Stress-induced Rab11a-exosomes induce AREG-mediated cetuximab resistance in colorectal cancer DOI Creative Commons
John Mason,

Ewan Marks,

Shih‐Jung Fan

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Дек. 20, 2023

Abstract Exosomes are secreted vesicles made intracellularly in the endosomal system. We have previously shown that exosomes not only late endosomes, but also recycling endosomes marked by monomeric G-protein Rab11a. These vesicles, termed Rab11a-exosomes, preferentially under nutrient stress from several cancer cell types, including HCT116 colorectal (CRC) cells. Rab11a-exosomes particularly potent signalling activities, some mediated Epidermal Growth Factor Receptor (EGFR) ligand, Amphiregulin (AREG). Mutant activating forms of KRAS, a downstream target EGFR, often found advanced CRC. When absent, monoclonal antibodies, such as cetuximab, which EGFR and block effects ligands, AREG, can be administered. Patients, however, inevitably develop resistance to either acquiring KRAS mutations or via non-genetic microenvironmental changes. Here we show CRC lines causes release AREG-carrying Rab11a-exosomes. demonstrate while soluble AREG has no effect, much lower levels bound cetuximab-resistant KRAS-mutant cells, suppress cetuximab on KRAS-wild type Caco-2 Using neutralising anti-AREG antibodies an intracellular kinase inhibitor, this effect is activation transfer activated KRAS. Therefore, presentation affects its ability compete with cetuximab. propose Rab11a-exosome-mediated mechanism contributes establishment cetuximab-sensitive cells may explain why tumours carry mutant Graphical This study highlights clinically relevant stress-induced carrying (AREG) drug between genetically distinct Resistance anti-EGFR therapy, passed drug-resistant drug-responsive Unlike Rab11a-exosome-associated competes activate promote EGFR-dependent outcomes, growth. support co-operative evolution clonal heterogeneity during tumour progression.

Язык: Английский

Nanoparticles drug delivery for 5-aminolevulinic acid (5-ALA) in photodynamic therapy (PDT) for multiple cancer treatment: a critical review on biosynthesis, detection, and therapeutic applications DOI
Sankha Bhattacharya, Bhupendra G. Prajapati, Sudarshan Singh

и другие.

Journal of Cancer Research and Clinical Oncology, Год журнала: 2023, Номер 149(19), С. 17607 - 17634

Опубликована: Сен. 30, 2023

Язык: Английский

Процитировано

26
Polymeric nanoparticles approach and identification and characterization of novel biomarkers for colon cancer DOI Creative Commons
Devesh U. Kapoor, Rahul Garg,

Mansi Gaur

и другие.

Results in Chemistry, Год журнала: 2023, Номер 6, С. 101167 - 101167

Опубликована: Окт. 14, 2023

The need for novel approaches to the treatment of colon cancer, a common and deadly disease, is universal. In this compilation, we look at how polymeric nanoparticles (Polymeric nanoparticles) could be used treat cancer. Advantages Polymeric in Fig.hting disease include targeted medication administration, enhanced therapy efficacy, fewer adverse effects. Their impact on cancer huge. Drug release miRNA play crucial roles struggle by enabling early identification, individualised strategies, bolstering PONP mechanisms. most up-to-date developments use biomarkers diagnosis prognosis are also discussed. Biomarkers toxicology range from genes epigenomes molecules. Better patient outcomes can expected when conjunction with personalised cytotoxicity assessment. This strategy has potential completely transform care putting needs each first. Combining therapeutic diagnostic capabilities inside single nanoparticle system, drug delivery elevates concept theranostic applications employing method enables toxicological visualise monitor tailored administration. Additional research clinical validation necessary implement these practise. There reason optimistic about future standard medical care.

Язык: Английский

Процитировано

18
A Multi-Omics Overview of Colorectal Cancer to Address Mechanisms of Disease, Metastasis, Patient Disparities and Outcomes DOI Open Access
Guang Yang,

Xi Yu,

Daniel J. Weisenberger

и другие.

Cancers, Год журнала: 2023, Номер 15(11), С. 2934 - 2934

Опубликована: Май 26, 2023

Human colorectal cancer (CRC) is one of the most common malignancies in men and women across globe, albeit CRC incidence mortality shows a substantial racial ethnic disparity, with highest burden African American patients. Even effective screening tools such as colonoscopy diagnostic detection assays, remains health burden. In addition, primary tumors located proximal (right) or distal (left) sides colorectum have been shown to be unique tumor types that require treatment schema. Distal metastases liver other organ systems are major causes Characterizing genomic, epigenomic, transcriptomic proteomic (multi-omics) alterations has led better understanding biology, resulting targeted therapeutic advancements. this regard, molecular-based subgroups developed show correlations patient outcomes. Molecular characterization highlighted similarities differences between tumors; however, our how improve outcomes based on metastasis biology lagging obstacle improving review, we will summarize multi-omics features their groups, subgroups, strategies challenges for

Язык: Английский

Процитировано

14
Microsatellite instability: A potential game-changer in colorectal cancer diagnosis and treatment DOI Creative Commons
R. Shaikh, Sankha Bhattacharya, Bhupendra G. Prajapati

и другие.

Results in Chemistry, Год журнала: 2024, Номер 7, С. 101461 - 101461

Опубликована: Янв. 1, 2024

Colorectal cancer (CRC) is a complicated illness caused by mix of hereditary and environmental factors. It one the most common malignancies worldwide, yet it also curable if detected early. There are three types molecular changes in CRC: chromosomal instability, CpG island methylator phenotype, microsatellite instability (MSI). MSI an uncommon change generated malfunctioning DNA mismatch repair (MMR) system. occurs approximately 15–20% CRC patients. In CRC, has significant prognostic therapeutic implications. MSI-positive patients have better prognosis more likely to react treatment. can be used identify categorise tumours.

Язык: Английский

Процитировано

4
Stress‐induced Rab11a‐exosomes induce amphiregulin‐mediated cetuximab resistance in colorectal cancer DOI Creative Commons
John Mason,

Ewan Marks,

Shih‐Jung Fan

и другие.

Journal of Extracellular Vesicles, Год журнала: 2024, Номер 13(6)

Опубликована: Июнь 1, 2024

Abstract Exosomes are secreted vesicles made intracellularly in the endosomal system. We have previously shown that exosomes not only late endosomes, but also recycling endosomes marked by monomeric G‐protein Rab11a. These vesicles, termed Rab11a‐exosomes, preferentially under nutrient stress from several cancer cell types, including HCT116 colorectal (CRC) cells. Rab11a‐exosomes particularly potent signalling activities, some mediated epidermal growth factor receptor (EGFR) ligand, amphiregulin (AREG). Mutant activating forms of KRAS, a downstream target EGFR, often found advanced CRC. When absent, monoclonal antibodies, such as cetuximab, which EGFR and block effects ligands, AREG, can be administered. Patients, however, inevitably develop resistance to either acquiring KRAS mutations or via non‐genetic microenvironmental changes. Here we show CRC lines causes release AREG‐carrying Rab11a‐exosomes. demonstrate while soluble AREG has no effect, much lower levels bound cetuximab‐resistant KRAS‐mutant cells, suppress cetuximab on KRAS‐wild type Caco‐2 Using neutralising anti‐AREG antibodies an intracellular kinase inhibitor, this effect is activation transfer activated KRAS. Therefore, presentation affects its ability compete with cetuximab. propose Rab11a‐exosome‐mediated mechanism contributes establishment cetuximab‐sensitive cells may explain why tumours carry mutant

Язык: Английский

Процитировано

4
Deciphering microbial and metabolic influences in gastrointestinal diseases-unveiling their roles in gastric cancer, colorectal cancer, and inflammatory bowel disease DOI Creative Commons

D Philip,

Rebecca Hodgkiss,

S Radhakrishnan

и другие.

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Май 16, 2025

Gastrointestinal disorders (GIDs) affect nearly 40% of the global population, with gut microbiome-metabolome interactions playing a crucial role in gastric cancer (GC), colorectal (CRC), and inflammatory bowel disease (IBD). This study aims to investigate how microbial metabolic alterations contribute development assess whether biomarkers identified one could potentially be used predict another, highlighting cross-disease applicability. Microbiome metabolome datasets from Erawijantari et al. (GC: n = 42, Healthy: 54), Franzosa (IBD: 164, 56), Yachida (CRC: 150, 127) were subjected three machine learning algorithms, eXtreme gradient boosting (XGBoost), Random Forest, Least Absolute Shrinkage Selection Operator (LASSO). Feature selection metabolite unique each shared across conditions. A community (MICOM) model simulated growth fluxes, revealing differences between healthy diseased states. Finally, network analysis uncovered clusters associated traits. Combined models demonstrated strong predictive performance, Forest achieving highest Area Under Curve(AUC) scores for GC(0.94[0.83-1.00]), CRC (0.75[0.62-0.86]), IBD (0.93[0.86-0.98]). These then employed analysis, that trained on GC data successfully predicted biomarkers, while optimal performance scores. findings emphasize potential profiling characterization particularly GIDs, advancing biomarker discovery improved diagnostics targeted therapies.

Язык: Английский

Процитировано

0
Investigation of the regulation of EGF signaling by miRNAs, delving into the underlying mechanism and signaling pathways in cancer DOI

Darmadi Darmadi,

Zafar Aminov, Ahmed Hjazi

и другие.

Experimental Cell Research, Год журнала: 2024, Номер 442(2), С. 114267 - 114267

Опубликована: Сен. 21, 2024

Язык: Английский

Процитировано

2
Therapeutic strategies targeting the epidermal growth factor receptor signaling pathway in metastatic colorectal cancer DOI Open Access
Yi Zhou, Shuang Wu,

Fan-Jie Qu

и другие.

World Journal of Gastrointestinal Oncology, Год журнала: 2024, Номер 16(6), С. 2362 - 2367

Опубликована: Июнь 14, 2024

More than 1.9 million new colorectal cancer (CRC) cases and 935000 deaths were estimated to occur worldwide in 2020, representing about one ten deaths. Overall, ranks third incidence, but second mortality. half of the patients are advanced stages at diagnosis. Treatment options complex because heterogeneity patient population, including different molecular subtypes. Treatments have included conventional fluorouracil-based chemotherapy, targeted therapy, immunotherapy, etc. In recent years, with development genetic testing technology, more drugs been applied treatment CRC, which has further prolonged survival metastatic CRC patients.

Язык: Английский

Процитировано

0
Recent Research Progress in Targeted Ther-apy of Metastatic Colorectal Cancer DOI

婷婷 张

Advances in Clinical Medicine, Год журнала: 2023, Номер 13(06), С. 10321 - 10328

Опубликована: Янв. 1, 2023

Язык: Английский

Процитировано

0
Stress-induced Rab11a-exosomes induce AREG-mediated cetuximab resistance in colorectal cancer DOI Creative Commons
John Mason,

Ewan Marks,

Shih‐Jung Fan

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Дек. 20, 2023

Abstract Exosomes are secreted vesicles made intracellularly in the endosomal system. We have previously shown that exosomes not only late endosomes, but also recycling endosomes marked by monomeric G-protein Rab11a. These vesicles, termed Rab11a-exosomes, preferentially under nutrient stress from several cancer cell types, including HCT116 colorectal (CRC) cells. Rab11a-exosomes particularly potent signalling activities, some mediated Epidermal Growth Factor Receptor (EGFR) ligand, Amphiregulin (AREG). Mutant activating forms of KRAS, a downstream target EGFR, often found advanced CRC. When absent, monoclonal antibodies, such as cetuximab, which EGFR and block effects ligands, AREG, can be administered. Patients, however, inevitably develop resistance to either acquiring KRAS mutations or via non-genetic microenvironmental changes. Here we show CRC lines causes release AREG-carrying Rab11a-exosomes. demonstrate while soluble AREG has no effect, much lower levels bound cetuximab-resistant KRAS-mutant cells, suppress cetuximab on KRAS-wild type Caco-2 Using neutralising anti-AREG antibodies an intracellular kinase inhibitor, this effect is activation transfer activated KRAS. Therefore, presentation affects its ability compete with cetuximab. propose Rab11a-exosome-mediated mechanism contributes establishment cetuximab-sensitive cells may explain why tumours carry mutant Graphical This study highlights clinically relevant stress-induced carrying (AREG) drug between genetically distinct Resistance anti-EGFR therapy, passed drug-resistant drug-responsive Unlike Rab11a-exosome-associated competes activate promote EGFR-dependent outcomes, growth. support co-operative evolution clonal heterogeneity during tumour progression.

Язык: Английский

Процитировано

0