Neuroendocrine transdifferentiation in human cancer: molecular mechanisms and therapeutic targets DOI Creative Commons
Jun Jiang, Donghui Han, Jiawei Wang

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(10)

Published: Oct. 1, 2024

Abstract Neuroendocrine transdifferentiation (NEtD), also commonly referred to as lineage plasticity, emerges an acquired resistance mechanism molecular targeted therapies in multiple cancer types, predominately occurs metastatic epidermal growth factor receptor (EGFR)‐mutant non‐small cell lung treated with EGFR tyrosine kinase inhibitors and castration‐resistant prostate androgen targeting therapies. NEtD tumors are the lethal histologic subtype unfavorable prognosis limited treatment. A comprehensive understanding of underlying targeted‐induced plasticity could greatly facilitate development novel In past few years, increasingly elegant studies indicated that share key convergent genomic phenotypic characteristics irrespective their site origin, but embrace distinct change function mechanisms. this review, we provide a overview current regulating NEtD, including genetic alterations, DNA methylation, histone modifications, dysregulated noncoding RNA, lineage‐specific transcription factors regulation, other proteomic alterations. We management clinical preclinical practice.

Language: Английский

EHMT2‐mediated R‐loop formation promotes the malignant progression of prostate cancer via activating Aurora B DOI Creative Commons
Yuyang Zhang,

Mingqin Su,

Yi‐Ming Chen

et al.

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 1, 2025

Abstract Background Chromosomal instability (CIN), a hallmark of cancer, is commonly linked to poor prognosis in high‐grade prostate cancer (PCa). Paradoxically, excessively high levels CIN may impair cell viability. Consequently, understanding how tumours adapt critical for identifying novel therapeutic targets. Methods Bioinformatic analyses were conducted identify genes overexpressed PCa tissues using The Cancer Genome Atlas (TCGA) and GEO datasets. Western blotting immunohistochemistry assays applied determine the expression euchromatic histone lysine methyltransferase 2 (EHMT2), pT232‐Aurora B Cullin 3 (CUL3). proliferation cells was measured through CCK‐8 tests, clonogenesis subcutaneous xenografts human BALB/c nude mice. Live imaging, immunofluorescence (IF) flow cytometry used confirm role EHMT2 mitosis. Co‐immunoprecipitation, IF further elucidated underlying molecular mechanisms. Results highly expressed metastatic exhibiting elevated strongly associated with adverse clinical outcomes patients PCa. Silencing impaired division, inducing G2/M‐phase arrest mitotic catastrophe cells. Mechanistically, indispensable ensure full activation Aurora centromeric R‐loop‐driven ATR–CHK1 pathway, protein peaking during G2/M‐phase. Moreover, CUL3 identified as binding partner EHMT2, mediating its polyubiquitination destabilising levels. Conclusions This study reveals CUL3–EHMT2–Aurora regulatory axis that safeguards accurate chromosome segregation cells, supporting potential application inhibitors. Key points Euchromatic (EHMT2) advanced restraining catastrophic chromosomal (CIN) enhancing fitness. functions via ATR–CHK1–Aurora pathway promote stability. confers enzalutamide resistance activating B. (CUL3) promotes destabilisation deubiquitination.

Language: Английский

Citations

1
Neuroendocrine Transformation as a Mechanism of Resistance to Targeted Lung Cancer Therapies: Emerging Mechanisms and Their Therapeutic Implications DOI Open Access

Asim Joshi,

Neeru Bhaskar,

Joel D. Pearson

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(2), P. 260 - 260

Published: Jan. 15, 2025

Lung cancer is the leading cause of cancer-related deaths worldwide, highlighting a major clinical challenge. broadly classified into two histologically distinct subtypes, termed small cell lung (SCLC) or non-small (NSCLC). Identification various oncogenic drivers NSCLC has facilitated development targeted therapies that have dramatically improved patient outcomes. However, acquired resistance to these common, which ultimately results in relapse. Several on-target and off-target mechanisms been described for NSCLC. One common mechanism histological transformation initial SCLC, highly aggressive form exhibits neuroendocrine histology. This presents significant challenge, since there are very few treatments available relapsed patients. Although phenomenon NSCLC-to-SCLC was almost 20 years ago, only recently we begun understand underlying this therapy-driven response. These recent discoveries will be key identifying novel biomarkers therapeutic strategies improve outcomes patients undergo transformation. Here, highlight advances discuss potential they uncovered target resistance.

Language: Английский

Citations

0
The inhibitory effect of Osthole on A549 lung adenocarcinoma cells and its biomarker DOI Creative Commons

Yinlan Xu,

Lulu Chen, Dong Liu

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 15, 2025

Language: Английский

Citations

0
Mechanism exploration and model construction for small cell transformation in EGFR-mutant lung adenocarcinomas DOI Creative Commons
Yan Li, Tongji Xie, Shouzheng Wang

et al.

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

Published: Oct. 2, 2024

Language: Английский

Citations

1
Overcoming drug resistance through extracellular vesicle-based drug delivery system in cancer treatment DOI Open Access
Long Tai Zheng,

R. S. F. Chang,

B. Liang

et al.

Cancer Drug Resistance, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 12, 2024

Drug resistance is a major challenge in cancer therapy that often leads to treatment failure and disease relapse. Despite advancements chemotherapeutic agents targeted therapies, cancers develop drug resistance, making these treatments ineffective. Extracellular vesicles (EVs) have gained attention for their potential applications delivery because of natural origin, biocompatibility, ability cross biological barriers. Using the unique properties EVs could enhance accumulation at target sites, minimize systemic toxicity, precisely specific cells. Here, we discuss characteristics functionalization EVs, mechanisms engineered overcome resistance. This review provides comprehensive overview EV-based systems overcoming We highlight revolutionize offer promising strategies more effective modalities.

Language: Английский

Citations

1
Neuroendocrine transdifferentiation in human cancer: molecular mechanisms and therapeutic targets DOI Creative Commons
Jun Jiang, Donghui Han, Jiawei Wang

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(10)

Published: Oct. 1, 2024

Abstract Neuroendocrine transdifferentiation (NEtD), also commonly referred to as lineage plasticity, emerges an acquired resistance mechanism molecular targeted therapies in multiple cancer types, predominately occurs metastatic epidermal growth factor receptor (EGFR)‐mutant non‐small cell lung treated with EGFR tyrosine kinase inhibitors and castration‐resistant prostate androgen targeting therapies. NEtD tumors are the lethal histologic subtype unfavorable prognosis limited treatment. A comprehensive understanding of underlying targeted‐induced plasticity could greatly facilitate development novel In past few years, increasingly elegant studies indicated that share key convergent genomic phenotypic characteristics irrespective their site origin, but embrace distinct change function mechanisms. this review, we provide a overview current regulating NEtD, including genetic alterations, DNA methylation, histone modifications, dysregulated noncoding RNA, lineage‐specific transcription factors regulation, other proteomic alterations. We management clinical preclinical practice.

Language: Английский

Citations

0