Prognostic Value of PCSK9 Levels in Premenopausal Women at Risk of Breast Cancer—Evidence from a 17-Year Follow-Up Study DOI Open Access
Massimiliano Ruscica, Chiara Macchi, Sara Gandini

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(7), P. 1411 - 1411

Published: April 4, 2024

Background and aim: The involvement of cholesterol in cancer development remains a topic debate, its association with breast has yet to be consistently demonstrated. Considering that circulating levels depend on several concomitant processes, we tested the liability plasma proprotein convertase subtilisin/kexin type 9 (PCSK9), one key regulators levels, as prognostic biomarker context neoplastic events. Methods: Within prospective randomized prevention trial measured baseline PCSK9. A total 235 at-risk premenopausal women were followed up for 17 years. Participants enrolled this placebo-controlled, phase II, double-blind randomly assigned receive either tamoxifen 5 mg/d or fenretinide 200 mg/d, both agents, placebo 2 associations events evaluated through competing risk Cox regression survival models, adjusted randomization strata (5-year Gail ≥ 1.3% vs. intraepithelial neoplasia small invasive favorable prognosis), age, treatment allocation. PCSK9 biomarkers linked assessed blood samples collected at baseline. Results: plasmatic median interquartile range 207 ng/mL 170–252 ng/mL, respectively. Over follow-up period years 89 events, disease-free curves showed hazard ratio 1.002 (95% CI: 0.999–1.005, p = 0.22) compared below ng/mL. No differences between observed. We found negative correlation estradiol (r −0.305), maintained even after partial adjustment BMI age −0.287). Cholesterol 0.266), LDL-C 0.207), non-HDL-C 0.246), remnant 0.233), triglycerides 0.233) also correlated Conclusions: In early-stage cancer, did not appear have role Larger studies are warranted investigating patients different settings.

Language: Английский

Unraveling the link between cholesterol and immune system in cancer: from biological mechanistic insights to clinical evidence. A narrative review DOI
Federica Pecci, Valeria Cognigni, Giulia Claire Giudice

et al.

Critical Reviews in Oncology/Hematology, Journal Year: 2025, Volume and Issue: unknown, P. 104654 - 104654

Published: Feb. 1, 2025

Language: Английский

Citations

1
Drug development advances in human genetics‐based targets DOI Creative Commons
X. Zhang,

Wenjun Yu,

Yan Li

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(2)

Published: Feb. 1, 2024

Drug development is a long and costly process, with high degree of uncertainty from the identification drug target to its market launch. Targeted drugs supported by human genetic evidence are expected enter phase II/III clinical trials or be approved for marketing more quickly, speeding up process. Currently, data technologies such as genome-wide association studies (GWAS), whole-exome sequencing (WES), whole-genome (WGS) have identified validated many potential molecular targets associated diseases. This review describes structure, biology, genetics-based beneficial loss-of-function (LOF) mutation (target mutations that reduce disease incidence) over past decade. The feasibility eight LOF (PCSK9, ANGPTL3, ASGR1, HSD17B13, KHK, CIDEB, GPR75, INHBE) discovery mainly emphasized, their research prospects challenges discussed. In conclusion, we expect this will inspire researchers use genetics genomics support novel therapeutic direction development, which contribute new repurposing.

Language: Английский

Citations

8
Ubiquitination in lipid metabolism reprogramming: implications for pediatric solid tumors DOI Creative Commons
Weixin Zhang,

Yile Xu,

Yapeng Fang

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 30, 2025

Pediatric solid tumors represent a significant subset of childhood cancers, accounting for approximately 60% new diagnoses. Despite advancements in therapeutic strategies, survival rates remain markedly disparate between high-income and resource-limited settings, underscoring the urgent need novel effective treatments. Lipid metabolic reprogramming is fundamental hallmark cancer, driving tumor progression, resistance, immune evasion through enhanced fatty acid uptake, increased de novo lipid synthesis, activated β-oxidation (FAO). Ubiquitination, dynamic post-translational modification mediated by ubiquitin-proteasome system (UPS), plays crucial role regulating metabolism modulating stability activity key enzymes transporters involved cholesterol pathways. This review comprehensively examines complex interplay ubiquitination pediatric tumors. It delineates mechanisms which influences biosynthesis, efflux, synthesis oxidation, thereby facilitating growth survival. Furthermore, identifies potential UPS-mediated targets explores feasibility integrating ubiquitination-based strategies with existing By targeting UPS to disrupt pathways, avenues may emerge enhance treatment efficacy overcome resistance oncology. current knowledge aims provide foundation development innovative, precision medicine approaches improve clinical outcomes children afflicted

Language: Английский

Citations

0
PCSK9 is a passenger gene in head and neck cancer with minimal pathological influence DOI
Hyunji Kim, Dong-Guk Park,

Su‐Jung Choi

et al.

Archives of Oral Biology, Journal Year: 2025, Volume and Issue: unknown, P. 106302 - 106302

Published: May 1, 2025

Language: Английский

Citations

0
Prognostic implications of PCSK9 expression in HER2-positive breast cancer DOI Creative Commons

Zongwen Wu,

D. Wu,

Chengsheng Huang

et al.

ONCOLOGIE, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 11, 2025

Language: Английский

Citations

0
Effects of PCSK9 inhibitors on cancer, diabetes, and cardiovascular diseases DOI
Mojgan Nejabat, Farzin Hadizadeh, Wael Almahmeed

et al.

Drug Discovery Today, Journal Year: 2025, Volume and Issue: unknown, P. 104316 - 104316

Published: Feb. 1, 2025

Language: Английский

Citations

0
Emerging Targets and Therapeutics in Immuno-Oncology: Insights from Landscape Analysis DOI Creative Commons
Kavita A. Iyer, Julian Ivanov,

Rumiana Tenchov

et al.

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(11), P. 8519 - 8544

Published: May 24, 2024

In the ever-evolving landscape of cancer research, immuno-oncology stands as a beacon hope, offering novel avenues for treatment. This study capitalizes on vast repository immuno-oncology-related scientific documents within CAS Content Collection, totaling over 350,000, encompassing journals and patents. Through pioneering approach melding natural language processing with indexing system, we unveil 300 emerging concepts, depicted in comprehensive "Trend Landscape Map". These spanning therapeutic targets, biomarkers, types cancers among others, are hierarchically organized into eight major categories. Delving deeper, our analysis furnishes detailed quantitative metrics showcasing growth trends past three years. Our findings not only provide valuable insights guiding future research endeavors but also underscore merit tapping unparalleled breadth existing information to derive profound insights.

Language: Английский

Citations

2
Inhibition of PCSK9 enhances the anti-hepatocellular carcinoma effects of TCR-T cells and anti-PD-1 immunotherapy DOI Creative Commons
Weikang Xu,

Minli Hu,

Xinyu Lu

et al.

International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(10), P. 3942 - 3955

Published: Jan. 1, 2024

T cells play important roles in antitumor immunity. However, given that the hepatocellular carcinoma (HCC) tumor microenvironment confers resistance to cell-based immunotherapies, novel strategies boost cell-mediated efficacy are urgently needed for treatment of HCC. Here, we show high proprotein convertase subtilisin/kexin type9 (PCSK9) expression was negatively associated with HCC patient's overall survival and markers CD8

Language: Английский

Citations

2
Emerging Targets and Therapeutics in Immuno-Oncology Landscape: Insights from Natural Language Processing Analysis DOI Creative Commons
Kavita A. Iyer, Julian Ivanov,

Rumiana Tenchov

et al.

Published: Dec. 18, 2023

Rapid and sustained growth in the field of immuno-oncology has resulted expansion available scientific literature. Gaining valuable insights establishing deep often hidden meaningful connections such a large body work is need hour. In this report we summarize our findings from novel Natural Language Programming (NLP)-based approach on dataset >350K publications research spanning across two decades (2000-2022) retrieved CAS Content Collection. Our analysis led to identification >300 emerging concepts major categories as therapeutic targets, biomarkers, therapies, types cancer. We present “Trend Landscape Map” possessing layers intricacies – at first glance providing information for identified arranged hierarchically 8 deeper level detailed quantitative metrics over last three years (2020-2022). While immune checkpoint inhibitors (ICIs), antibody-drug conjugates (ADCs) chimeric antigenic receptors (CARs) continue be important immuno-oncology, their have been modest. On other hand, including protein targets TROP2, nectin-4, gasdermins display rapid increase 2020-2022 while absolute number remain low potentially indicative early emergence. Finally, guided by trend landscape analysis, performed substance data leveraging >3.2 million substances Registry potential higher commercial interest protein/peptide sequences rather than small molecules cancer immunotherapy seen with respect patent publications. It hope that subject matter experts' knowledge-guided big based corpus robustly indexed provides comprehensive picture it stands today map serving resource researchers field.

Language: Английский

Citations

2
Prognostic Value of PCSK9 Levels in Premenopausal Women at Risk of Breast Cancer—Evidence from a 17-Year Follow-Up Study DOI Open Access
Massimiliano Ruscica, Chiara Macchi, Sara Gandini

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(7), P. 1411 - 1411

Published: April 4, 2024

Background and aim: The involvement of cholesterol in cancer development remains a topic debate, its association with breast has yet to be consistently demonstrated. Considering that circulating levels depend on several concomitant processes, we tested the liability plasma proprotein convertase subtilisin/kexin type 9 (PCSK9), one key regulators levels, as prognostic biomarker context neoplastic events. Methods: Within prospective randomized prevention trial measured baseline PCSK9. A total 235 at-risk premenopausal women were followed up for 17 years. Participants enrolled this placebo-controlled, phase II, double-blind randomly assigned receive either tamoxifen 5 mg/d or fenretinide 200 mg/d, both agents, placebo 2 associations events evaluated through competing risk Cox regression survival models, adjusted randomization strata (5-year Gail ≥ 1.3% vs. intraepithelial neoplasia small invasive favorable prognosis), age, treatment allocation. PCSK9 biomarkers linked assessed blood samples collected at baseline. Results: plasmatic median interquartile range 207 ng/mL 170–252 ng/mL, respectively. Over follow-up period years 89 events, disease-free curves showed hazard ratio 1.002 (95% CI: 0.999–1.005, p = 0.22) compared below ng/mL. No differences between observed. We found negative correlation estradiol (r −0.305), maintained even after partial adjustment BMI age −0.287). Cholesterol 0.266), LDL-C 0.207), non-HDL-C 0.246), remnant 0.233), triglycerides 0.233) also correlated Conclusions: In early-stage cancer, did not appear have role Larger studies are warranted investigating patients different settings.

Language: Английский

Citations

0