Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 949, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.ejphar.2023.175699
Keywords
Colorectal cancer; siRNA; RNA interference; Targeted therapy; Gene silencing
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Colorectal cancer is a common and deadly disease, especially among older individuals. Chemotherapy has negative effects on both normal and malignant cells. Various signaling pathways, such as Hh, JAK/STAT, Wnt/beta-catenin, TNF-beta, EGFR/MAPK, PI3K, NF-kappa B, and Notch, are involved in the development of colorectal cancer. This study focuses on innovative siRNA therapies and delivery methods for the safe and effective treatment of colorectal cancer.
Colorectal cancer (CRC) is the third most common cancer and the leading cause of gastrointestinal cancer death. 90% of people diagnosed with colorectal cancer are over the age of 50; nevertheless, the illness is more aggressive among those detected at a younger age. Chemotherapy-based treatment has several adverse effects on both normal and malignant cells. The primary signaling pathways implicated in the advancement of CRC include hedgehog (Hh), janus kinase and signal transducer and activator of transcription (JAK/STAT), Wingless-related integration site (Wnt)/beta-catenin, transforming growth factor-beta (TNF-beta), epidermal growth factor receptor (EGFR)/Mitogen-activated protein kinases (MAPK), phosphoinositide 3-kinase (PI3K), nuclear factor kappa B (NF-kappa B), and Notch. Loss of heterozygosity in tumor suppressor genes like adenomatous polyposis coli, as well as mutation or deletion of genes like p53 and Kirsten rat sarcoma viral oncogene (KRAS), are all responsible for the occurrence of CRC. Novel therapeutic targets linked to these signal-transduction cascades have been identified as a consequence of advances in small interfering RNA (siRNA) treatments. This study focuses on many innovative siRNA therapies and methodologies for delivering siRNA therapeutics to the malignant site safely and effectively for the treatment of CRC. Treatment of CRC using siRNA-associated nanoparticles (NPs) may inhibit the activity of oncogenes and MDR-related genes by targeting a range of signaling mechanisms. This study summarizes several siRNAs targeting signaling molecules, as well as the therapeutic approaches that might be employed to treat CRC in the future.
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