Structure-Based QSAR Modeling of RET Kinase Inhibitors from 49 Different 5,6-Fused Bicyclic Heteroaromatic Cores to Patent-Driven Validation DOI Creative Commons

Sumin Jin,

Surendra Kumar, Mi‐Hyun Kim

et al.

ACS Omega, Journal Year: 2024, Volume and Issue: 9(50), P. 49662 - 49673

Published: Dec. 6, 2024

RET receptor tyrosine kinase is crucial for nerve and tissue development but can be an important oncogenic driver. This study focuses on exploring the design principles of potent inhibitors through molecular docking 3D-QSAR modeling 5,6-fused bicyclic heteroaromatic derivatives. First all, 49 different substructures were collected from five data sources selected simulations. QSAR models built 3399 conformers 952 using partial least-squares method statistically evaluated. The optimal model exhibited high predictive performance, with

Language: Английский

Improvement of assessment in surrogate endpoint and safety outcome of single-arm trials for anticancer drugs DOI
Yafang Huang, Jinqiu Yuan

Expert Review of Clinical Pharmacology, Journal Year: 2024, Volume and Issue: 17(5-6), P. 477 - 487

Published: April 18, 2024

Single-arm trials (SATs) and surrogate endpoints were adopted as pivotal evidence for accelerated approval of anticancer drugs more than 30 years. However, concerns regarding clinical quality in trials, particularly the SATs have increasingly been raised. SAT may not always provide strong due to lack control endpoint overall survival that is typically present randomized controlled trials. Clinical trial adjudication a crucial factor outcome measurement ensure data drugs. In this review, we systematically discuss characteristics adjudications assessments safety respectively, which are essential ensuring reliable transparent outcomes. Endpoint effectively reduces potential bias mitigates variance be introduced by investigators when analyzing medical records endpoints. We analyze advantages disadvantages each type adjudicator summary roles adjudicators. By suggestion improving reliability transparency review aims supply strategy better investigation drugs, ultimately leading patient

Language: Английский

Citations

3
Rapid and Cost-Efficient Detection of RET Rearrangements in a Large Consecutive Series of Lung Carcinomas DOI Open Access
Vladislav I. Tiurin, Elena V. Preobrazhenskaya, Natalia V. Mitiushkina

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(13), P. 10530 - 10530

Published: June 23, 2023

RET-kinase-activating gene rearrangements occur in approximately 1–2% of non-small-cell lung carcinomas (NSCLCs). Their reliable detection requires next-generation sequencing (NGS), while conventional methods, such as immunohistochemistry (IHC), fluorescence situ hybridization (FISH) or variant-specific PCR, have significant limitations. We developed an assay that compares the level RNA transcripts corresponding to 5′- and 3′-end portions RET gene; this test relies on fact translocations result upregulation kinase domain and, therefore, 5′/3′-end expression imbalance. The present study included 16,106 consecutive NSCLC patients, 14,449 (89.7%) whom passed cDNA quality control. unbalanced was observed 184 (1.3%) tumors, 169 which had a sufficient amount material for identification translocation variants. Variant-specific PCR revealed 155/169 (91.7%) tumors. RNA-based NGS 10 cases, 8 carried exceptionally rare novel (HOOK1::RET ZC3H7A::RET) translocations. also applied eight common 4680 emerged negative upon test; 33 (0.7%) these NSCLCs showed fusion. While combination analysis imbalance allowed 2% NSCLCs, estimate approached 120/2361 (5.1%) EGFR/KRAS/ALK/ROS1/BRAF/MET-negative carcinomas. RET-rearranged tumors obtained from females, but not males, decreased thymidylate synthase (p < 0.00001), is known predictive marker efficacy pemetrexed. results our provide viable alternative testing facilities do access due cost technical

Language: Английский

Citations

7
Molecular genetics, therapeutics and RET inhibitor resistance for medullary thyroid carcinoma and future perspectives DOI Creative Commons
Ying Zhang, Weihui Zheng,

Shihong Zhou

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Sept. 28, 2024

Language: Английский

Citations

2
First-line versus second-line use of pralsetinib in treatment of rearranged during transfection (RET) fusion-positive advanced non-small cell lung cancer: a cost-effectiveness analysis DOI Open Access
Wenjie Liu, Gengwei Huo, Mengjie Li

et al.

Translational Lung Cancer Research, Journal Year: 2023, Volume and Issue: 12(9), P. 1949 - 1958

Published: Sept. 1, 2023

The ARROW study demonstrated favorable clinical efficacy and safety of pralsetinib (PRL) in treating rearranged during transfection (RET) fusion positive non-small cell lung cancer (NSCLC) trials. However, due to the high cost PRL, evaluating its cost-effective characteristics is crucial. Currently, there has been no cost-effectiveness analysis specifically for PRL. Therefore, aim this was assess using PRL as a first-line therapy versus reserving it until second-line solely relying on chemotherapy from perspective payers United States.A Markov model developed evaluate 3 above mentioned PRL-based treatment strategies. Clinical data trial were incorporated into model, costs utilities values obtained through previously published literature public databases, with both being discounted at 3% per year. To ensure robustness probabilistic univariate sensitivity analyses performed. primary endpoints included quality-adjusted life years (QALYs), lifetime costs, incremental ratio (ICER).Compared chemotherapy, use resulted an additional 0.07 QALYs $133,561, ICER $1,353,849.65 QALY. Similarly, when used setting, led 0.09 $92,797, $559,232.70 value or strategy higher than US willingness-to-pay (WTP) threshold $150,000 Univariable revealed that utility progressed disease had most significant impact ICER. be considered WTP QALY, would need reduced by 71.34% 84.49% treatment.Based current pricing, neither nor found patients RET fusion-positive advanced NSCLC compared chemotherapy. Reserving may compromise approach maintaining control over healthcare expenses yet still achieving outcomes.

Language: Английский

Citations

5
RET Fusion Testing in Patients With NSCLC: The RETING Study DOI Creative Commons
Esther Conde, Susana Hernández,

Jose Luis Rodriguez Carrillo

et al.

JTO Clinical and Research Reports, Journal Year: 2024, Volume and Issue: 5(4), P. 100653 - 100653

Published: Feb. 20, 2024

inhibitors with impressive overall response rates are now available for patients NSCLC, yet the identification of

Language: Английский

Citations

1
Selpercatinib: A narrative drug review DOI Creative Commons

Priyadarshini Eashwar Raj,

Rekabtala Bhaskar,

Anne Srikanth

et al.

Cancer Research Statistics and Treatment, Journal Year: 2024, Volume and Issue: 7(1), P. 82 - 90

Published: Jan. 1, 2024

Rearranged during transfection ( RET ) alteration promotes oncogenesis in a few cancers. mutation positivity is seen approximately 70% of medullary thyroid cancers, around 30% differentiated papillary and 1-2% non-small-cell lung cancers (NSCLC). To write this narrative drug review, we searched various websites like the United States Food Drug Administration, PubMed, Google Scholar, UpToDate, recently published papers international conferences using search terms “RET,” “RET alteration,” “Retevmo,” inhibitors,” “selpercatinib.” We shortlisted 31 articles between January 1980 2024. discuss history, mechanism action, resistance, pharmacodynamics, pharmacokinetics, dosing, toxicity, pivotal trials, indications selpercatinib. Selective inhibitors selpercatinib are indicated treatment -altered NSCLC cancer.

Language: Английский

Citations

1
Efficacy of immunotherapy in RET fusion-positive NSCLC: A meta-analysis DOI Creative Commons
Zhongsheng Peng, Kaibo Ding,

Mingying Xie

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(14), P. e34626 - e34626

Published: July 1, 2024

The Rearranged during Transfection (

Language: Английский

Citations

1
Case report: Eczematous adverse drug reaction after selpercatinib treatment DOI Creative Commons

Bingrun Li,

Peng Cao,

Wenjing Xu

et al.

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: Dec. 24, 2024

This study reports a 50-year-old patient presented with eczematous drug-eruption induced by selpercatinib after the treatment of non-small cell lung cancer (NSCLC). The has symmetric erythematous papules and plaques all over body dry, scaly skin accompanied severe pruritus visible scarring. After systemic glucocorticoids, patient’ lesions were reduced well. Currently, medical literature on incidence selpercatinib-induced cutaneous reactions their clinical management is scarce. Therefore, this provides novel evidence for reactions.

Language: Английский

Citations

1
Sustained Clinical Response to 4th-Line Therapy with Selpercatinib in RET Fusion-Positive Combined Small Cell Lung Cancer DOI Creative Commons
Yan Huang, Shuang Dai,

Wenlian Yin

et al.

OncoTargets and Therapy, Journal Year: 2023, Volume and Issue: Volume 16, P. 1015 - 1020

Published: Nov. 1, 2023

Objective: Combined small cell lung cancer (C-SCLC) is a relatively rare subtype of (SCLC) which combines SCLC and any component non-small carcinoma (NSCLC). Patients diagnosed with C-SCLC are currently recommended to receive the same treatment as cases in absence clear evidence suggesting different strategies. The genomic profiling rarely studied. Herein, we report case extensive-stage harboring KIF5B-RET fusion before first-line therapy persistent sensitivity fourth-line selpercatinib reported. Materials Methods: Molecular pathological features were evaluated using transbronchial biopsy, immunohistochemical (IHC) staining next-generation sequencing (NGS). Results: NGS revealed tumor. patient had progression-free survival (PFS) surpassing 14 months after treatment, ongoing clinical response 4th-line treatment. Conclusion: This highlights importance comprehensive molecular testing for selecting optimal Although RET patients C-SCLC, its identification selective inhibitors may contribute benefits. Keywords: combined cancer, rearranged during transfection, selpercatinib,

Language: Английский

Citations

3
Lung Cancer DOI
Guy Berchem, Solange Peters

Springer eBooks, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 29

Published: Jan. 1, 2024

Language: Английский

Citations

0