Anticancer Drug Discovery Based on Natural Products: From Computational Approaches to Clinical Studies

Biomedicines, Journal Year: 2024, Volume and Issue: 12(1), P. 201 - 201

Published: Jan. 16, 2024

Globally, malignancies cause one out of six mortalities, which is a serious health problem. Cancer therapy has always been challenging, apart from major advances in immunotherapies, stem cell transplantation, targeted therapies, hormonal precision medicine, and palliative care, traditional therapies such as surgery, radiation therapy, chemotherapy. Natural products are integral to the development innovative anticancer drugs cancer research, offering scientific community possibility exploring novel natural compounds against cancers. The role like Vincristine Vinblastine thoroughly implicated management leukemia Hodgkin’s disease. computational method initial key approach drug discovery, among various approaches. This review investigates synergy between techniques, highlights their significance discovery process. transition experimental validation highlighted through vitro vivo studies, with examples betulinic acid withaferin A. path toward therapeutic applications have demonstrated clinical studies silvestrol artemisinin, preclinical investigations trials. article also addresses challenges limitations potential anti-cancer drugs. Moreover, integration deep learning artificial intelligence methods may be useful for enhancing products.

Language: Английский

---

Extracellular Vesicular miRNA in Pancreatic Cancer: From Lab to Therapy

Cancers, Journal Year: 2024, Volume and Issue: 16(12), P. 2179 - 2179

Published: June 8, 2024

Pancreatic cancer is a prevalent lethal gastrointestinal that generally does not show any symptoms until it reaches advanced stages, resulting in high mortality rate. People at risk, such as those with family history or chronic pancreatitis, do have universally accepted screening protocol. Chemotherapy and radiotherapy demonstrate limited effectiveness the management of pancreatic cancer, emphasizing urgent need for innovative therapeutic strategies. Recent studies indicated complex interaction among cells within dynamic microenvironment, comprising extracellular matrix, cancer-associated cells, diverse immune intricately regulates biological characteristics disease. Additionally, mounting evidence suggests EVs play crucial role mediators intercellular communication by transportation different biomolecules, miRNA, proteins, DNA, mRNA, lipids, between heterogeneous cell subpopulations. This mediated significantly impacts multiple aspects pathogenesis, including proliferation, angiogenesis, metastasis, resistance to therapy. In this review, we delve into pivotal EV-associated miRNAs progression, development drug well their potential biomarkers drug-delivery mechanisms cancer.

Language: Английский

---

Comprehensive review of drug resistance in mammalian cancer stem cells: implications for cancer therapy

Cancer Cell International, Journal Year: 2024, Volume and Issue: 24(1)

Published: Dec. 18, 2024

Cancer remains a significant global challenge, and despite the numerous strategies developed to advance cancer therapy, an effective cure for metastatic elusive. A major hurdle in treatment success is ability of cells, particularly stem cells (CSCs), resist therapy. These CSCs possess unique abilities, including self-renewal, differentiation, repair, which drive tumor progression chemotherapy resistance. The resilience linked certain signaling pathways. Tumors with pathway-dependent often develop genetic resistance, whereas those pathway-independent undergo epigenetic changes that affect gene regulation. can evade cytotoxic drugs, radiation, apoptosis by increasing drug efflux transporter activity activating survival mechanisms. Future research should prioritize identification new biomarkers molecules better understand use cutting-edge approaches, such as bioinformatics, genomics, proteomics, nanotechnology, offers potential solutions this challenge. Key include developing targeted therapies, employing nanocarriers precise delivery, focusing on CSC-targeted pathways Wnt, Notch, Hedgehog Additionally, investigating multitarget inhibitors, immunotherapy, nanodrug delivery systems critical overcoming resistance cells.

Language: Английский

---

Recent Progress in Enhanced Cancer Diagnosis, Prognosis, and Monitoring Using a Combined Analysis of the Number of Circulating Tumor Cells (CTCs) and Other Clinical Parameters

Cancers, Journal Year: 2023, Volume and Issue: 15(22), P. 5372 - 5372

Published: Nov. 11, 2023

Analysis of circulating tumor cells (CTCs) holds promise to diagnose cancer or monitor its development. Among the methods, counting CTC numbers in blood samples could be simplest way implement it. Nevertheless, clinical utility has not yet been fully accepted. The reasons due rarity and heterogeneity CTCs that lead misleading results from assays only based on single counts. To address this issue, a feasible direction is combine counts with other data for analysis. Recent studies have demonstrated use new strategy early detection prognosis evaluation cancers, even distinguishment cancers different stages. Overall, approach pave path improve technical problems applications techniques. In review, information relevant CTCs, including their characteristics, counting, technologies enrichment, were first introduced. This was followed by discussing challenges perspectives techniques applications. Finally, advantages recent progress combining parameters discussed.

Language: Английский

---

Integrating CRISPR Technology with Key Genetic Markers in Pancreatic Cancer: A New Frontier in Targeted Therapies

SynBio, Journal Year: 2025, Volume and Issue: 3(1), P. 1 - 1

Published: Jan. 6, 2025

Pancreatic cancer is the result of mutations in crucial genetic markers like KRAS and TP53 that make treatment challenging. This article discusses how CRISPR Cas9 technology can be combined with these to create treatments. allows for alteration or repair mutations, aim restoring gene function blocking cancer-causing pathways. For instance, has potential fix CDKN2A genes restore SMAD4 signaling target oncogene body’s cells. However promising, it may encounters obstacles unintentional effects challenges effectively delivering pancreatic tumor Furthermore, ethical concerns, especially related editing germline, need consideration. As techniques based on advance, there a chance them transform landscape by offering personalized therapies. More studies are needed enhance treatments administered accurately safely through methods targeted testing effectiveness.

Language: Английский

---

Exploring the Role of Gut Microbiota and Probiotics in Acute Pancreatitis: A Comprehensive Review

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3433 - 3433

Published: April 6, 2025

Acute pancreatitis (AP) is a common and potentially severe gastrointestinal condition characterized by acute inflammation of the pancreas. The pathophysiology AP multifactorial intricate, involving cascade events that lead to pancreatic injury systemic inflammation. progression influenced many factors, including genetic predispositions, environmental triggers, immune dysregulation. Recent studies showed critical involvement gut microbiota in shaping response modulating inflammatory processes during AP. This review aims provide comprehensive overview emerging role probiotics We analyzed implication pathogenesis modification an attack. primary goals microbiome-based therapies, which include probiotics, prebiotics, antibiotics, fecal transplantation, enteral nutrition, are alter composition microbial community amount metabolites derived from microbiota. By resetting entire flora or supplementing it with certain beneficial organisms their byproducts, these therapeutic approaches aim eradicate harmful microorganisms, reducing avoiding bacterial translocation potential microbiota-based target for nutrition pre- probiotic supplementation transplantation.

Language: Английский

---

Biological activity and computational analysis of novel acrylonitrile derived benzazoles as potent antiproliferative agents for pancreatic adenocarcinoma with antioxidative properties

Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 147, P. 107326 - 107326

Published: April 6, 2024

Language: Английский

---

DLL3 Is a Prognostic and Potentially Predictive Biomarker for Immunotherapy Linked to PD/PD-L Axis and NOTCH1 in Pancreatic Cancer

Biomedicines, Journal Year: 2023, Volume and Issue: 11(10), P. 2812 - 2812

Published: Oct. 17, 2023

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive neoplasm with very poor patient survival outcomes despite available treatments. There urgent need for new potential treatment options and novel biomarkers these patients. Delta-like canonical Notch ligand 3 (DLL3) interacts the receptor causes inhibition of signaling, which confers a advantage to PDAC cells. Thus, DLL3 expression could affect cell survival, its increase patient’s survival. To test this hypothesis, analysis was conducted using progression-free overall from two independent datasets patients, one mRNA z-score levels other Hscore protein level; both were carried out log-rank plotted Kaplan–Meier curves. at level showed association between high longer (PFS) (OS) Then, we designed retrospective study resected samples. Our primary objective dataset assess relationship PFS OS expression. The secondary assessment provide rationale use anti-DLL3-based treatments in combination immunotherapy that supported by link factors are involved immune checkpoints. analyses revealed protective effect OS. Interestingly, significantly correlated PD-L1/2 negatively NOTCH1. Therefore, be considered biomarker better prognosis resectable patients as well therapeutic response. These facts set testing either alone or combined NOTCH1 inhibitors.

Language: Английский

---

Fat malabsorption in pancreatic cancer: Pathophysiology and management

Nutrition in Clinical Practice, Journal Year: 2024, Volume and Issue: 39(S1)

Published: March 1, 2024

Abstract Exocrine pancreatic insufficiency (EPI) is common in ductal adenocarcinoma (PDAC) and may lead to significant nutrition compromise. In the setting of cancer cachexia gastrointestinal toxicities treatments, untreated (or undertreated) EPI exacerbates weight loss, sarcopenia, micronutrient deficiencies, malnutrition. Together, these complications contribute poor tolerance oncologic therapies negatively impact survival. Treatment PDAC involves addition enzyme replacement therapy, with titration improve symptoms. Medical also be applicable include fat‐soluble vitamin replacement, medium‐chain triglycerides, and, some cases, enteral nutrition. Optimizing status an important adjunct treatment approach quality life overall

Language: Английский

---

Pyrvinium Pamoate Alone and With Gemcitabine Exhibits Anti‐Pancreatic Cancer Activity in 2D and 3D Cell Culture Models

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(23)

Published: Dec. 1, 2024

ABSTRACT Pancreatic cancer is an intractable disease with the worst prognosis of all common cancers. The treatment regimens currently used for pancreatic do not significantly impact patient survival, and therefore, effective strategies are urgently needed. Drug repurposing, which identifies new indications existing approved drugs, has proven to be a desirable approach anti‐cancer drug discovery. Indeed, antihelminthic drug, pyrvinium pamoate, shown promise as anti‐pancreatic drug. However, only mechanism action ascribed this been its ability inhibit mitochondrial function. This study showed, using 2D cell cultures 3D spheroids, that pamoate exhibited short‐ long‐term cytotoxicity, inhibited epithelial‐to‐mesenchymal transition invasion migration. Mechanistically, induced DNA damage, stemness markers PI3K/AKT survival pathway, triggered S‐phase cycle arrest apoptotic autophagic death. Importantly, acted synergistically first‐line gemcitabine, in culture models. provides evidence single agent combination gemcitabine cancer.

Language: Английский

---