Repositioning of Old Drugs for Novel Cancer Therapies: Continuous Therapeutic Perfusion of Aspirin and Oseltamivir Phosphate with Gemcitabine Treatment Disables Tumor Progression, Chemoresistance, and Metastases

Qorri, Bessi; Mokhtari, Reza; Harless, William; Szewczuk, Myron R.

doi:10.3390/cancers14153595

Cited by 5 publications

(6 citation statements)

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“…Considering the inherent chemoresistance, the rapid development of acquired chemoresistance in chemotherapy treatment, and the low effectiveness of cytotoxic treatments in advanced disease stages, innovative and efficient therapies are urgently required. [4,43] A thorough understanding of the genetic origin and tumor microenvironment could help the prognosis, therapy, diagnosis, and prevention of PAAD. Using a number of different methods, such as the accumulation of reactive oxygen species, inhibition of the proteasome, and prevention of angiogenesis, Cu can induce a variety of cell death processes, including apoptosis and autophagy.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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A prognostic and immunotherapy effectiveness model for pancreatic adenocarcinoma based on cuproptosis-related lncRNAs signature

Zhang,

Yu,

Sun

et al. 2023

Medicine

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Pancreatic adenocarcinoma (PAAD) results in one of the deadliest solid tumors with discouraging clinical outcomes. Growing evidence suggests that long non-coding RNAs (lncRNAs) play a crucial role in altering the growth, prognosis, migration, and invasion of pancreatic cancer cells. Cuproptosis is a novel type of cell death induced by copper (Cu) and is associated with mitochondrial respiration during the tricarboxylic acid cycle. However, the relationship between lncRNAs related to cuproptosis and PAAD is poorly studied. In this study, we investigated the association between a signature of cuproptosis-related lncRNAs and the diagnosis of PAAD. Genomic data and clinical information were obtained using the TCGA dataset, while cuproptosis-related genes (CRGs) from previous studies. Co-expression analysis was utilized to identify lncRNAs associated with cuproptosis. We developed and verified a prognostic risk model following a classification of patients into high- and low-risk categories. The prediction capacity of the risk model was assessed using a number of methods including Kaplan–Meier analysis, receiver operating characteristic (ROC) curves, nomograms, and principal component analysis (PCA). Furthermore, differentially expressed genes (DEGs) were used to perform functional enrichment analyses, and to examine the behaviors of various risk groups in terms of immune-related activities and medication sensitivity. We identified 7 cuproptosis-related lncRNA signatures, including CASC19, FAM83A-AS1, AC074099.1, AC007292.2, AC026462.3, AL358944.1, and AC009019.1, as overall survival (OS) predictors. OS and progression-free survival (PFS) showed significant differences among patients in different risk groups. Independent prognostic analysis revealed that the cuproptosis-related lncRNA signatures can independently achieve patient prognosis. The risk model demonstrated strong predictive ability for patient outcomes, as evidenced by ROC curves, nomograms, and PCA. Higher tumor mutation burden (TMB) and lower tumor immune dysfunction and exclusion (TIDE) scores were observed in the high-risk group. Additionally, the low-risk group was hypersensitive to 3 anti-cancer medications, whereas the high-risk group was hypersensitive to one. A prognostic risk model with a good predictive ability based on cuproptosis-related lncRNAs was developed, providing a theoretical basis for personalized treatment and immunotherapeutic responses in pancreatic cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A prognostic and immunotherapy effectiveness model for pancreatic adenocarcinoma based on cuproptosis-related lncRNAs signature

Zhang,

Yu,

Sun

et al. 2023

Medicine

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“…Recently, Qorri et al, [148,149] investigated the therapeutic potential of OP, ASA, and the chemotherapeutic agent gemcitabine (GEM) in pancreatic ductal adenocarcinoma cancer (PDAC) cells. They found that ASA+OP+GEM upended MiaPaCa-2 and PANC-1 pancreatic cell survival mechanisms, including viability, promoting apoptosis, and expressing extra-cellular matrix proteins.…”

Section: Inhibition Of the Neu-1 Complex As A Potential Therapeutic T...mentioning

confidence: 99%

“…In preclinical studies, Qorri et al, [149] reported that a continuous therapeutic targeting of Neu-1 using parenteral perfusion of oseltamivir phosphate (OP) and aspirin (ASA) with gemcitabine (GEM) treatment significantly disrupted tumor progression, critical compensatory signaling mechanisms, EMT program, cancer stem cells (CSC), and metastases in a preclinical mouse model of human pancreatic cancer. In addition, they demonstrated that ASA-and OP-treated xenotumors significantly inhibited the metastatic potential when transferred into animals.…”

Section: Inhibition Of the Neu-1 Complex As A Potential Therapeutic T...mentioning

confidence: 99%

Cannabinoids Transmogrify Cancer Metabolic Phenotype via Epigenetic Reprogramming and a Novel CBD Biased G Protein-Coupled Receptor Signaling Platform

Bunsick

Matsukubo

Szewczuk

2023

Cancers

Self Cite

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The concept of epigenetic reprogramming predicts long-term functional health effects. This reprogramming can be activated by exogenous or endogenous insults, leading to altered healthy and different disease states. The exogenous or endogenous changes that involve developing a roadmap of epigenetic networking, such as drug components on epigenetic imprinting and restoring epigenome patterns laid down during embryonic development, are paramount to establishing youthful cell type and health. This epigenetic landscape is considered one of the hallmarks of cancer. The initiation and progression of cancer are considered to involve epigenetic abnormalities and genetic alterations. Cancer epigenetics have shown extensive reprogramming of every component of the epigenetic machinery in cancer development, including DNA methylation, histone modifications, nucleosome positioning, non-coding RNAs, and microRNA expression. Endocannabinoids are natural lipid molecules whose levels are regulated by specific biosynthetic and degradative enzymes. They bind to and activate two primary cannabinoid receptors, type 1 (CB1) and type 2 (CB2), and together with their metabolizing enzymes, form the endocannabinoid system. This review focuses on the role of cannabinoid receptors CB1 and CB2 signaling in activating numerous receptor tyrosine kinases and Toll-like receptors in the induction of epigenetic landscape alterations in cancer cells, which might transmogrify cancer metabolism and epigenetic reprogramming to a metastatic phenotype. Strategies applied from conception could represent an innovative epigenetic target for preventing and treating human cancer. Here, we describe novel cannabinoid-biased G protein-coupled receptor signaling platforms (GPCR), highlighting putative future perspectives in this field.

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“…This finding may be of significant importance, as it may be the missing link between the anticancer efficacy of NSAIDs and the role of glycosylation in inflammation and sialic acidgenesis [113]. Additionally, the therapeutic targeting of Neu-1 with oseltamivir and aspirin with gemcitabine (GEM) treatment significantly disrupts critical signaling mechanisms, tumor progression, and metastasis in a preclinical mouse model of human pancreatic cancer [114]. The enhanced level of sialic acid was detected in the serum of rosiglitazone-treated diabetic patients and significantly correlated with cardiovascular risk factors.…”

Section: Sialylation and The Efficacy Of Protein Kinase Inhibitors In...mentioning

confidence: 99%

Cell Membrane Sialome: Sialic Acids as Therapeutic Targets and Regulators of Drug Resistance in Human Cancer Management

Jastrząb,

Narejko,

Car

et al. 2023

Cancers

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A cellular sialome is a physiologically active and dynamically changing component of the cell membrane. Sialylation plays a crucial role in tumor progression, and alterations in cellular sialylation patterns have been described as modulators of chemotherapy effectiveness. However, the precise mechanisms through which altered sialylation contributes to drug resistance in cancer are not yet fully understood. This review focuses on the intricate interplay between sialylation and cancer treatment. It presents the role of sialic acids in modulating cell–cell interactions, the extracellular matrix (ECM), and the immunosuppressive processes within the context of cancer. The issue of drug resistance is also discussed, and the mechanisms that involve transporters, the tumor microenvironment, and metabolism are analyzed. The review explores drugs and therapeutic approaches that may induce modifications in sialylation processes with a primary focus on their impact on sialyltransferases or sialidases. Despite advancements in cellular glycobiology and glycoengineering, an interdisciplinary effort is required to decipher and comprehend the biological characteristics and consequences of altered sialylation. Additionally, understanding the modulatory role of sialoglycans in drug sensitivity is crucial to applying this knowledge in clinical practice for the benefit of cancer patients.

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Repositioning of Old Drugs for Novel Cancer Therapies: Continuous Therapeutic Perfusion of Aspirin and Oseltamivir Phosphate with Gemcitabine Treatment Disables Tumor Progression, Chemoresistance, and Metastases

Cited by 5 publications

References 74 publications

A prognostic and immunotherapy effectiveness model for pancreatic adenocarcinoma based on cuproptosis-related lncRNAs signature

A prognostic and immunotherapy effectiveness model for pancreatic adenocarcinoma based on cuproptosis-related lncRNAs signature

Cannabinoids Transmogrify Cancer Metabolic Phenotype via Epigenetic Reprogramming and a Novel CBD Biased G Protein-Coupled Receptor Signaling Platform

Cell Membrane Sialome: Sialic Acids as Therapeutic Targets and Regulators of Drug Resistance in Human Cancer Management

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