Elsevier eBooks, Год журнала: 2023, Номер unknown, С. 315 - 349
Опубликована: Янв. 1, 2023
Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)
Опубликована: Апрель 18, 2024
Abstract Cancer, a complex and multifactorial disease, presents significant challenge to global health. Despite advances in surgical, radiotherapeutic immunological approaches, which have improved cancer treatment outcomes, drug therapy continues serve as key therapeutic strategy. However, the clinical efficacy of is often constrained by resistance severe toxic side effects, thus there remains critical need develop novel therapeutics. One promising strategy that has received widespread attention recent years repurposing: identification new applications for existing, clinically approved drugs. Drug repurposing possesses several inherent advantages context since repurposed drugs are typically cost-effective, proven be safe, can significantly expedite development process due their already established safety profiles. In light this, present review offers comprehensive overview various methods employed repurposing, specifically focusing on treat cancer. We describe antitumor properties candidate drugs, discuss detail how they target both hallmarks tumor cells surrounding microenvironment. addition, we examine innovative integrating with nanotechnology enhance topical delivery. also emphasize role play when used part combination regimen. To conclude, outline challenges associated consider future prospects these transitioning into application.
Язык: Английский
Процитировано
115
Journal of Hematology & Oncology, Год журнала: 2025, Номер 18(1)
Опубликована: Янв. 13, 2025
The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, signaling molecules that interact promote growth therapeutic resistance. Elucidating the intricate interactions between cells TME crucial in understanding progression challenges. A critical process induced by epithelial-mesenchymal transition (EMT), wherein epithelial acquire mesenchymal traits, which enhance their motility invasiveness progression. By targeting various components TME, novel investigational strategies aim disrupt TME's contribution EMT, thereby improving efficacy, addressing resistance, offering a nuanced approach therapy. This review scrutinizes key players emphasizing avenues therapeutically components. Moreover, article discusses implications for resistance mechanisms highlights current toward modulation along with potential caveats.
Язык: Английский
Процитировано
19
Molecular Systems Biology, Год журнала: 2025, Номер unknown
Опубликована: Янв. 21, 2025
Язык: Английский
Процитировано
2
Molecular Biology Reports, Год журнала: 2023, Номер 50(9), С. 7667 - 7680
Опубликована: Июль 7, 2023
Antiepileptic drugs are versatile with the potential to be used in functional drug formulations repurposing approaches. In present review, we investigated anticancer properties of antiepileptic and interlinked cancer epileptic pathways. Our focus was primarily on those that have entered clinical trials positive results provided good preclinical studies. Many contributing factors make therapy fail, like resistance, tumor heterogeneity, cost; exploring all alternatives for efficient treatment is important. It crucial find new targets out antitumor molecules from already clinically validated approved utilizing methods. The advancements genomics, proteomics, other computational approaches speed up repurposing. This review summarizes different cancers progression brain. Valproic acid, oxcarbazepine, lacosamide, lamotrigine, levetiracetam showed beneficial outcomes against cancers. might a option adjuvant therapy, but there need investigate further their efficacy trials.
Язык: Английский
Процитировано
15
International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(3), С. 1977 - 1977
Опубликована: Янв. 19, 2023
Pancreatic cancer (PC) is one of the deadliest malignancies, with an increasing incidence and limited response to current therapeutic options. Therefore, more effective low-toxic agents are needed improve PC patients' outcomes. Resveratrol (RSV) a natural polyphenol multiple biological properties, including anticancer effects. In this study, we explored antiproliferative activities newly synthetized RSV analogues in panel cell lines evaluated physicochemical properties most active compound. This derivative exhibited marked effects cells through mechanisms involving DNA damage, apoptosis induction, interference cycle progression, as assessed using flow cytometry immunoblot analysis proteins, PARP cleavage, H2AX phosphorylation. Notably, compound induced consistent reduction subpopulation CD133+EpCAM+ stem-like phenotype, paralleled by dramatic on clonogenicity. Moreover, had negligible toxicity against normal HFF-1 and, thus, good selectivity index values toward lines. Remarkably, its higher lipophilicity stability human plasma, compared RSV, might ensure better permeation along gastrointestinal tract. Our results provide insights into action contributing activity synthetic analogue, supporting potential value search for safe treatment.
Язык: Английский
Процитировано
14
Anti-Cancer Agents in Medicinal Chemistry, Год журнала: 2022, Номер 23(10), С. 1122 - 1144
Опубликована: Май 22, 2022
Abstract: Tumour relapse, chemotherapy resistance, and metastasis continue to be unsolved issues in cancer therapy. A recent approach has been scrutinise drugs used the clinic for other illnesses modify their structure increase selectivity cells. Chloroquine (CQ) hydroxychloroquine (HCQ), known antimalarials, have successfully treated autoimmune neoplastic diseases. CQ HCQ, well-known lysosomotropic agents, induce apoptosis, downregulate autophagy, tumour microenvironment. Moreover, they affect Toll 9/NF-κB receptor pathway, activate stress response pathways, enhance p53 activity CXCR4-CXCL12 expression cells, which would help explain effects treatment. These compounds can normalise tumourassociated vasculature, promote activation of immune system, change phenotype tumour-associated macrophages (from M2 M1), stimulate cancer-associated fibroblasts. We aim review historical aspects its derivatives most relevant mechanisms that support therapeutic use HCQ treatment cancer.
Язык: Английский
Процитировано
19
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Март 25, 2024
Abstract The DNA-damaging agent gemcitabine (GEM) is a first-line treatment for pancreatic cancer but chemoresistance frequently observed. Several clinical trials investigate the efficacy of GEM in combination with targeted drugs including kinase inhibitors experimental evidence such rational often unclear. Here, we phenotypically screened 13 human adenocarcinoma (PDAC) cell lines against 140 and observed strong synergy ATR inhibitor Elimusertib most lines. Dose-dependent phosphoproteome profiling four following DNA damage induction by revealed block response pathway phosphorylated pS468 CHEK1 as underlying mechanism drug synergy. current work provides rationale why inhibition may be useful PDAC patients constitutes rich phenotypic molecular resource further investigating effective combinations.
Язык: Английский
Процитировано
3
ANZ Journal of Surgery, Год журнала: 2025, Номер unknown
Опубликована: Янв. 22, 2025
Abstract Background Metformin is a diabetes medication with anti‐mitotic properties. A narrative review was performed to investigate people using metformin and the risk of developing pancreatic ductal adenocarcinoma (PDAC) as well survival outcomes in established PDAC. Methods Relevant studies on use PDAC were retrieved from PubMed including observational PDAC, randomized controlled trials treatment Results Of 367 searched, 26 fulfilled criteria for this review. not consistently associated reduced However, use, especially higher cumulative doses, some longer patients subgroup resectable more advanced (non‐resectable metastatic) Conclusion may be overall benefits but metastatic subgroup. The evidence date does support routine an adjuvant therapy
Язык: Английский
Процитировано
0
Cancer Management and Research, Год журнала: 2025, Номер Volume 17, С. 429 - 440
Опубликована: Март 1, 2025
Pancreatic cancer (PC) remains one of the most challenging malignancies to treat. Current therapeutic options are unsatisfactory, and there is an urgent need for more effective less toxic drugs improve dismal prognosis PC. In recent years, drug repurposing (DR) has emerged as attractive strategy identify novel treatments PC by leveraging existing approved other indications. Through use electronic medical records, Artificial Intelligence, study metabolic pathways, signalling many approaches, it become much easier in years potential uses old drugs. Although policy, funding research attention this area steadily growing, major challenges efficient patient-centric DR be addressed. These include but not limited regulatory, financial barriers lack coordination collaboration among several sectors stakeholders. To explore opportunities associated with PC, a one-day multi-stakeholder meeting was held on 14th November 2024 Brussels, Belgium part REMEDi4ALL project. This provided platform researchers, clinicians, industry representatives, funders, regulatory experts, patient advocates discuss propose actions optimize accelerate Insights from support enhance treatment while highlighting importance systemic supportive changes policy landscapes, interdisciplinary collaboration, data sharing, involvement driving innovation. summary highlights key outcomes recommendations informing future efforts advance initiatives context
Язык: Английский
Процитировано
0
Regenerative Engineering and Translational Medicine, Год журнала: 2025, Номер unknown
Опубликована: Март 17, 2025
Язык: Английский
Процитировано
0