Modulation of pancreatic cancer cell sensitivity to FOLFIRINOX through microRNA-mediated regulation of DNA damage

Carotenuto, Pietro; Amato, Francesco; Lampis, Andrea; Rae, Colin; Hedayat, Somaieh; Previdi, Maria C.; Zito, Domenico; Raj, Maya; Guzzardo, Vincenza; Sclafani, Francesco; Lanese, Andrea; Parisi, Claudia; Vicentini, Caterina; Said-Huntingford, Ian; Hahne, Jens C.; Hallsworth, Albert; Kirkin, Vladimir; Young, Kate; Begum, Ruwaida; Wotherspoon, Andrew; Kouvelakis, Kyriakos; Azevedo, Sergio Xavier; Michalarea, Vasiliki; Upstill-Goddard, Rosie; S, Rao; Watkins, David; Starling, Naureen; Sadanandam, Anguraj; Chang, David K.; Biankin, Andrew V.; Jamieson, Nigel B.; Scarpa, Aldo; Cunningham, David; Chau, Ian; Workman, Paul; Fassan, Matteo; Valeri, Nicola; Braconi, Chiara

doi:10.1038/s41467-021-27099-6

Cited by 14 publications

(16 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…No obvious factors other than CEA were found in our study to predict clinical bene ts from FOLFIRINOX. Previously, two predictive biomarkers for FOLFIRINOX had been identi ed; microRNA (MIR1307) and Carboxylesterase 2 may play a key role in modulating of chemosensitivity [27,28]. Additionally, patients harboring DNA damage repair gene mutations including BRCA mutation were reported to have a remarkable response to FOLFIRNOX [29].…”

Section: Discussionmentioning

confidence: 99%

A prospective multicenter phase II study of FOLFIRINOX as a first-line treatment for patients with advanced and recurrent biliary tract cancer

Takahara

Nakai

Isayama

et al. 2022

Preprint

View full text Add to dashboard Cite

Purpose: Given the promising activity and tolerability of FOLFIRINOX as a second-line treatment for advanced biliary tract cancer (BTC), it can be an attractive first-line treatment option as well. Materials and Methods: This is a single-arm, open-label, multicenter phase II study to evaluate the safety and efficacy of FOLFIRINOX as a first-line treatment for patients with advanced BTC. Primary endpoint was progression-free survival (PFS), and the secondary endpoints included overall survival (OS), tumor response and safety. This study defined primary endpoint might be met when the lower limit value of 80% confidence interval [CI] of the median PFS ≥ 6.0 months. Results: Between June 2016 and March 2020, 35 BTC patients (21 intrahepatic, 10 extrahepatic, 2 gallbladder, 2 ampulla) including 26 unresectable and 9 recurrent disease were enrolled. After a median follow-up of 13.9 months, the median PFS and OS were 7.4 (80% CI, 5.5-7.5) and 14.7 (80% CI, 11.8-15.7) months, respectively. Complete response was achieved in 1 (2.9%) and partial response in 10 (28.6%), giving an objective response rate of 31.4% and disease control rate of 74.3%. Major grade 3-4 adverse events included neutropenia (54.3%), leukopenia (34.4%), febrile neutropenia (17.1%), thrombocytopenia (8.6%), cholangitis (8.6%), anemia, nausea, diarrhea, and peripheral sensory neuropathy (2.9% each). Conclusion:.FOLFIRINOX was well tolerable in patients with advanced BTC, however, this study did not meet the primary endpoint to conduct a phase III trial. Thus, further explorations are required to find a subset of patients and/or certain clinical scenario which might be beneficial from FOLFIRINOX.

show abstract

Section: Discussionmentioning

confidence: 99%

A prospective multicenter phase II study of FOLFIRINOX as a first-line treatment for patients with advanced and recurrent biliary tract cancer

Takahara

Nakai

Isayama

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…No obvious factors other than CEA were found in our study to predict clinical benefits from FOLFIRINOX. Previously, two predictive biomarkers for FOLFIRINOX had been identified; microRNA (MIR1307) and Carboxylesterase 2 may play a key role in modulating of chemosensitivity [ 27 , 28 ]. Additionally, patients harboring DNA damage repair gene mutations including BRCA mutation were reported to have a remarkable response to FOLFIRNOX [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

A prospective multicenter phase II study of FOLFIRINOX as a first-line treatment for patients with advanced and recurrent biliary tract cancer

et al. 2022

View full text Add to dashboard Cite

Summary Given the promising activity and tolerability of FOLFIRINOX as a second-line treatment for advanced biliary tract cancer (BTC), it can be an attractive first-line treatment option as well. This is a single-arm, open-label, multicenter phase II study to evaluate the safety and efficacy of FOLFIRINOX as a first-line treatment for patients with advanced BTC. Primary endpoint was progression-free survival (PFS), and the secondary endpoints included overall survival (OS), tumor response and safety. This study defined primary endpoint might be met when the lower limit value of 80% confidence interval [CI] of the median PFS ≥ 6.0 months. Between June 2016 and March 2020, 35 BTC patients (21 intrahepatic, 10 extrahepatic, 2 gallbladder, 2 ampulla) including 26 unresectable and 9 recurrent disease were enrolled. After a median follow-up of 13.9 months, the median PFS and OS were 7.4 (80% CI, 5.5–7.5) and 14.7 (80% CI, 11.8–15.7) months, respectively. Complete response was achieved in 1 (2.9%) and partial response in 10 (28.6%), giving an objective response rate of 31.4% and disease control rate of 74.3%. Major grade 3–4 adverse events included neutropenia (54.3%), leukopenia (34.4%), febrile neutropenia (17.1%), thrombocytopenia (8.6%), cholangitis (8.6%), anemia, nausea, diarrhea, and peripheral sensory neuropathy (2.9% each). FOLFIRINOX was well tolerable in patients with advanced BTC, however, this study did not meet the primary endpoint to conduct a phase III trial. Thus, further explorations are required to find a subset of patients and/or certain clinical scenario which might be beneficial from FOLFIRINOX.

show abstract

“…As a result, a substantial number of patients develop either local recurrences or distant metastases after surgical resection. Even with resection, PAAD has a poor prognosis with a 5-years overall survival rate of less than 10% ( Yang et al, 2020 ; Carotenuto et al, 2021 ). In spite of the tremendous developments in diagnostic tools, surgical approaches, chemotherapy, radiotherapy, and targeted therapy, these approaches can only provide very few survival advantages for PAAD patients ( Brero et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Glycolysis-Related LINC02432/Hsa-miR-98–5p/HK2 Axis Inhibits Ferroptosis and Predicts Immune Infiltration, Tumor Mutation Burden, and Drug Sensitivity in Pancreatic Adenocarcinoma

Tan

Liu

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Pancreatic adenocarcinoma (PAAD) is a malignant cancer with high incidence and mortality. Glycometabolic rearrangements (aerobic glycolysis) is a hallmark of PAAD and contributes to tumorigenesis and progression through numerous mechanisms. This study aimed to identify a novel glycolysis-related lncRNA-miRNA-mRNA ceRNA signature in PAAD and explore its potential molecular function. We first calculated the glycolysis score for each PAAD patient by the ssGSEA algorithm and found that patients with higher hallmark glycolysis scores had poorer prognosis. Subsequently, we obtained a novel glycolysis-related LINC02432/hsa-miR-98–5p/HK2 axis from the TCGA and GEO databases using comprehensive bioinformatics analysis and developed a nomogram to predict overall survival. Furthermore, functional characterization analysis revealed that LINC02432/hsa-miR-98–5p/HK2 axis risk score was negatively correlated with ferroptosis. The tumor immune infiltration analysis suggested positive correlations between ceRNA risk score and infiltrated M0 macrophage levels in PAAD. Correlation analysis found that ceRNA risk scores were positively correlated with four chemokines (CXCL3, CXCL5, CXCL8 and CCL20) and one immune checkpoint gene (SIGLEC15). Meanwhile, tumor mutation burden (TMB), an indicator for predicting response to immunotherapy, was positively correlated with ceRNA risk score. Finally, the drug sensitivity analysis showed that the high-risk score patients might be more sensitive to EGFR, MEK and ERK inhibitors than low-risk score patients. In conclusion, our study suggested that LINC02432/hsa-miR-98–5p/HK2 axis may serve as a novel diagnostic, prognostic, and therapeutic target in PAAD treatment.

show abstract

Modulation of pancreatic cancer cell sensitivity to FOLFIRINOX through microRNA-mediated regulation of DNA damage

Cited by 14 publications

References 49 publications

A prospective multicenter phase II study of FOLFIRINOX as a first-line treatment for patients with advanced and recurrent biliary tract cancer

A prospective multicenter phase II study of FOLFIRINOX as a first-line treatment for patients with advanced and recurrent biliary tract cancer

A prospective multicenter phase II study of FOLFIRINOX as a first-line treatment for patients with advanced and recurrent biliary tract cancer

Glycolysis-Related LINC02432/Hsa-miR-98–5p/HK2 Axis Inhibits Ferroptosis and Predicts Immune Infiltration, Tumor Mutation Burden, and Drug Sensitivity in Pancreatic Adenocarcinoma

Contact Info

Product

Resources

About