Examination of the Functional Relationship between PD-L1 DNA Methylation and mRNA Expression in Non-Small-Cell Lung Cancer DOI Open Access
Tina Vilsbøll,

Nina Dybdal,

Tina Fuglsang Daugaard

et al.

Cancers, Journal Year: 2023, Volume and Issue: 15(6), P. 1909 - 1909

Published: March 22, 2023

Immunotherapy targeting the interaction between programmed cell death protein 1 (PD-1) and death-ligand (PD-L1) is a treatment option for patients with non-small-cell lung cancer (NSCLC). The expression of PD-L1 by NSCLC cells determines effectiveness, but relationship DNA methylation has not been clearly described. We investigated methylation, mRNA expression, in lines tumor biopsies. used clustered regularly interspaced short palindromic repeats-associated 9 (CRISPR-Cas9) to modify genetic contexts endonuclease deficient Cas9 (dCas9) fusions ten-eleven translocation methylcytosine dioxygenase (TET1) (cytosine-5)-methyltransferase 3A (DNMT3A) manipulate methylation. In lines, we identified specific CpG sites levels inversely correlated expression. However, inducing interferon-γ did decrease level these sites, using CRISPR-Cas9, found that directly confer negative regulation. dCas9-TET1 dCas9-DNMT3A could induce hypo- hyper-methylation, respectively, latter conferring showing functional impact biopsies, inverse correlation was weak. conclude there regulatory link since measures are weakly associated, this study highlights need further research before can be implemented as biomarker drug target improve effectiveness PD-1/PD-L1 immunotherapy NSCLC.

Language: Английский

Therapeutic advances of targeting receptor tyrosine kinases in cancer DOI Creative Commons
Ciprian Tomuleasa, Adrian Bogdan Țigu, Raluca Munteanu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Aug. 14, 2024

Abstract Receptor tyrosine kinases (RTKs), a category of transmembrane receptors, have gained significant clinical attention in oncology due to their central role cancer pathogenesis. Genetic alterations, including mutations, amplifications, and overexpression certain RTKs, are critical creating environments conducive tumor development. Following discovery, extensive research has revealed how RTK dysregulation contributes oncogenesis, with many subtypes showing dependency on aberrant signaling for proliferation, survival progression. These findings paved the way targeted therapies that aim inhibit crucial biological pathways cancer. As result, RTKs emerged as primary targets anticancer therapeutic Over past two decades, this led synthesis validation numerous small molecule kinase inhibitors (TKIs), now effectively utilized treating various types. In manuscript we provide comprehensive understanding context We explored alterations specific receptors across different malignancies, special dedicated examination current inhibitors, highlighting potential therapies. By integrating latest evidence, seek elucidate pivotal biology efficacy inhibition promising treatment outcomes.

Language: Английский

Citations

24
PIK3CA mutation as an acquired resistance driver to EGFR-TKIs in non-small cell lung cancer: Clinical challenges and opportunities DOI Creative Commons
Xiaohong Liu,

Wuxuan Mei,

Pengfei Zhang

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: 202, P. 107123 - 107123

Published: March 2, 2024

Epithelial growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have significantly enhanced the treatment outcomes in non-small cell lung cancer (NSCLC) patients harboring EGFR mutations. However, occurrence of acquired resistance to EGFR-TKIs is an unavoidable outcome observed these patients. Disruption PI3K/AKT/mTOR signaling pathway can contribute emergence TKIs cancer. The PIK3CA mutations following with lead against EGFR-TKIs. This review provides overview current perspectives regarding involvement development Furthermore, we outline state-of-the-art therapeutic strategies targeting We highlight role mutation as mechanism EGFR-mutant NSCLC. Crucially, explore PIK3CA-mediated cancer, aiming optimize effectiveness treatment.

Language: Английский

Citations

18
Molecular mechanisms and therapeutic strategies in overcoming chemotherapy resistance in cancer DOI Creative Commons

Yixiang Gu,

Ruifeng Yang, Yang Zhang

et al.

Molecular Biomedicine, Journal Year: 2025, Volume and Issue: 6(1)

Published: Jan. 6, 2025

Cancer remains a leading cause of mortality globally and major health burden, with chemotherapy often serving as the primary therapeutic option for patients advanced-stage disease, partially compensating limitations non-curative treatments. However, emergence resistance significantly limits its efficacy, posing clinical challenge. Moreover, heterogeneity mechanisms across cancer types complicates development universally effective diagnostic approaches. Understanding molecular chemoresistance identifying strategies to overcome it are current research focal points. This review provides comprehensive analysis key underlying resistance, including drug efflux, enhanced DNA damage repair (DDR), apoptosis evasion, epigenetic modifications, altered intracellular metabolism, role stem cells (CSCs). We also examine specific causes in highlight various targets involved resistance. Finally, we discuss aiming at overcoming such combination therapies, targeted treatments, novel delivery systems, while proposing future directions this evolving field. By addressing these barriers, lays foundation more therapies aimed mitigating

Language: Английский

Citations

6
AXL signaling in cancer: from molecular insights to targeted therapies DOI Creative Commons
Monika Yadav, Anuj K. Sharma, Ketki Patne

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 9, 2025

Abstract AXL, a member of the TAM receptor family, has emerged as potential target for advanced-stage human malignancies. It is frequently overexpressed in different cancers and plays significant role various tumor-promoting pathways, including cancer cell proliferation, invasion, metastasis, epithelial–mesenchymal transition (EMT), angiogenesis, stemness, DNA damage response, acquired therapeutic resistance, immunosuppression, inflammatory responses. Beyond oncology, AXL also facilitates viral infections, SARS-CoV-2 Zika highlighting its importance both virology. In preclinical models, small-molecule kinase inhibitors targeting have shown promising anti-tumorigenic potential. This review primarily focuses on induction, regulation biological functions mediating these pathways. We discuss range strategies, recently developed tyrosine (TKIs), monoclonal antibodies, antibody–drug conjugates (ADCs), anti-AXL-CAR, combination therapies. These interventions are being examined clinical studies, offering improved drug sensitivity efficacy. further mechanisms particularly crosstalk between other critical kinases (RTKs) such c-MET, EGFR, HER2/HER3, VEGFR, PDGFR, FLT3. Finally, we highlight key research areas that require exploration to enhance AXL-mediated approaches outcomes.

Language: Английский

Citations

3
Changes of tumor microenvironment in non-small cell lung cancer after TKI treatments DOI Creative Commons
Shanshan Chen, Jingyi Tang, Fen Liu

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: March 6, 2023

Non-small cell lung cancer (NSCLC) is the most common diagnosis, among which epidermal growth factor receptor (EGFR), Kirsten rat sarcoma (KRAS), and anaplastic lymphoma kinase (ALK) mutations are genetic drivers. Their relative tyrosine inhibitors (TKIs) have shown a better response for oncogene-driven NSCLC than chemotherapy. However, development of resistance inevitable following treatments, need new strategy urgently. Although immunotherapy, hot topic therapy, has an excellent other cancers, few responses been presented from existing evidence, including clinical studies. Recently, tumor microenvironment (TME) increasingly thought to be key parameter efficacy treatment such as targeted therapy or while evidence also that TME could affected by multi-factors, TKIs. Here, we discuss changes in after TKI especially EGFR-TKIs, offer information NSCLC.

Language: Английский

Citations

24
Lipid rafts, caveolae, and epidermal growth factor receptor family: friends or foes? DOI Creative Commons
Francesca Ruzzi, Chiara Cappello, Maria Sofia Semprini

et al.

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

Published: Oct. 11, 2024

Lipid rafts are dynamic microdomains enriched with cholesterol and sphingolipids that play critical roles in cellular processes by organizing concentrating specific proteins involved signal transduction. The interplay between lipid rafts, raft-associated caveolae the human epidermal growth factor receptors has significant implications cancer biology, particularly breast gastric therapy resistance. This review examines structural functional characteristics of their involvement EGFR HER2 signaling, impact rafts/CXCL12/CXCR4/HER2 axis on bone metastasis. We also discuss potential targeting caveolin-1 to enhance therapeutic strategies against HER2-positive cancers co-localization trastuzumab or antibody drug conjugates response. Emerging evidence suggests disrupting raft integrity silencing caveolin-1, through several including cholesterol-lowering molecules, can influence availability internalization, enhancing anti-HER2 targeted offering a novel approach counteract resistance improve treatment efficacy.

Language: Английский

Citations

10
Targeting HER3 to overcome EGFR TKI resistance in NSCLC DOI Creative Commons

Qiuqiang Chen,

Gang Jia, Xilin Zhang

et al.

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

Published: Jan. 4, 2024

Receptor tyrosine kinases (RTKs) play a crucial role in cellular signaling and oncogenic progression. Epidermal growth factor receptor kinase inhibitors (EGFR TKIs) have become the standard treatment for advanced non-small cell lung cancer (NSCLC) patients with EGFR-sensitizing mutations, but resistance frequently emerges between 10 to 14 months. A significant this is of human EGFR 3 (HER3), an family member. Despite its significance, effective targeting HER3 still developing. This review aims bridge gap by deeply examining HER3’s pivotal contribution TKI spotlighting emerging HER3-centered therapeutic avenues, including monoclonal antibodies (mAbs), TKIs, antibody-drug conjugates (ADCs). Preliminary results indicate combining HER3-specific treatments TKIs enhances antitumor effects, leading increased objective response rate (ORR) prolonged overall survival (OS) resistant cases. Embracing HER3-targeting therapies represents transformative approach against emphasizes importance further research optimize patient stratification understand mechanisms.

Language: Английский

Citations

9
Emerging clinical applications of single-cell RNA sequencing in oncology DOI
Emily Boxer,

Nisan Feigin,

Roi Tschernichovsky

et al.

Nature Reviews Clinical Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 28, 2025

Language: Английский

Citations

1
Lung Cancer Research and Treatment: Global Perspectives and Strategic Calls to Action DOI
May-Lucie Meyer,

S. Peters,

Tony Mok

et al.

Annals of Oncology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

Citations

7
Umbilical cord mesenchymal stem cells and lung cancer: We should be hopeful or hopeless? DOI
Reza Arefnezhad,

Maryam Helfi,

Rana Okhravijouybari

et al.

Tissue and Cell, Journal Year: 2024, Volume and Issue: 88, P. 102410 - 102410

Published: May 18, 2024

Language: Английский

Citations

6