An update on cancer stem cell survival pathways involved in chemoresistance in triple-negative breast cancer

Future Oncology, Год журнала: 2025, Номер unknown, С. 1 - 21

Опубликована: Фев. 12, 2025

Triple-negative breast cancer (TNBC) presents a formidable global health challenge, marked by its aggressive behavior and significant treatment resistance. This subtype, devoid of estrogen, progesterone, HER2 receptors, largely relies on stem cells (BCSCs) for progression, metastasis, recurrence. BCSCs, characterized their self-renewal capacity resistance to conventional therapies, exploit key surface markers critical signaling pathways like Wnt, Hedgehog, Notch, TGF-β, PI3K/AKT/mTOR Hippo-YAP/TAZ thrive. Their adaptability is underscored mechanisms including drug efflux enhanced DNA repair, contributing poor prognosis high recurrence rates. The tumor microenvironment (TME) further facilitates BCSC survival through complex interactions with stromal immune cells. Emerging therapeutic strategies targeting BCSCs - ranging from immunotherapy nanoparticle-based delivery systems gene-editing technologies aim disrupt these resistant Additionally, innovative approaches focusing exosome-mediated metabolic reprogramming show promise in overcoming chemoresistance. By elucidating the distinct characteristics role TNBC, researchers are paving way novel treatments that may effectively eradicate resilient cells, mitigate ultimately improve patient outcomes. review highlights urgent need targeted address unique biology pursuit more effective interventions TNBC.

Язык: Английский

---

Pharmacological inhibition of hypoxia induced acidosis employing a CAIX inhibitor sensitizes gemcitabine resistant PDAC cells

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Май 14, 2025

Язык: Английский

---

Repurposing Bilastine antihistamine drug as an anti-cancer metallic drug entity: Synthesis and Single crystal X-ray structure of Metal -based Bilastine and phen {Co(II), Cu(II) & Zn(II)} tailored anticancer chemotherapeutic agents against resistant cancer cells.

Dalton Transactions, Год журнала: 2024, Номер 53(24), С. 10126 - 10141

Опубликована: Янв. 1, 2024

New Bilastine derived metal based drugs have been synthesized and evaluated for their anticancer potential.

Язык: Английский

---

Enhancing PDAC Therapy: Decitabine-Olaparib Synergy Targets KRAS-Dependent Tumors

iScience, Год журнала: 2025, Номер 28(2), С. 111842 - 111842

Опубликована: Янв. 21, 2025

Язык: Английский

---

Molecular Docking Appraisal of Pleurotus ostreatus Phytochemicals as Potential Inhibitors of PI3K/Akt Pathway for Breast Cancer Treatment

Bioinformatics and Biology Insights, Год журнала: 2025, Номер 19

Опубликована: Янв. 1, 2025

Introduction: Breast cancer (BC) is a heterogeneous disease involving network of numerous extracellular signal transduction pathways. The phosphoinositide 3-kinase (PI3K)/serine/threonine kinase (Akt)/mechanistic target rapamycin (mTOR) pathway crucial for understanding the BC development. Phosphoinositide 3-kinase, phosphatase and tensin homolog (PTEN), mTOR, Akt, 3-phosphoinositide-dependent 1 (PDK1), FoxO1, glycogen synthase 3 (GSK-3), mouse double minute 2 (MDM2), H-Ras, proapoptotic B-cell lymphoma (BCL-2) family protein (BAD) proteins are key drivers this potential therapeutic targets. Pleurotus ostreatus an edible mushroom that rich in flavonoids phenols can serve as inhibitors PI3K/Akt/mTOR pathway. Aim: This study evaluated anticancer properties P through structure-based virtual screening 22 biologically active compounds present mushroom. Method: Model optimization was carried out on PI3K, PTEN, PDK1, GSK-3, MDM2, BAD molecular docking compounds/control binding pocket were simulated AutoDock Vina PyRx. drug likeness, pharmacokinetic, pharmacodynamic features prospective leads all anticipated. Result: Several potent selected driver identified from ostreatus. Ellagic acid with affinities −8.0, −8.1, −8.2, −6.2, −7.1 kcal/mol BAD, respectively, had better affinity compared their reference drugs. Likewise, apigenin (−7.8 kcal/mol), chrysin quercetin (−6.4 chlorogenic (−6.2 kcal/mol) to H-Ras proteins, respectively. Conclusion: acid, apigenin, luteolin, quercetin, chrysin, naringenin phytochemicals seen lead molecules due ability strongly bind under Analogs these also be designed

Язык: Английский

---

Neuroprotective insights into epigallocatechin gallate (EGCG) for neurodegenerative disorders

Exploration of neuroscience, Год журнала: 2025, Номер unknown

Опубликована: Фев. 24, 2025

Neurodegenerative disorders, including Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis, are among the most significant health concerns worldwide, characterized by neuronal dysfunction, oxidative stress, neuroinflammation, protein misfolding. Epigallocatechin gallate, a green tea polyphenol, has been reported to possess multifaceted neuroprotective properties. It reduces stress through free radical scavenging, activation of antioxidant enzymes, stabilization mitochondrial function. also inhibits neuroinflammation modulation key signaling pathways. suppresses amyloid-beta aggregation in Alzheimer’s alpha-synuclein fibrillation thus attenuating toxic accumulation. Its activity induction autophagy promotion synaptic plasticity supports survival However, low bioavailability metabolic instability hinder its translation into clinic. Strategies nanoparticle encapsulation, structural modifications, combination therapies being explored overcome these challenges. Future research could establish epigallocatechin gallate as viable candidate for managing neurodegenerative disorders.

Язык: Английский

---

Concept of Targeted Drug Conjugate and Its Application in Reversing Drug Resistance

Journal of Medicinal Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Small-molecule targeted drugs have become the mainstream cancer treatment due to their specific therapy. However, drug resistance inevitably happens patients. Herein, we propose "targeted conjugate (TDC)" concept design that enhance antitumor activity, reduce toxicity, and reverse resistance. Upon this idea, compounds Lapa-603 Lapa-604 were obtained by modifying Pt(II) units with Lapatinib's pharmacophore. Research has found can potently inhibit proliferation of tested cells multiple cell targeting EGFR protein causing severe DNA damage. More importantly, presented higher tumor growth inhibitory efficacy than Lapatinib, Cisplatin, or physical mixtures in both MDA-MB-231 BT474 xenograft models. Our research provided promise for development novel based on TDC effectively overcome stronger activity lower toxicity corresponding combination

Язык: Английский

---

Adjuvant Metronomic Chemotherapy After Surgery in pT1-T2 N0 M0 HER2-Positive and ER/PR-Positive Breast Cancer Plus Targeted Therapy, Anti-Hormonal Therapy, and Radiotherapy, with or Without Immunotherapy: A New Operational Proposal

Cancers, Год журнала: 2025, Номер 17(8), С. 1323 - 1323

Опубликована: Апрель 15, 2025

Breast cancer is the most common and deadly female-specific malignancy in world. Four immunohistochemical subtypes are distinguished: luminal A, B, HER2-positive, triple-negative. In turn, HER2-positive subtype presents two variants depending on status of hormone receptors. The variant that expresses them can benefit from both anti-HER2 anti-hormonal therapy. Today, MCTP finds application maintenance therapy after standard care advanced breast when patient’s clinical condition already seriously compromised by metastatic disease; this context, it used as a first-line treatment, pre-treated subjects, or rescue treatment. Here, use adjuvant oral surgery at an early stage HER-2 hormone-positive local proposed, where effective treatment options available, such (e.g., trastuzumab, pertuzumab), tamoxifen, letrozole), radiotherapy, and, case strong PD-1 positivity, immunotherapy.

Язык: Английский

---

Enhancing PDAC Therapy: Decitabine-Olaparib Synergy Targets KRAS-Dependent Tumors

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июнь 28, 2024

SUMMARY Current chemotherapies provide limited clinical benefits to patients with pancreatic ductal adenocarcinoma (PDAC), partly due the lack of effective biomarkers for personalized therapy. KRAS activating mutations occur in almost 90% PDAC cases, leading a subset tumors d ependent on survival (dKRAS). Assessing dKRAS can be achieved using gene expression signature scores, independent specific mutations, allowing therapies. Previous studies have shown that dKRAS-PDAC cells are more sensitive FDA-approved drug decitabine (DEC), although mechanism remains unclear. While DEC is approved hematological tumors, its repurposing solid poses challenges high-dose side effects. Identifying optimal pharmacological approaches and response crucial successful implementation other tumors. Our investigation revealed low-dose combined PARP inhibitor olaparib (OLA) enhances antitumor activity dKRAS-PDAC. Mechanistically, induces DNA damage activates an ATR/ATM-mediated (DDR), PARP1-mediated repair playing role. Inhibiting OLA activity, even BRCA1/2 wild-type homologous recombination (HR)-proficient but it ineffective KRAS-independent Thus, transcriptomic-based dependency scores effectively predict efficacy Additionally, carrying BRCA2 mutation, OLA’s completely inhibiting metastasis growth compared single-drug treatments. findings support further evaluation DEC+OLA combination therapy PDAC, particularly dKRAS-positive irrespective status. This approach extends benefit beyond BRCA status, addressing limitation targeted Furthermore, we highlight DDR as key action DEC, role regulation, underscoring mode this widely used anticancer drug.

Язык: Английский

---

Molecular Iodine Improves the Efficacy and Reduces the Side Effects of Metronomic Cyclophosphamide Treatment against Mammary Cancer Progression

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(16), С. 8822 - 8822

Опубликована: Авг. 13, 2024

Metronomic chemotherapy with cyclophosphamide (Cpp) has shown promising results in cancer protocols. These lower and prolonged doses have antiangiogenic, pro-cytotoxic, moderate secondary effects. Molecular iodine (I2) reduces the viability of cells and, chemotherapeutic agents, activates antitumoral immune response diminishes side The present work evaluates adjuvant oral I2 Cpp using a murine model mammary cancer. Female Sprague Dawley rats 7,12-dimethylbenzantracene-induced tumors received intraperitoneal (50 70 mg/kg two times/week, iCpp50 iCpp70) (0.03%; 50 mg/Kg; oCpp50) doses. (0.05%, mg/100 mL) oCpp50 were offered drinking water for three weeks. iCpp70 was most efficient dose but generated severe body weight loss hemorrhagic cystitis (HC). prevented loss, exhibited actions Cpp, decreasing tumor growth, canceled HC mechanisms, including decreases vascular endothelial growth factor (VEGF) Survivin expression. + diminished angiogenic signals (CD34, vessel-length, VEGF content) proinflammatory cytokines (interleukin-10 necrosis factor-alpha) increased cytotoxic (lymphocytic infiltration, CD8+ cells, Tbet, interferon-gamma) antioxidant markers (nuclear erythroid factor-2 glutathione peroxidase). enhances effectiveness oCpp, making it compelling candidate clinical protocol.

Язык: Английский

---