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Targetable pathways for drug repurposing in gastric cancer.

Gastric cancer (GC) is both the fifth most common cancer worldwide and the fifth in mortality. Owing to a lack of symptoms in the early stages and unspecific clinical presentation in the later stages, GC is usually diagnosed at advanced stages. This means that only approximately 60% of patients are eligible for curative treatment, and overall, GC patients have a 5-year survival rate of only 28.3%, underscoring the importance of developing new treatment strategies. Drug repurposing involves identifying new therapeutic uses for approved drugs and is a promising strategy for cancer treatment beca

Molecular mechanisms of resveratrol as chemo and radiosensitizer in cancer.

One of the primary diseases that cause death worldwide is cancer. Cancer cells can be intrinsically resistant or acquire resistance to therapies and drugs used for cancer treatment through multiple mechanisms of action that favor cell survival and proliferation, becoming one of the leading causes of treatment failure against cancer. A promising strategy to overcome chemoresistance and radioresistance is the co-administration of anticancer agents and natural compounds with anticancer properties, such as the polyphenolic compound resveratrol (RSV). RSV has been reported to be able to sensitize c

Critical considerations in the administration of antineoplastic therapy for patients with malignant solid tumors undergoing hemodialysis.

Patients with chronic kidney disease exhibit a higher risk of developing malignancies, and among those with end-stage renal disease (ESRD) on dialysis, approximately 7% are diagnosed with new-onset tumors within five years. Patients with ESRD who are receiving antineoplastic treatment exhibit a significantly higher incidence and greater severity of adverse effects associated with antineoplastic agents compared to individuals with normal renal function. This complexity involves multiple factors, including the therapy options and dose adjustment of antineoplastic agents, drug-related toxicities,

Current and Emerging Therapies for Targeting the ERK1/2 & PI3K Pathways in Cancer.

The ERK1/2 and PI3K signaling pathways play important roles in cellular proliferation, survival, differentiation, and metabolism. In cancer, these pathways are frequently dysregulated and overactivated, resulting in poor patient prognosis and resistance to treatment. These pathways are activated by receptor tyrosine kinases and send downstream signals to effectors such as RAS, RAF, MEK, AKT, and mTOR. In this review, we highlight the key components of the ERK1/2 and PI3K pathways, the roles they play in tumor progression, and the development of inhibitors and combination therapies designed to

Chemotherapy-induced peripheral neuropathy in children and adolescent cancer patients.

Brain cancer and leukemia are the most common cancers diagnosed in the pediatric population and are often treated with lifesaving chemotherapy. However, chemotherapy causes severe adverse effects and chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting and debilitating side effect. CIPN can greatly impair quality of life and increases morbidity of pediatric patients with cancer, with the accompanying symptoms frequently remaining underdiagnosed. Little is known about the incidence of CIPN, its impact on the pediatric population, and the underlying pathophysiological mecha

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… While all main classes of chemotherapy agents are known to cause CIPN, vinca alkaloids and platinum compounds are used more commonly in pediatric populations and are highly associated with pediatric CIPN ( Kandula et al., 2016 ). …

Applications of nanotechnologies for miRNA-based cancer therapeutics: current advances and future perspectives.

MicroRNAs (miRNAs) are short (18-25 nt), non-coding, widely conserved RNA molecules responsible for regulating gene expression via sequence-specific post-transcriptional mechanisms. Since the human miRNA transcriptome regulates the expression of a number of tumor suppressors and oncogenes, its dysregulation is associated with the clinical onset of different types of cancer. Despite the fact that numerous therapeutic approaches have been designed in recent years to treat cancer, the complexity of the disease manifested by each patient has prevented the development of a highly effective disease

Fanconi anemia pathway as a prospective target for cancer intervention.

Fanconi anemia (FA) is a recessive genetic disorder caused by biallelic mutations in at least one of 22 FA genes. Beyond its pathological presentation of bone marrow failure and congenital abnormalities, FA is associated with chromosomal abnormality and genomic instability, and thus represents a genetic vulnerability for cancer predisposition. The cancer relevance of the FA pathway is further established with the pervasive occurrence of FA gene alterations in somatic cancers and observations of FA pathway activation-associated chemotherapy resistance. In this article we describe the role of th

Antitumoral Agent-Induced Constipation: A Systematic Review.

BackgroundConstipation is a common symptom in patients receiving antitumoral treatment. The mechanisms underlying antitumoral agent-induced constipation (ATAIC) are poorly defined. This systematic review aimed to analyze and synthesize the available information related to the prevalence, etiology, and treatment of ATAIC.MethodsA systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines was conducted. The review included human studies written in English, French, or Spanish involving patients with cancer and containing information abou

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… Retention of reactive platinum compounds that are still capable of inducing DNA adducts can be found up to 20 years post-treatment with platinum-based agents. …

Capecitabine-Induced Hand-Foot Syndrome With Genital Involvement.

Palmar-plantar erythrodysesthesia, also known as hand-foot syndrome (HFS), is a common dermatologic toxicity of capecitabine. In this report, the case of a 59-year-old man with metastatic pancreatic ductal adenocarcinoma who developed grade 2 HFS with rare genital involvement is described. This case underscores the importance of recognizing atypical genital involvement in HFS to support timely management.

Transforming tumor microenvironments: nanotechnology and gene therapy in cellular signaling and epigenetic insight into chemo-resistance.

Chemoresistance remains the primary cause of cancer treatment failure, yet current understanding remains fragmented across isolated mechanistic studies. This review provides a unified framework linking tumor microenvironment (TME) signaling, epigenetic reprogramming, and nanotherapeutic intervention as an integrated axis driving and potentially reversing chemoresistance. We systematically examine how TME components: hypoxia (HIF-1α pathway), acidosis, cancer-associated fibroblasts (TGF-β/PDGF signaling), and immune cells (NF-κB-mediated immunosuppression) activate signaling cascades that direc

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… Enhanced DNA repair Many chemoresistant tumors upregulate DNA repair pathways, such as nucleotide excision repair (NER) and homologous recombination, aiding in the rapid resolution of DNA damage caused by drugs such as platinum compounds and topoisomerase inhibitors (Fig. 2 ). …

Can Some Anticancer Drugs Be Repurposed to Treat Amyotrophic Lateral Sclerosis? A Brief Narrative Review.

Amyotrophic lateral sclerosis (ALS) is a rare progressive motor neuron disease that, due to its high complexity, still lacks effective treatments. Development of a new drug is a highly costly and time-consuming process, and the repositioning of approved drugs can represent an efficient strategy to provide therapeutic opportunities. This is particularly true for rare diseases, which are characterised by small patient populations and therefore attract little commercial interest. Based on the overlap between the biological background of cancer and neurodegeneration, the repurposing of antineoplas

Ribosome Biogenesis and Function in Cancer: From Mechanisms to Therapy.

Ribosome biogenesis is a highly coordinated, multi-step process that assembles the ribosomal machinery responsible for translating mRNAs into proteins. It begins with the rate-limiting step of RNA polymerase I (Pol I) transcription of the 47S ribosomal RNA (rRNA) genes within a specialised nucleolar region in the nucleus, followed by rRNA processing, modification, and assembly with ribosomal proteins and the 5S rRNA produced by Pol III. The ribosomal subunits are then exported to the cytoplasm to form functional ribosomes. This process is tightly regulated by the PI3K/RAS/MYC oncogenic network

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… Alkylating-like Platinum Compounds Platinum-based compounds such as cisplatin and oxaliplatin have a similar mechanism of action to alkylating agents [ 154 , 155 ]. …

Combination Cancer Therapy and Reference Models for Assessing Drug Synergy in Glioblastoma.

Glioblastoma is currently an incurable disease despite the development of a wide variety of therapeutic approaches, from surgical methods to immunotherapy. In current clinical practice, treatment typically involves a combination of existing methods, often comprising three stages: tumor resection, radiotherapy, and chemotherapy. Modern research offers improved chemotherapy strategies, as well as combinations of chemotherapy with immunotherapy. However, the efficacy of these therapies is profoundly influenced by factors such as tumor and peritumoral heterogeneity, alongside complex molecular sig

How to Treat Melanoma? The Current Status of Innovative Nanotechnological Strategies and the Role of Minimally Invasive Approaches like PTT and PDT.

Melanoma is the most aggressive type of skin cancer, the incidence and mortality of which are increasing worldwide. Its extensive degree of heterogeneity has limited its response to existing therapies. For many years the therapeutic strategies were limited to surgery, radiotherapy, and chemotherapy. Fortunately, advances in knowledge have allowed the development of new therapeutic strategies. Despite the undoubted progress, alternative therapies are still under research. In this context, nanotechnology is also positioned as a strong and promising tool to develop nanosystems that act as drug ca

The Hedgehog-GLI pathway in embryonic development and cancer: implications for pulmonary oncology therapy.

Transcriptional regulation and epigenetic mechanisms closely control gene expression through diverse physiological and pathophysiological processes. These include the development of germ layers and post-natal epithelial cell-tissue differentiation, as well as, involved with the induction, promotion and/or progression of human malignancies. Diverse studies have shed light on the molecular similarities and differences involved in the stages of embryological epithelial development and dedifferentiation processes in malignant tumors of epithelial origin, of which many focus on lung carcinomas. In

Decoding chemotherapy-induced peripheral neuropathy: ion channels, disease models, and future directions.

Chemotherapy-induced peripheral neuropathy (CIPN) is a significant side effect of cancer treatments like paclitaxel and oxaliplatin, impacting patient quality of life (QoL). Despite much research, its underlying mechanisms remain unclear and effective therapies are lacking. This review evaluates whether current experimental models accurately reflect CIPN, emphasizing recent molecular and cellular findings, especially the role of sensory ion channels. We outline limitations of existing models and propose more translational preclinical approaches to better capture disease complexity and patient

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… Platinum compounds (such as cisplatin and oxaliplatin) form DNA crosslinks/adducts in tumor cells halting proliferation ( Bernges and Holler, 1991 ). …

Regulation of immunogenic cell death and potential applications in cancer therapy.

Immunogenic cell death (ICD), a type of regulatory cell death, plays an important role in activating the adaptive immune response. Activation of the tumor-specific immune response is accompanied by the cell surface exposure of calreticulin and heat-shock proteins, the secretion of adenosine triphosphate, and the release of high mobility group box-1. In this review, we summarize and classify the latest types of ICD inducers and their molecular mechanisms, and discuss the effects and potential applications of inducing ICD by chemotherapy drugs, targeted drugs, and oncolytic viruses in clinical r

Lumbar Sympathicolysis Attenuates Refractory Chemotherapy-Induced Peripheral Neuropathy in the Lower Extremities: A Prospective, Real-World Study.

PurposeCurrently, there are limited effective treatment strategies available for refractory chemotherapy-induced peripheral neuropathy (CIPN). Lumbar sympathicolysis is a minimally invasive therapy and may offer an option for CIPN. This single-center, prospective, observational study aimed to evaluate the efficacy and safety of CT-guided lumbar sympathicolysis in alleviating multiple symptoms of refractory CIPN in the lower extremities.MethodsThis single-arm study conducted at Henan Cancer Hospital from September 2022 to July 2024,twenty-five patients with refractory CIPN in both lower extremi

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… Introduction Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most serious toxicity effects caused by chemotherapy agents such as taxanes, platinum compounds, vinca alkaloids, thalidomide, and bortezomib. 1–3 CIPN presents with classic “glove and stocking” neuropathy dominated by sensory …

In Search of a Gold Standard Patient-Reported Outcome Measure for Use in Chemotherapy- Induced Peripheral Neuropathy Clinical Trials.

PurposeTo test a reduced version-CIPN15-of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy scale (QLQ-CIPN20) to establish a possible gold-standard patient-reported outcome measure for chemotherapy-induced peripheral neuropathy (CIPN).MethodsUsing a prospective, longitudinal, case-control design, patients (n = 121) receiving neurotoxic chemotherapy completed the CIPN15 at baseline and 12 weeks and underwent objective neurological assessment using the 5-item Total Neuropathy Score-Clinical (TNSc). He

Drug-induced oxidative stress in cancer treatments: Angel or devil?

Oxidative stress (OS), defined as redox imbalance in favor of oxidant burden, is one of the most significant biological events in cancer progression. Cancer cells generally represent a higher oxidant level, which suggests a dual therapeutic strategy by regulating redox status (i.e., pro-oxidant therapy and/or antioxidant therapy). Indeed, pro-oxidant therapy exhibits a great anti-cancer capability, attributing to a higher oxidant accumulation within cancer cells, whereas antioxidant therapy to restore redox homeostasis has been claimed to fail in several clinical practices. Targeting the redox