Drug repurposing for cancer therapy

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: April 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.

Language: Английский

---

Tumor acidity: From hallmark of cancer to target of treatment

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: Aug. 29, 2022

Tumor acidity is one of the cancer hallmarks and associated with metabolic reprogramming use glycolysis, which results in a high intracellular lactic acid concentration. Cancer cells avoid stress major by activation expression proton lactate transporters exchangers have an inverted pH gradient (extracellular pHs are alkaline, respectively). The shift tumor acid-base balance promotes proliferation, apoptosis avoidance, invasiveness, metastatic potential, aggressiveness, immune evasion, treatment resistance. For example, weak-base chemotherapeutic agents may substantially reduced cellular uptake capacity due to "ion trapping". Lactic negatively affects functions activated effector T cells, stimulates regulatory them express programmed cell death receptor 1. On other hand, inversion could be weakness that will allow development new promising therapies, such as tumor-targeted pH-sensitive antibodies pH-responsible nanoparticle conjugates anticancer drugs. regulation levels pharmacological inhibition proteins (monocarboxylate transporters, H

Language: Английский

---

Tumor microenvironment-mediated immune tolerance in development and treatment of gastric cancer

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Oct. 20, 2022

Tumor microenvironment is the general term for all non-cancer components and their metabolites in tumor tissue. These include extracellular matrix, fibroblasts, immune cells, endothelial cells. In early stages of tumors, has a suppressor function. As progresses, tolerance induced under action various factors, such that continuously transformed into tumor-promoting microenvironment, which promotes escape. Eventually, cells manifest characteristics malignant proliferation, invasion, metastasis, drug resistance. recent years, stress effects metabolic phenotypic changes innate (such as neutrophils, mast cells), adaptive have been revealed to mediate emerging mechanisms tolerance, providing us with large number therapeutic targets relieve tolerance. Gastric cancer one most common digestive tract malignancies worldwide, whose mortality rate remains high. According latest guidelines, first-line chemotherapy advanced gastric traditional platinum fluorouracil therapy, while immunotherapy extremely limited, including only Human epidermal growth factor receptor 2 (HER-2) programmed death ligand 1 (PD-L1) targeted drugs, benefits are limited. Clinical experiments confirmed cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), vascular (VEGFR) other drugs alone or combination limited efficacy patients cancer, far less than lung colon tumors. The failure mainly related induction cancer. Therefore, solving tumors key success immunotherapy. this study, we summarize inducing promoting formation phenotype well research progress targeting overcome treatment

Language: Английский

---

The roles of epigallocatechin gallate in the tumor microenvironment, metabolic reprogramming, and immunotherapy

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Jan. 29, 2024

Cancer, a disease that modern medicine has not fully understood and conquered, with its high incidence mortality, deprives countless patients of health even life. According to global cancer statistics, there were an estimated 19.3 million new cases nearly 10 deaths in 2020, the age-standardized mortality rates 201.0 100.7 per 100,000, respectively. Although remarkable advancements have been made therapeutic strategies recently, overall prognosis remains optimistic. Consequently, are still many severe challenges be faced difficult problems solved therapy today. Epigallocatechin gallate (EGCG), natural polyphenol extracted from tea leaves, received much attention for antitumor effects. Accumulating investigations confirmed EGCG can inhibit tumorigenesis progression by triggering apoptosis, suppressing proliferation, invasion, migration, altering tumor epigenetic modification, overcoming chemotherapy resistance. Nevertheless, regulatory roles biomolecular mechanisms immune microenvironment, metabolic immunotherapy remain obscure. In this article, we summarized most recent updates about effects on microenvironment (TME), reprogramming, anti-cancer immunotherapy. The results demonstrated promote response cytotoxic lymphocytes dendritic cells (DCs), attenuate immunosuppression myeloid-derived suppressor (MDSCs) T (Tregs), tumor-promoting functions tumor-associated macrophages (TAMs), neutrophils (TANs), various stromal including cancer-associated fibroblasts (CAFs), endothelial (ECs), stellate cells, mesenchymal stem/stromal (MSCs). Additionally, suppress multiple reprogramming pathways, glucose uptake, aerobic glycolysis, glutamine metabolism, fatty acid anabolism, nucleotide synthesis. Finally, EGCG, as immunomodulator checkpoint blockade, enhance immunotherapeutic efficacy may promising candidate conclusion, plays versatile TME which provides novel insights combined

Language: Английский

---

Rational design of a nonclassical liposomal nanoscale drug delivery system for innovative cancer therapy

BMEMat, Journal Year: 2024, Volume and Issue: 2(3)

Published: April 15, 2024

Abstract Advanced drug delivery systems are widely considered to be powerful approaches for treating cancer and many other diseases because of their superior ability improve pharmacokinetics, promote lesion‐targeted efficacy, and/or reduce the toxic effects diverse therapeutics. Owing unique biomimetic structure lipid bilayers surrounding aqueous cavities, liposomes have been found encapsulate various therapeutics, ranging from small molecules with different hydrophobicities biomacromolecules. With advent surface PEGylation, stealth excellent in vivo long‐circulating behaviors generated, thus these extensively explored development liposomal drugs greatly improved pharmacokinetic by functioning as vehicles. Inspired successes clinical practice, recently utilized main building scaffold or coating layers nanoparticulate formulations, which coined nonclassical nanoscale (NDDSs) this review, enable rational design next‐generation nanomedicine. Therefore, after overviewing latest progress conventional liposome‐based nanomedicine, we will introduce NDDSs well innovative treatment strategies. We subsequently provide a critical perspective on future new nanomedicines based rationally designed NDDSs.

Language: Английский

---

A novel cuproptosis-related molecular pattern and its tumor microenvironment characterization in colorectal cancer

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 30, 2022

Cuproptosis, or copper-induced cell death, has been reported as a novel noncanonical form of death in recent times. However, the potential roles cuproptosis alteration tumor clinicopathological features and formation microenvironment (TME) remain unclear. In this study, we comprehensively analyzed cuproptosis-related molecular patterns 1,274 colorectal cancer samples based on 16 regulators. The consensus clustering algorithm was conducted to identify gene signatures. ssGSEA ESTIMATE algorithms were used evaluate enrichment levels infiltrated immune cells scores, respectively. score established assess individuals with principal component analysis expression genes. Three distinct confirmed demonstrated be associated distinguishable biological processes clinical prognosis. Interestingly, three revealed consistent infiltration characterizations: immune-desert, immune-inflamed, immune-excluded. Enhanced survival, activation cells, high purity presented patients low cuproptosisScore, implicating immune-inflamed phenotype. addition, scores linked mutation burden, MSI-H CTLA4 expression, showing higher proportion (IPS). Taken together, our study pattern TME cuproptosisScore will further strengthen understanding feature instruct more personalized immunotherapy schedule cancer.

Language: Английский

---

Emerging Trends in Gastrointestinal Cancer Targeted Therapies: Harnessing Tumor Microenvironment, Immune Factors, and Metabolomics Insights

Gastroenterology, Journal Year: 2024, Volume and Issue: 167(5), P. 867 - 884

Published: May 15, 2024

Language: Английский

---

Therapeutic Immunomodulation in Gastric Cancer

Cancers, Journal Year: 2024, Volume and Issue: 16(3), P. 560 - 560

Published: Jan. 28, 2024

Gastric carcinoma, being one of the most prevalent types solid tumors, has emerged as third leading cause death worldwide. The symptoms gastric cancer (GC) are typically complex, which makes early detection challenging. Immune checkpoint inhibition become new standard targeted therapy for advanced or metastatic GC. It is currently explored in various combinations, both with and without chemotherapy, across multiple therapies clinical trials. Immunotherapy can stimulate immune responses GC patients, to destruction cells. Compared traditional therapies, immunotherapy shown strong effectiveness tolerable toxicity levels. Hence, this innovative approach treatment gained popularity. In review, we have outlined recent advancements GC, including inhibitors, vaccines, vascular endothelial growth factor-A chimeric antigen receptor T-cell therapy. Our current emphasis on examining immunotherapies presently employed settings, addressing existing challenges associated these therapeutic approaches, exploring promising strategies overcome their limitations.

Language: Английский

---

ECHDC2 inhibits the proliferation of gastric cancer cells by binding with NEDD4 to degrade MCCC2 and reduce aerobic glycolysis

Molecular Medicine, Journal Year: 2024, Volume and Issue: 30(1)

Published: May 23, 2024

Abstract Background The Enoyl-CoA hydratase/isomerase family plays a crucial role in the metabolism of tumors, being for maintaining energy balance and biosynthetic needs cancer cells. However, enzymes within this that are pivotal gastric (GC) remain unclear. Methods We employed bioinformatics techniques to identify key GC. expression ECHDC2 its clinical significance were validated through tissue microarray analysis. GC was further assessed using colony formation assays, CCK8 assay, EDU Glucose lactic acid subcutaneous tumor experiments nude mice. mechanism action Western blotting, Co-immunoprecipitation, immunofluorescence experiments. Results Our analysis multiple datasets indicates low is significantly associated with poor prognosis. Overexpression notably inhibits aerobic glycolysis proliferation cells both vivo vitro. Further revealed overexpression suppresses P38 MAPK pathway by inhibiting protein level MCCC2, thereby restraining Ultimately, it discovered promotes ubiquitination subsequent degradation MCCC2 binding NEDD4. Conclusions These findings underscore regulating cells, suggesting as potential therapeutic target

Language: Английский

---

Exosomes play a crucial role in remodeling the tumor microenvironment and in the treatment of gastric cancer

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 13, 2025

Language: Английский

---