Exploring acenocoumarol and silodosin as allosteric EGFR inhibitors for the treatment of non-small cell lung cancer DOI Creative Commons
Swastika Maity, Krishnaprasad Baby,

Bharath Harohalli Byregowda

et al.

F1000Research, Journal Year: 2024, Volume and Issue: 13, P. 1398 - 1398

Published: Nov. 21, 2024

Background Non-small-cell lung cancer (NSCLC) is a highly morbid disease. Chemotherapy for NSCLC lacks specificity and efficacy mainly because of drug resistance. The current study aimed to explore computational tools target allosteric epidermal growth factor receptor (EGFR) sites screen the top molecules in vitro vivo xenograft models. Methods Molecular docking, virtual screening, molecular dynamic studies revealed that acenocoumarol silodosin are two EGFR inhibitors. They were further tested cytotoxicity, apoptosis, cell cycle, gene expression by qPCR, western blotting, A549 anti-proliferative activity, tumor regression analysis. Results Acenocoumarol exhibited cytotoxicity in IMR-90 cells at concentrations below 50 80 μM, respectively. induced S-phase G2/M-phase arrest cycle Both drugs showed early apoptosis their IC50 doses (acenocoumarol μM 25 μM). KRAS (Kirsten rat sarcoma viral oncogene homolog) ERK2 (extracellular signal-regulated kinase 2) regulation was confirmed using qPCR. activities quantified blot In study, size, body weight, organ weight significantly attenuated test compared with standard cisplatin. Immunoblotting results A549-xenograft tissue indicated downregulation ERK2. Furthermore, have upregulated caspase-3 expression. Conclusion downregulate both line Xenograft model. associated inhibition. Hence, can be explored repurposing human trials.

Language: Английский

Unveiling the Landscape of Uncommon EGFR Mutations in NSCLC-A Systematic Review DOI Creative Commons
Maxime Borgeaud, Kaushal Parikh, Giuseppe Luigi Banna

et al.

Journal of Thoracic Oncology, Journal Year: 2024, Volume and Issue: 19(7), P. 973 - 983

Published: March 16, 2024

Language: Английский

Citations

25
Recent Advances in Structural Optimization of Quinazoline-Based Protein Kinase Inhibitors for Cancer Therapy (2021–Present) DOI Creative Commons
Heba T. Abdel‐Mohsen, Manal M. Anwar, Nesreen S. Ahmed

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(4), P. 875 - 875

Published: Feb. 16, 2024

Cancer is a complicated, multifaceted disease that can impact any organ in the body. Various chemotherapeutic agents have low selectivity and are very toxic when used alone or combination with others. Resistance one of most important hurdles develop due to use many anticancer therapeutics. As result, treating cancer requires target-specific palliative care strategy. Remarkable scientific discoveries shed light on several molecular mechanisms underlying cancer, resulting development various targeted agents. One heterocyclic motifs quinazoline, which has wide range biological uses chemical reactivities. Newer, more sophisticated medications quinazoline structures been found last few years, great strides made creating effective protocols for building these pharmacologically active scaffolds. A new class known as quinazoline-based derivatives possessing properties consists well-known compounds block different protein kinases other targets. This review highlights recent updates (2021–2024) acting against chemotherapeutics. It also provides guidance design synthesis novel analogues could serve lead compounds.

Language: Английский

Citations

12
Afatinib for the Treatment of NSCLC with Uncommon EGFR Mutations: A Narrative Review DOI Creative Commons
Yingying Jiang,

Xiaoxu Fang,

Yan Xiang

et al.

Current Oncology, Journal Year: 2023, Volume and Issue: 30(6), P. 5337 - 5349

Published: May 28, 2023

Afatinib, the world’s first irreversible ErbB family (containing four different cancer cell epidermal growth factor receptors, including EGFR, HER2, ErbB3, and ErbB4) inhibitor, is a second-generation oral receptor tyrosine kinase inhibitor (EGFR-TKI). It can be used as first-line treatment for locally advanced or metastatic non-small-cell lung (NSCLC) with an EGFR-sensitive mutation patients squamous whose disease progresses during after platinum-containing chemotherapy. Currently, use of third-generation EGFR-TKIs, afatinib no longer clinically indicated choice NSCLC who have mutations. However, showed considerable inhibitory effect in uncommon EGFR mutations (G719X, S768I, L861Q) according to combined post hoc analysis LUX-Lung2/3/6 trials. With development genetic testing technology, detection rate increasing. The aim this paper describe detail sensitivity rare provide information reference those suffering from

Language: Английский

Citations

17
The difference between dacomitinib and afatinib in effectiveness and safety in first-line treatment of patients with advanced EGFR-mutant non-small cell lung cancer: a real-world observational study DOI Creative Commons
Wen‐Chien Cheng, Chi‐Chen Lin, Wei‐Chih Liao

et al.

BMC Cancer, Journal Year: 2024, Volume and Issue: 24(1)

Published: Feb. 19, 2024

The irreversible epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) afatinib and dacomitinib are approved for first-line treatment of EGFR mutation-positive non-small cell lung cancer (NSCLC). We aimed to compare the efficacy safety in this setting.

Language: Английский

Citations

2
Optimal first-line treatment for EGFR-mutated NSCLC: a comparative analysis of osimertinib and second-generation EGFR-TKIs DOI Creative Commons

Hsu-Yuan Chen,

Chia‐Hung Chen, Wei‐Chih Liao

et al.

BMC Pulmonary Medicine, Journal Year: 2024, Volume and Issue: 24(1)

Published: Oct. 16, 2024

Osimertinib is an irreversible third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). It the preferred first-line treatment for EGFR-mutated non-small cell lung cancer (NSCLC) compared to first-generation EGFR-TKIs. However, limited research has its clinical effectiveness with second-generation (2

Language: Английский

Citations

2
Catalytic Lysine745 Targeting Strategy in Fourth-Generation EGFR Tyrosine Kinase Inhibitors to Address C797S Mutation Resistance DOI

Bhatu Patil,

Harun Patel

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 283, P. 117140 - 117140

Published: Dec. 10, 2024

Language: Английский

Citations

2
Strategies for enhancing non-small cell lung cancer treatment: Integrating Chinese herbal medicines with epidermal growth factor receptor-tyrosine kinase inhibitors therapy DOI
Lin Chen,

Wen-Da Chen,

Yuxin Xu

et al.

European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 980, P. 176871 - 176871

Published: Aug. 6, 2024

Language: Английский

Citations

1
Protein Kinase Inhibitors Indicated for Lung Cancer: Pharmacodynamics, Pharmacokinetics, Adverse Drug Reactions, and Evaluation in Clinical Trials DOI Creative Commons
Constance Bordet,

Vincent Dongay,

Yoann Zelmat

et al.

Journal of Clinical Pharmacy and Therapeutics, Journal Year: 2024, Volume and Issue: 2024(1)

Published: Jan. 1, 2024

What Is Known and Objective . Anti‐EGFR (epidermal growth factor receptor) drugs are indicated for non‐small‐cell lung cancer (NSCLC). This review summarises the information available to date on first anti‐EGFRs granted market authorisation: erlotinib TARCEVA®, gefitinib IRESSA®, afatinib GIOTRIF®, dacomitinib VIZIMPRO®, osimertinib TAGRISSO®. Methods A literature search was conducted in PubMed database including studies published English using terms gefitinib, erlotinib, afatinib, dacomitinib, osimertinib. Furthermore, bibliographies of selected references were also studied relevant articles. Clinical trial (CT) data extracted from clinicaltrials.gov (ongoing trials adverse events (AEs)). Assessment AEs these global pharmacovigilance VigiBase®. Results Discussion Erlotinib first‐generation anti‐EGFR drugs, able bind competitively reversibly ATP‐ (adenosine triphosphate‐) binding site EGFR exon 19 21 mutations. Afatinib second‐generation covalently irreversibly ATP inhibit HER (human epidermal such as HER2 HER4 enzyme activity. Osimertinib is a third‐generation PKI overcomes T790M gatekeeper mutation through covalent at site. Medical interactions with reported, notably cytochrome P450 inducers or inhibitors. The most reported CTs cutaneous reactions gastrointestinal disorders. occurrence less third generation than first‐ drugs. These results consistent VigiBase® database. New Conclusion current knowledge regarding five literature. appears be more effective second generations first‐line therapy. registered NCT01523587 , NCT01466660 NCT01774721 NCT01360554 NCT02296125

Language: Английский

Citations

1
The treatment of patients with non-small cell lung cancer carrying uncommon EGFR mutations, HER2 mutations, or brain metastases: a systematic review of pre-clinical and clinical findings for dacomitinib DOI Open Access
Li-Li Yang,

X. Luo,

Lingling Xie

et al.

Translational Cancer Research, Journal Year: 2023, Volume and Issue: 12(8), P. 2197 - 2211

Published: Aug. 1, 2023

Accumulating evidence has shown that dacomitinib potential activities for patients with non-small cell lung cancer (NSCLC) harboring uncommon epidermal growth factor receptor (EGFR) mutations, human 2 (HER2) or central nervous system (CNS) metastases.This study aimed to give a systematic review on its applications in the above settings by searching MEDLINE/PubMed, Embase, Cochrane Library, American Society of Clinical Oncology.org, European Medical and ClinicalTrials.gov.The literature search yielded 649 publications total. According our findings, exhibited promising efficacy major EGFR mutations (including G719X, S768I, L861Q). Both exon 20 insertional mutation (Ex20ins) HER2 Ex20ins demonstrated significant internal heterogeneity response dacomitinib, among which specific subtypes D770delinsGY, A763_Y764insFQEA, M774delinsWLV) were highly sensitive. Other including 18del L747P have also been responsive dacomitinib. Interestingly, limited studies suggested application certain first third generation tyrosine kinase inhibitors (TKIs)' resistant secondary mutations. Last but not least, both pre-clinical clinical data indicated an encouraging intracranial tumor control ability, regardless mutations.Dacomitinib good disease NSCLC subtypes, selective is considerable this setting, especially those metastases.

Language: Английский

Citations

3
Advancement of regulating cellular signaling pathways in NSCLC target therapy via nanodrug DOI Creative Commons
Wenqiang Li, Mei Li,

Qian Huang

et al.

Frontiers in Chemistry, Journal Year: 2023, Volume and Issue: 11

Published: Sept. 7, 2023

Lung cancer (LC) is one of the leading causes high cancer-associated mortality worldwide. Non-small cell lung (NSCLC) most common type LC. The mechanisms NSCLC evolution involve alterations multiple complex signaling pathways. Even with advances in biological understanding, early diagnosis, therapy, and drug resistance, many dilemmas still need to face treatments. However, efforts have been made explore pathological changes tumor cells based on specific molecular signals for therapy targeted delivery. Nano-delivery has great potential diagnosis treatment tumors. In recent years, studies focused different combinations drugs nanoparticles (NPs) constitute nano-based delivery systems (NDDS), which deliver regulating pathways cells, them positive implications. This review summarized therapeutic targets discovered as well related NDDS, presented future prospects challenges.

Language: Английский

Citations

3