2017 and December 2020 were analysed retrospectively. A total of 290 gene alterations were identified, and TP53 was the gene most frequently altered. Among the 67 successfully profiled samples, 37.3% presented a potentially actionable variation. Breast carcinoma represented the most frequent tumour-carrying variation that can be targeted using currently approved drugs. A limited number of potentially actionable variants using approved drugs was found in this study; however, the genomic information provided by Foundation Medicine® may help clinicians in directing cancer patients into clinical trials or to off-label treatments.

show abstract

Section: Discussionmentioning

confidence: 76%

A Real-World Study Reporting the Use of Foundation Medicine® Testing in Portugal

Pinto

Schmitt

2023

JMP

View full text Add to dashboard Cite

show abstract

“…Currently, the most studied therapy is related to HER2 expression. While early studies disagreed on the prognostic relevance of HER status, recent evidence highlights its value [ 54 , 55 ]. In 2010, the Toga Study evaluated the use of the HER2-targeted monoclonal antibody trastuzumab with standard chemotherapy in 584 patients.…”

Section: Discussionmentioning

confidence: 99%

Survival Outcomes of Hepatectomy in Gastric Cancer Liver Metastasis: A Systematic Review and Meta-Analysis

Conde

Ibáñez-Pinilla

Sabogal

et al. 2023

JCM

View full text Add to dashboard Cite

Gastric cancer liver metastasis (GCLM) is a contraindication for surgical treatment in current guidelines. However, the results of recent studies are questioning this paradigm. We assessed survival outcomes and their predictors following hepatectomy for GCLM in a systematic review of studies published from 2000 to 2022 according to PRISMA guidelines. We identified 42,160 references in four databases. Of these, 55 articles providing data from 1990 patients fulfilled our criteria and were included. We performed a meta-analysis using random-effects models to assess overall survival (OS) and disease-free survival (DFS) at one, three, and five years post-surgery. We studied the impact of potential prognostic factors on survival outcomes via meta-regression. One, three, and five years after surgery, OS was 69.79%, 34.79%, and 24.68%, whereas DFS was 41.39%, 23.23%, and 20.18%, respectively. Metachronous presentation, well-to-moderate differentiation, small hepatic tumoral size, early nodal stage, R0 resection, unilobar compromisation, and solitary lesions were associated with higher overall survival. Metachronous presentation, smaller primary tumoral size, and solitary metastasis were linked to longer DFS. The results of our meta-analysis suggest that hepatectomy leads to favorable survival outcomes in patients with GCLM and provides data that might help select patients who will benefit most from surgical treatment.

show abstract

“…Interestingly, the DrugBank analysis showed that the drug targeting GAA was Trastuzumab-deruxtecan. Trastuzumab-deruxtecan is primarily used for patients with human epidermal growth factor receptor 2 (HER2)-mutant tumours including non-SCLC and in the absence of SCLC (79)(80)(81). Upon binding to HER2, Trastuzumab-deruxtecan disrupts the HER2 signalling, undergoes internalisation and intracellular linker cleavage by lysosomal enzymes and ultimately causes DNA damage and apoptotic cell death (80).…”

Section: Discussionmentioning

confidence: 99%

Multi-Omics Integration-Based Prioritisation of Competing Endogenous RNA Regulation Networks in Small Cell Lung Cancer: Molecular Characteristics and Drug Candidates

Wang

Gao

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

BackgroundThe competing endogenous RNA (ceRNA) network-mediated regulatory mechanisms in small cell lung cancer (SCLC) remain largely unknown. This study aimed to integrate multi-omics profiles, including the transcriptome, regulome, genome and pharmacogenome profiles, to elucidate prioritised ceRNA characteristics, pathways and drug candidates in SCLC.MethodWe determined the plasma messenger RNA (mRNA), microRNA (miRNA), long noncoding RNA (lncRNA) and circular RNA (circRNA) expression levels using whole-transcriptome sequencing technology in our SCLC plasma cohort. Significantly expressed plasma mRNAs were then overlapped with the Gene Expression Omnibus (GEO) tissue mRNA data (GSE 40275, SCLC tissue cohort). Next, we applied a multistep multi-omics (transcriptome, regulome, genome and pharmacogenome) integration analysis to first construct the network and then to identify the lncRNA/circRNA-miRNA-mRNA ceRNA characteristics, genomic alterations, pathways and drug candidates in SCLC.ResultsThe multi-omics integration-based prioritisation of SCLC ceRNA regulatory networks consisted of downregulated mRNAs (CSF3R/GAA), lncRNAs (AC005005.4-201/DLX6-AS1-201/NEAT1-203) and circRNAs (hsa_HLA-B_1/hsa_VEGFC_8) as well as upregulated miRNAs (hsa-miR-4525/hsa-miR-6747-3p). lncRNAs (lncRNA-AC005005.4-201 and NEAT1-203) and circRNAs (circRNA-hsa_HLA-B_1 and hsa_VEGFC_8) may regulate the inhibited effects of hsa-miR-6747-3p for CSF3R expression in SCLC, while lncRNA-DLX6-AS1-201 or circRNA-hsa_HLA-B_1 may neutralise the negative regulation of hsa-miR-4525 for GAA in SCLC. CSF3R and GAA were present in the genomic alteration, and further identified as targets of FavId and Trastuzumab deruxtecan, respectively. In the SCLC-associated pathway analysis, CSF3R was involved in the autophagy pathways, while GAA was involved in the glucose metabolism pathways.ConclusionsWe identified potential lncRNA/cirRNA-miRNA-mRNA ceRNA regulatory mechanisms, pathways and promising drug candidates in SCLC, providing novel potential diagnostics and therapeutic targets in SCLC.

show abstract

HER2-Directed Therapy in Advanced Gastric and Gastroesophageal Adenocarcinoma: Triumphs and Troubles

Cited by 18 publications

References 82 publications

A Real-World Study Reporting the Use of Foundation Medicine® Testing in Portugal

A Real-World Study Reporting the Use of Foundation Medicine® Testing in Portugal

Survival Outcomes of Hepatectomy in Gastric Cancer Liver Metastasis: A Systematic Review and Meta-Analysis

Multi-Omics Integration-Based Prioritisation of Competing Endogenous RNA Regulation Networks in Small Cell Lung Cancer: Molecular Characteristics and Drug Candidates

Contact Info

Product

Resources

About