Targeted therapy according to next generation sequencing-based panel sequencing

Saito, Motonobu; Momma, Tomoyuki; Kono, Koji

doi:10.5387/fms.2018-02

Cited by 19 publications

(13 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our study, 23 EGFR mutated patients received second-line liquid biopsy a er the failure of first-generation of Since its introduction in 2007, NGS technology has already made extraordinary advances, making the detection of genetic alterations to guide therapy to be more feasible. And as NGS becomes faster and less expensive, it's sure to be used more frequently and with greater benefit for Chinese NSCLC patients [15]. In our real-world data, 83.33% patients chose NGS-guided targeted therapy in first-line and/or second-line therapy.…”

Section: Discussionmentioning

confidence: 90%

The Value of Next-Generation Sequencing for Treatment in Non-Small Cell Lung Cancer Patients: The Observational, Real-World Evidence in China

Zhang

Shen

Zhou

et al. 2020

BioMed Research International

View full text Add to dashboard Cite

Background. Great success has been made in the targeting therapy of advanced non-small cell lung cancer (NSCLC). Nowadays, next generation sequencing (NGS) is acquirable and affordable in developed area of China. Using this feasible and accurate method of detecting therapeutic genes would help to select optimal treatments to extend patients survival. Here, we identified somatic mutations by NGS and analyzed the value for treatment of NSCLC in a real-world clinical setting. Methods. NGS was carried out on biopsy samples obtained from 66 advanced unresectable NSCLC patients who had not received any treatment. 23 patients received liquid biopsy after failure of first-line targeted treatment. The mutation profiling as well as associations between mutations and clinicopathological characters was analyzed. The study also assessed the values of NGS for choosing treatment options and predicting prognosis in NSCLC patients. Results. 152 somatic mutations were identified in 45 (68.18%) tissue samples. The most frequently mutated genes were EGFR (42.42%), TP53 (31.82%) and KRAS (15.15%). Specifically, the most frequent EGFR mutation subtypes were exon 19 deletion (60.71%) and L858R in exon 21 (46.43%). 83.33% mutated patients received targeted therapy. Among the adenocarcinoma cases, patients with EGFR exon 19 deletion mutation have longer overall survival (OS) than the wide-type (36.0 months versus 19.0 months p=0.046). In addition, in the smoking group, patients with EGFR exon 19 deletion mutation tended to have longer OS (38.0 months versus 16.5 months p<0.01). After the failure of first-line targeted therapy, 23 EGFR mutated patients received liquid biopsy, and the positive rate of T790M mutation in EGFR exon 20 was 47.83%. T790M positive patients have longer progression-free survival (PFS) than the others (15 months versus 9.5 months p=0.025). Conclusions. The observational study from real-world demonstrated that using NGS in routine clinical detection may be useful in guiding the therapy decisions and benefit more Chinese NSCLC patients.

show abstract

Section: Discussionmentioning

confidence: 90%

The Value of Next-Generation Sequencing for Treatment in Non-Small Cell Lung Cancer Patients: The Observational, Real-World Evidence in China

Zhang

Shen

Zhou

et al. 2020

BioMed Research International

View full text Add to dashboard Cite

show abstract

“…Next generation sequencing-based panel sequencing is currently used in daily clinical practice, which could improve the detection of ARID1A mutations in various cancers as well as in GC [31]. In this study, since ARID1Adeficient GC cells are shown to be sensitive to EZH2 inhibitors, a synthetic lethality approach with EZH2 inhibitors should be considered as an additional therapeutic strategy for ARID1A-dificient GC.…”

Section: Discussionmentioning

confidence: 99%

Selective sensitivity of EZH2 inhibitors based on synthetic lethality in ARID1A-deficient gastric cancer

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background AT-rich interactive domain 1A (ARID1A) is a tumor suppressor gene that is frequently mutated in gastric cancer (GC). Although ARID1A mutations are not a druggable target for conventional treatments, novel therapeutic strategies based on a synthetic lethal approach are effective for ARID1A-deficient cancers. The histone methyltransferase EZH2 acts in a synthetic lethal manner in ARID1A-mutated ovarian cancer, although its role in GC remains unknown. Methods The selective sensitivity of the EZH2 inhibitors for ARID1A-deficient GC cells was evaluated using cell viability and colony formation assays. The expression of PI3K/AKT signaling genes were investigated using TCGA's cBioPortal database to determine whether the homeostasis between ARID1A and EZH2 is related to cell proliferation and survival via the PI3K/AKT signaling pathway. We also evaluated the phosphorylation of PI3K/AKT signaling proteins in ARID1A knock downed ARID1A-WT GC cells. Results EZH2 inhibitors decreased the viability of ARID1A-deficient cells in a dose-dependent manner and demonstrated the selective sensitivity to ARID1A-deficient cells in vitro experiment system. Bioinformatics approach revealed that the PI3K/AKT signaling was tended to be activated in ARID1A-deficient GC enhancing cell viability and, furthermore, downregulation of EZH2 in ARID1A-deficient GC was related to normalization of PI3K/AKT signaling pathway. The cell experiment revealed that phosphorylated AKT was upregulated in ARID1A-deficent GC cells. Conclusions The present findings provide a rationale for the selective sensitivity of EZH2 inhibitors against ARID1Adeficient GC and suggest the potential efficacy of targeted therapy using EZH2 inhibitors in this patient population.

show abstract

“…The identification of new molecular targets and the availability of modern immunotherapeutic approaches have revolutionized the treatment of advanced melanoma. By enabling the detection of genomic, transcriptional and epigenetic changes, NGS has allowed the identification of specific targets, thereby allowing for the development and optimization of treatments interfering with specific molecular targets [ 10 , 11 ]. Although such novel therapeutic approaches have demonstrated clinical efficacy and rapid responses in most patients, acquired resistance represents a significant challenge and has yet to be overcome.…”

Section: Melanoma Targeted Therapy and Immunotherapy: An Overviewmentioning

confidence: 99%

Tumor Microenvironment: Implications in Melanoma Resistance to Targeted Therapy and Immunotherapy

Falcone

Cognetti

Bazzichetto

et al. 2020

Cancers

View full text Add to dashboard Cite

Antitumor therapies have made great strides in recent decades. Chemotherapy, aggressive and unable to discriminate cancer from healthy cells, has given way to personalized treatments that, recognizing and blocking specific molecular targets, have paved the way for targeted and effective therapies. Melanoma was one of the first tumor types to benefit from this new care frontier by introducing specific inhibitors for v-Raf murine sarcoma viral oncogene homolog B (BRAF), mitogen-activated protein kinase kinase (MEK), v-kit Hardy–Zuckerman 4 feline sarcoma viral oncogene homolog (KIT), and, recently, immunotherapy. However, despite the progress made in the melanoma treatment, primary and/or acquired drug resistance remains an unresolved problem. The molecular dynamics that promote this phenomenon are very complex but several studies have shown that the tumor microenvironment (TME) plays, certainly, a key role. In this review, we will describe the new melanoma treatment approaches and we will analyze the mechanisms by which TME promotes resistance to targeted therapy and immunotherapy.

show abstract

Targeted therapy according to next generation sequencing-based panel sequencing

Cited by 19 publications

References 29 publications

The Value of Next-Generation Sequencing for Treatment in Non-Small Cell Lung Cancer Patients: The Observational, Real-World Evidence in China

The Value of Next-Generation Sequencing for Treatment in Non-Small Cell Lung Cancer Patients: The Observational, Real-World Evidence in China

Selective sensitivity of EZH2 inhibitors based on synthetic lethality in ARID1A-deficient gastric cancer

Tumor Microenvironment: Implications in Melanoma Resistance to Targeted Therapy and Immunotherapy

Contact Info

Product

Resources

About