The Use of Personalized Medicine in Pancreatic Ductal Adenocarcinoma (PDAC): New Therapeutic Opportunities DOI Creative Commons
Inês Mendes, Nuno Vale

Future Pharmacology, Journal Year: 2024, Volume and Issue: 4(4), P. 934 - 954

Published: Dec. 20, 2024

Pancreatic cancer constitutes a significant cause of cancer-related fatalities, with five-year survival rate only 12%. The most prevalent form this disease is pancreatic ductal adenocarcinoma (PDAC). Given that single therapeutic intervention has proven inadequate for the treatment PDAC, it essential to identify distinct molecular signatures could improve efficacy and alleviate economic burden on patients. Surgery recognized as effective option PDAC; however, small percentage patients are candidates procedure due advanced stage at time diagnosis. In context, we propose explore biology PDAC focus microbiome, epigenetics, genetics. Our objective examine existing knowledge in these areas potential pathways personalized medicine. This approach holds promise advancing our understanding development, progression, resistance standard therapy.

Language: Английский

Transforming pancreaticobiliary cancer treatment: Exploring the frontiers of adoptive cell therapy and cancer vaccines DOI Creative Commons
Nawal Amhis,

Julie Carignan,

Lee‐Hwa Tai

et al.

Deleted Journal, Journal Year: 2024, Volume and Issue: 32(3), P. 200825 - 200825

Published: June 13, 2024

Pancreaticobiliary cancer, encompassing malignancies of both the pancreatic and biliary tract, presents a formidable clinical challenge marked by uniformly bleak prognosis. The asymptomatic nature its early stages often leads to delayed detection, contributing an unfavorable 5-year overall survival rate. Conventional treatment modalities have shown limited efficacy, underscoring urgent need for alternative therapeutic approaches. In recent years, immunotherapy has emerged as promising avenue in fight against pancreaticobiliary cancer. Strategies such vaccines use tumor-infiltrating lymphocytes garnered attention their potential elicit more robust durable responses. This review seeks illuminate landscape emerging immunotherapeutic interventions, offering insights from research perspectives. By deepening our understanding cancer exploring innovative modalities, we aim catalyze improvements patient outcomes quality life.

Language: Английский

Citations

4
Secretory Trefoil Factor 1 (TFF1) promotes gemcitabine resistance through chemokine receptor CXCR4 in Pancreatic Ductal Adenocarcinoma DOI
Ashu Shah, Rahat Jahan, Sophia G. Kisling

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 598, P. 217097 - 217097

Published: July 2, 2024

Language: Английский

Citations

4
Tumor-derived miR-203a-3p potentiates muscle wasting by inducing muscle ferroptosis in pancreatic cancer DOI

Yumeng Hu,

Yifu Hu,

Shaobo Zhang

et al.

Cancer Letters, Journal Year: 2025, Volume and Issue: 614, P. 217523 - 217523

Published: Feb. 6, 2025

Language: Английский

Citations

0
Chlorophyllin exerts synergistic anti-tumor effect with gemcitabine in pancreatic cancer by inducing cuproptosis DOI Creative Commons
Jiaqiang Ren,

Tong Su,

Jiachun Ding

et al.

Molecular Medicine, Journal Year: 2025, Volume and Issue: 31(1)

Published: April 4, 2025

Abstract Pancreatic cancer (PC) has high lethality due to multiple reasons, and its limited response conventional chemotherapy like gemcitabine (GEM) is a non-negligible one. Therefore, our study introduces Chlorophyllin (CHL) as an effective therapeutic candidate enhance the efficacy of GEM. Our results demonstrate that combination CHL GEM exhibits significant synergistic anti-tumor effect by targeting oncogenic processes in PC, including inhibiting cell proliferation, invasion, migration, well inducing apoptosis. Further investigations mechanism have revealed induces cuproptosis PC cells through multifaceted process, involving depleting cellular intracellular glutathione (GSH), increasing reactive oxygen species (ROS) levels, subsequently upregulating HSP70 protein heightened oxidative stress. Additionally, releases free Cu 2+ , binds Ferredoxin 1 (FDX1) protein, ultimately leads oligomerization Dihydrolipoamide S-Acetyltransferase (DLAT) proteins amplify copper toxicity within cells. Moreover, vivo experiments demonstrated effectively inhibits growth subcutaneously transplanted tumors while maintaining favorable biosafety profile. In conclusion, identifies potent enhancer GEM’s effects induction cuproptosis, thus providing novel avenue for patients with PC.

Language: Английский

Citations

0
Gap-App: A Sex-Distinct AI-Based Predictor for Pancreatic Ductal Adenocarcinoma Survival as A Web Application Open to Patients and Physicians DOI Creative Commons
Anuj Ojha, Shujun Zhao, Basil Akpunonu

et al.

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217689 - 217689

Published: April 1, 2025

Language: Английский

Citations

0
Discovery of CMNPD31124 as a novel marine-derived PKMYT1 inhibitor for pancreatic ductal adenocarcinoma therapy: computational and biological insights DOI Creative Commons

Chaojie Huang,

Ting Wang, Rui Chen

et al.

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

Published: April 9, 2025

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers due to its late diagnosis, resistance therapy, and a dismal 5-year survival rate only 12%. Overexpression PKMYT1—a key regulator cell cycle—correlates with poor patient outcomes, making it promising therapeutic target. In this study, we identify CMNPD31124, novel marine-derived indole alkaloid, as potent PKMYT1 inhibitor. Molecular docking revealed that CMNPD31124 has superior binding affinity compared reference compound Cpd 4, forming robust interactions critical residues such CYS-190, TYR-121, GLY-122. dynamics simulations further demonstrated stable conformation dynamic adaptability, Chai-1 modeling supporting covalent mechanism at active site. Importantly, in vitro assays showed exhibits an IC 50 18.6 μM MiaPaCa-2 cells 31.7 BXPC3 cells, while concentrations up 80 did not significantly affect normal pancreatic cells. Despite these results, toxicity predictions indicate potential hepatotoxicity neurotoxicity, highlighting need for structural optimization. This work lays solid foundation rational design inhibitors by integrating computational methods insights from marine natural products.

Language: Английский

Citations

0
Gap-App: A sex-distinct AI-based predictor for pancreatic ductal adenocarcinoma survival as a web application open to patients and physicians DOI Creative Commons
Anuj Ojha, Shujun Zhao, Jian‐Ting Zhang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 6, 2024

Abstract In this study, using RNA-Seq gene expression data and advanced machine learning techniques, we identified distinct profiles between male female pancreatic ductal adenocarcinoma (PDAC) patients. Building upon insight, developed sex-specific 3-year survival predictive models along with a single comprehensive model. These outperformed the general model despite smaller sample sizes. We further refined our by most important features extracted from these initial models. The achieved improved accuracies of 92.62% for males 91.96% females, respectively, versus an accuracy 87.84% model, highlighting value analysis. Based on findings, created Gap-App, web application that enables use individual combined sex information personalized predictions. first online tool aiming to bridge gap complex genomic clinical facilitating more precise individualized cancer care, marks significant advancement in prognosis. study not only underscores importance acknowledging differences prognosis, but also sets stage shift traditional one-size-fits-all targeted medicine. GAP-App service is freely available at www.gap-app.org .

Language: Английский

Citations

0
Sex-Related Differences in Pancreatic Ductal Adenocarcinoma Progression and Response to Therapy DOI Open Access
Jelena Grahovac, Ana Djurić, Miljana Tanić

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 12669 - 12669

Published: Nov. 26, 2024

Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly malignancies with an increasing incidence rate and limited therapeutic options. Biological sex has impact on many aspects PDAC development response to therapy, yet it highly unappreciated in both basic translational research, worryingly clinical trials. In this review, we summarize how biological influences mortality, genetic epigenetic landscapes, anti-tumor immunity, responses hormones, cachexia, efficacy therapy. We highlight importance as a variable discuss implement into preclinical research. These considerations should be use researchers aiming at improving understanding biology developing precision medicine strategies.

Language: Английский

Citations

0
The Use of Personalized Medicine in Pancreatic Ductal Adenocarcinoma (PDAC): New Therapeutic Opportunities DOI Creative Commons
Inês Mendes, Nuno Vale

Future Pharmacology, Journal Year: 2024, Volume and Issue: 4(4), P. 934 - 954

Published: Dec. 20, 2024

Pancreatic cancer constitutes a significant cause of cancer-related fatalities, with five-year survival rate only 12%. The most prevalent form this disease is pancreatic ductal adenocarcinoma (PDAC). Given that single therapeutic intervention has proven inadequate for the treatment PDAC, it essential to identify distinct molecular signatures could improve efficacy and alleviate economic burden on patients. Surgery recognized as effective option PDAC; however, small percentage patients are candidates procedure due advanced stage at time diagnosis. In context, we propose explore biology PDAC focus microbiome, epigenetics, genetics. Our objective examine existing knowledge in these areas potential pathways personalized medicine. This approach holds promise advancing our understanding development, progression, resistance standard therapy.

Language: Английский

Citations

0