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The genetic architecture of bone metastases: unveiling the role of epigenetic and genetic modifications in drug resistance.

Bone metastases represent frequent and severe complications in various cancers, notably impacting prognosis and quality of life. This review article delves into the genetic and epigenetic mechanisms underpinning drug resistance in bone metastases, a key challenge in effective cancer treatment. The development of drug resistance in cancer can manifest as either intrinsic or acquired, with genetic heterogeneity playing a pivotal role. Intrinsic resistance is often due to pre-existing mutations, while acquired resistance evolves through genetic and epigenetic alterations during treatment. These a

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… Ac-KLF5 maintains the mesenchymal phenotype, promotes tumor growth, and induces docetaxel resistance, which can be mitigated by targeting CXCR4 with plerixafor. These findings highlight the potential of inhibiting Ac-KLF5/CXCR4 signaling to treat chemoresistant bone metastasis in PCa [ 49 ] . … These enzymes metabolize various anticancer agents, including taxanes like docetaxel and paclitaxel, and their expression within tumor cells, influenced by the bone microenvironment, can alter drug efficacy. …

Bone metastasis and pain research through the dual lens of bibliometrics and bioinformatics: knowledge structure, frontiers, and core pathway analysis (2015-2024).

BackgroundCancer-induced bone pain (CIBP) represents a formidable clinical challenge with complex mechanisms, and existing treatments remain unable to effectively control pain in many patients. This study combined bibliometric and bioinformatic approaches to delineate key research trends, principal themes and future directions in the field of bone metastasis and pain research over the past decade (2015-2024).MethodsWe selected 1,822 relevant documents from the Web of Science Core Collection for bibliometric analysis to identify major research characteristics, collaboration networks and emergin

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… Begin | End | Strength | Year | Entity 2015 | 2016 | 7.1332 | 2015 | Solid tumors 2015 | 2016 | 5.3965 | 2015 | Increased survival 2015 | 2016 | 4.9048 | 2015 | Phase ii 2015 | 2016 | 4.9048 | 2015 | Castration-resistant prostate cancer 2016 | 2018 | 5.2168 | 2015 | Docetaxel 2016 | 2017 | 4.7138 | 2015 … 5.0932 | 2015 | Pain management 2022 | 2024 | 6.8469 | 2015 | Spinal metastases 2022 | 2024 | 5.2666 | 2015 | Radiosurgery Early burst terms (2015–2017) primarily included “solid tumors” (strength 7.13), “increased survival” (5.40), “phase ii” (4.90), “castration-resistant prostate cancer” (4.90), “docetaxel …

The Role of Progranulin (PGRN) in the Pathogenesis of Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) represents the most common and aggressive malignant form of brain tumour in adults and is characterized by an extremely poor prognosis with dismal survival rates. Currently, expanding concepts concerning the pathophysiology of GBM are inextricably linked with neuroinflammatory phenomena. On account of this fact, the identification of novel pathomechanisms targeting neuroinflammation seems to be crucial in terms of yielding successful individual therapeutic strategies. In recent years, the pleiotropic growth factor progranulin (PGRN) has attracted significant atten

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… SORT1-targeting agents have recently entered a clinical trial phase regarding thyroid, breast, and ovarian cancer patient populations, where the effects of this adjuvant therapy have been shown to enhance the effect of existing chemotherapy, permitting the targeted entry of a peptide conjugated to docetaxel … The TH1902 Docetaxel Peptide-Drug Conjugate Inhibits Xenografts Growth of Human SORT1-Positive Ovarian and Triple-Negative Breast Cancer Stem-like Cells. Pharmaceutics. 2022;14:1910. doi: 10.3390/pharmaceutics14091910. 160. …

Radionuclide-labelled nanoparticles for cancer combination therapy: a review.

Radionuclide therapy (RT) is widely used to advanced local cancers. However, its therapeutic efficacy is limited to the radiation resistance of cancer cells. Combination therapy aims to circumvent tumor resistance, and the combination of RT with photothermal therapy (PTT), photodynamic therapy (PDT), chemotherapy (CMT), and immunotherapy has shown promising treatment outcomes. Nanotechnology holds promise in advancing combination therapy by integrating multiple therapies on a nanostructure platform. This is due to the increased surface area, passive/active targeting capabilities, high payload

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… Recently, superparamagnetic iron oxide nanoparticles (SPIONs), silica gold nanoshells, carbon nanoparticles, as well as radiopharmaceuticals labelled with radionuclides, 64 Cu labelled liposomes carrying doxorubicin (Dox) and 89 Zr labelled polymeric nanoparticles carrying docetaxel have been used for … In another important clinical case, 89 Zr labelled polymeric nanoparticles carrying docetaxel was used in a clinical study, and it was found that the size of lesion with the highest nanoparticle uptake decreased by 50% after 96 h of treatment [ 19 ]. …

Molecular targets for anticancer therapies in companion animals and humans: what can we learn from each other?

Despite clinical successes in the treatment of some early stage cancers, it is undeniable that novel and innovative approaches are needed to aid in the fight against cancer. Targeted therapies offer the desirable feature of tumor specificity while sparing healthy tissues, thereby minimizing side effects. However, the success rate of translation of these therapies from the preclinical setting to the clinic is dramatically low, highlighting an important point of necessary improvement in the drug development process in the oncology field. The practice of a comparative oncology approach can addres

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… First-line treatment of advanced breast cancer with sunitinib in combination with docetaxel versus docetaxel alone: results of a prospective, randomized phase III study. J Clin Oncol. 2012;30:921–929. doi: 10.1200/JCO.2011.35.7376. 164. …

Communication in the Cancer Microenvironment as a Target for Therapeutic Interventions.

The tumor microenvironment (TME) is a complex system composed of multiple cells, such as non-cancerous fibroblasts, adipocytes, immune and vascular cells, as well as signal molecules and mediators. Tumor cells recruit and reprogram other cells to produce factors that maintain tumor growth. Communication between cancerous and surrounding cells is a two-way process and engages a diverse range of mechanisms that, in consequence, can lead to rapid proliferation, metastasis, and drug resistance, or can serve as a tumors-suppressor, e.g., through tumor-immune cell interaction. Cross-talk within the

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… Corcoran and colleagues showed that in prostate cancer, EVs convey docetaxel resistance [ 78 ]. This phenomenon was also observed in lung, breast, and liver cancers [ 79 , 80 , 81 ]. … Docetaxel-resistance in prostate cancer: Evaluating associated phenotypic changes and potential for resistance transfer via exosomes. PLoS ONE. 2012;7:e50999. doi: 10.1371/journal.pone.0050999. 79. Kong J.N., He Q., Wang G., Dasgupta S., Dinkins M.B., Zhu G., Kim A., Spassieva S., Bieberich E. …

Resveratrol and Tumor Microenvironment: Mechanistic Basis and Therapeutic Targets.

Resveratrol (3,4',5 trihydroxystilbene) is a naturally occurring non-flavonoid polyphenol. It has various pharmacological effects including antioxidant, anti-diabetic, anti-inflammatory and anti-cancer. Many studies have given special attention to different aspects of resveratrol anti-cancer properties and proved its high efficiency in targeting multiple cancer hallmarks. Tumor microenvironment has a critical role in cancer development and progression. Tumor cells coordinate with a cast of normal cells to aid the malignant behavior of cancer. Many cancer supporting players were detected in tum

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… The PIM1 kinase is a critical component of a survival pathway activated by docetaxel and promotes survival of docetaxel-treated prostate cancer cells J. Biol. Chem. 2008 283 20635 20644 10.1074/jbc.M709479200 18426800 PMC3258959 129. Baur J.A. Sinclair D.A. …

Statins: a repurposed drug to fight cancer.

As competitive HMG-CoA reductase (HMGCR) inhibitors, statins not only reduce cholesterol and improve cardiovascular risk, but also exhibit pleiotropic effects that are independent of their lipid-lowering effects. Among them, the anti-cancer properties of statins have attracted much attention and indicated the potential of statins as repurposed drugs for the treatment of cancer. A large number of clinical and epidemiological studies have described the anticancer properties of statins, but the evidence for anticancer effectiveness of statins is inconsistent. It may be that certain molecular subt

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… Iannelli et al. demonstrated the ability of the valproic acid/simvastatin combination to sensitize metastatic castration-resistant prostate cancer cells to docetaxel and to revert docetaxel-resistance through mevalonate pathway/YAP axis modulation using both in vitro and in vivo models [ 299 ]. …

Targeting urological cancers with CAR-T cell therapy: current landscape and future directions.

BACKGROUND: Urological cancers, including renal, bladder, and prostate cancers, are among the most prevalent solid tumors. The success of chimeric antigen receptor (CAR)-T cell therapy in hematologic malignancies has spurred its exploration for treating urological cancers. MAIN BODY: In the past decade, preclinical studies have demonstrated promising antitumor activity of CAR-T cells against urological cancers. Meanwhile, multiple clinical trials are currently underway to evaluate their safety and efficacy. However, significant challenges impede the efficacy of CAR-T cell therapy in urological

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… Combination strategies in prostate cancer Docetaxel was found to significantly strengthen the therapeutic effects of PSMA-CAR-T cells in both prostate cancer xenograft and liver metastasis mouse models, primarily by reducing MDSCs and immune checkpoint molecules in the TME, such as PD-1, CTLA-4 and …

WT1 gene: a potential therapeutic target for multiple cancer treatment strategies.

The Wilms' Tumor 1 (WT1) gene has attracted significant attention in oncological research owing to its involvement in the pathogenesis of a variety of malignancies. Initially identified in association with Wilms' tumor, a pediatric renal carcinoma, WT1 is now recognized for its broader implications in the etiology of multiple cancers, including leukemia, ovarian cancer, and lung cancer. This review offers a comprehensive analysis of the historical development of WT1 research, explores its mechanisms in cancer progression, and assesses its potential as a therapeutic target, with an emphasis on

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… WT1 also alters cellular metabolism and modulates sensitivity to the chemotherapeutic agent docetaxel. These results highlight WT1’s multifaceted role in regulating EMT, tumor metabolism, and treatment response, thereby contributing to cancer progression and therapy resistance [ 118 ]. …

Clinical analysis of lymphoma with malignant solid tumor simultaneously: a retrospective case series.

This study aimed to investigate the clinical features and potential pathogenesis of lymphoma complicated with malignant solid tumors. Clinical data from 35 patients treated at Yantai Yuhuangding Hospital between January 2018 and March 2023 were retrospectively analyzed. Among 1726 lymphoma patients, 35 (2.03%) were found to have solid tumors, including 22 males and 13 females, with a median age of 62 years (range: 49-83 years). The lymphoma subtypes included 14 cases of diffuse large B-cell lymphoma (DLBCL), 8 cases of small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL), 7 cases

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… : rituximab + lenalidomide + gemcitabine + oxaliplatin; BR: rituximab + bendamustine; RCVP: rituximab + cyclophosphamide + vindesine + dexamethasone; RGDP: rituximab + gemcitabine + cisplatin + dexamethasone; SOX: oxaliplatin + tegafur; MTX: methotrexate; RTX: rituximab; CTX: cyclophosphamide; DTX: docetaxel …

New Oncologic Drugs from 2008 to 2023-Differences in Approval and Access between the United States, Europe and Brazil.

IntroductionAdvancements in oncology have revolutionized cancer treatment, with new drugs being approved at different rates worldwide. Our objective was to evaluate the approval of new oncological drugs for solid tumors by the Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the Brazilian Health Regulatory Agency (ANVISA) since 2008.MethodsData were collected from public and online databases by searching for the date of submission, the date of the procedure, the date of approval, clinical indication, and drug characteristics. The distribution was tested using the Sh

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… Pertuzumabe Para o Tratamento do Câncer de Mama HER2-Positivo Metastático em Primeira Linha de Tratamento Associado ao Trastuzumabe e Docetaxel—Relatório de Recomendação Available online: https://www.gov.br/conitec/pt-br/midias/relatorios/2017/relatorio_pertuzumabetrastuzumabe_ca_mama.pdf (accessed on …

Therapeutic Efficacy of Traditional Chinese Medicine Syndrome-Based Formulae to Neuropathic Pain Caused by Chemotherapy.

ObjectiveChemotherapy-induced neuropathic pain (CINP) is a troublesome complication of anti-cancer treatment. The aim of this retrospective study was to investigate the effectiveness of classic Chinese herbal formulae (CHF) Huang Qi Gui Zhi Wu Wu Tang (HQGZWWT) and Dang Gui Si Ni Tang (DGSNT) in the treatment of CINP.Materials and methodsDouleur Neuropathique 4 (DN4) and Functional Assessment of Cancer Therapy-General (FACT-G) questionnaires were rated at baseline and after 3-monthly CHF treatment.ResultsBy searching through our medical records of all the CIPN patients from 2018 to 2019, we id

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… .) | 12 (32.4) TNM stage I | 1 (2.7) II | 11 (29.7) III | 18 (48.6) IV | 7 (18.9) Previous chemotherapy regimen Cisplatin | 10 (27.0) Carboplatin | 4 (10.8) Oxaliplatin | 16 (43.2) Paclitaxel | 7 (18.9) Docetaxel | 4 (10.8) Vincristine | 2 (5.4) Other (thalidomide) | 1 (2.7) Duration of NP 3 mo-1 y | …

The EPICURE study: a pilot prospective cohort study of heterogeneous and massive data integration in metastatic breast cancer patients.

BackgroundBreast cancer is the most common cancer in women and the first cancer concerning mortality. Metastatic breast cancer remains a disease with a poor prognosis and about 30% of women diagnosed with an early stage will have a secondary progression. Metastatic breast cancer is an incurable disease despite significant therapeutic advances in both supportive cares and targeted specific therapies. In the management of a metastatic patient, each clinician follows a highly complex and strictly personal decision making process. It is based on a number of objective and subjective parameters whic

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… Baselga J Cortés J Kim S-B Im S-A Hegg R Im Y-H Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer N Engl J Med 2012 366 2 109 119 10.1056/NEJMoa1113216 22149875 PMC5705202 10. …

Efficacy and tolerability of controlled-release oxycodone for oxaliplatin-induced peripheral neuropathy and the extension of FOLFOX therapy in advanced colorectal cancer patients.

BackgroundThe oxaliplatin-based regimen FOLFOX is widely used to treat patients with advanced colorectal cancer (CRC). However, dose-limiting toxicity after continuous oxaliplatin administration can lead to peripheral neuropathy. Several agents, including opioids, that have been employed to treat oxaliplatin-induced peripheral neuropathy (OIPN) have been examined in clinical settings regarding their protective and therapeutic effects. However, the pharmacotherapy of these agents has not yet been established. Therefore, we investigated the efficacy and tolerability of oxycodone for OIPN and sub

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… These agents include platinum-based compounds (cisplatin, carboplatin, and oxaliplatin), taxanes (paclitaxel and docetaxel), and vinca alkaloids (vincristine and vinblastine). The symptoms of CIPN mostly depend on the involved nerves. …

Development of Targeted Alpha Particle Therapy for Solid Tumors.

Targeted alpha-particle therapy (TAT) aims to selectively deliver radionuclides emitting α-particles (cytotoxic payload) to tumors by chelation to monoclonal antibodies, peptides or small molecules that recognize tumor-associated antigens or cell-surface receptors. Because of the high linear energy transfer (LET) and short range of alpha (α) particles in tissue, cancer cells can be significantly damaged while causing minimal toxicity to surrounding healthy cells. Recent clinical studies have demonstrated the remarkable efficacy of TAT in the treatment of metastatic, castration-resistant prosta

Prodrugs in Oncology: Bioactivation and Impact on Therapeutic Efficacy and Toxicity.

A prodrug is a molecule that lacks pharmacological activity, but upon enzymatic bioactivation, it can generate a therapeutically active molecule. The primary reason behind the design of a prodrug is to help circumvent challenges associated with the physicochemical properties of a drug molecule, such as solubility, absorption, distribution, and instability. Chemotherapy has been at the forefront of cancer treatment for over 70 years due to its ability to target rapidly proliferating tumor cells. However, a major concern with conventional chemotherapy is the lack of selectivity and its associate

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… This study revealed that patients receiving a combination of 5-Fluorouracil, cisplatin, and docetaxel demonstrated clinically significant improvement outcomes compared to patients treated only with cisplatin and 5-Fluorouracil. … City of Hope Medical Center Dose-Reduced Docetaxel with Cyclophosphamide for the Treatment of Vulnerable Older Women with Stage I-III HER2 Negative Breast Cancer, the Dorothy Trial National Library of Medicine Bethesda, MD, USA 2024 27. Iqubal A. Iqubal M.K. Sharma S. Ansari M.A. Najmi A.K. …

Drugging the efferocytosis process: concepts and opportunities.

The daily removal of billions of apoptotic cells in the human body via the process of efferocytosis is essential for homeostasis. To allow for this continuous efferocytosis, rapid phenotypic changes occur in the phagocytes enabling them to engulf and digest the apoptotic cargo. In addition, efferocytosis is actively anti-inflammatory and promotes resolution. Owing to its ubiquitous nature and the sheer volume of cell turnover, efferocytosis is a point of vulnerability. Aberrations in efferocytosis are associated with numerous inflammatory pathologies, including atherosclerosis, cancer and infe

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… NCT04946890 NCT03510104 NCT04762199 NCT04872478 PF-07265807/trial by Pfizer Metastatic solid tumours I NCT04458259 (ref. 134 ) Gene therapy (AAV-mediated delivery) Retinitis pigmentosa I NCT01482195 (refs 220 – 222 ) CD47 Magrolimab/trials by Gilead Sciences (alone or in combination with pembrolizumab/docetaxel … Axl inhibition by bemcentinib could also sensitize cells that have undergone epithelial–mesenchymal transition to a large number of anti-mitotic drugs — particularly docetaxel in vivo 131 . …

Second-Generation Jak2 Inhibitors for Advanced Prostate Cancer: Are We Ready for Clinical Development?

Androgen deprivation therapy (ADT) for metastatic and high-risk prostate cancer (PC) inhibits growth pathways driven by the androgen receptor (AR). Over time, ADT leads to the emergence of lethal castrate-resistant PC (CRPC), which is consistently caused by an acquired ability of tumors to re-activate AR. This has led to the development of second-generation anti-androgens that more effectively antagonize AR, such as enzalutamide (ENZ). However, the resistance of CRPC to ENZ develops rapidly. Studies utilizing preclinical models of PC have established that inhibition of the Jak2-Stat5 signaling

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… The same study showed that AT9283 in combination with Docetaxel induced significant apoptosis at a very low dose (5 nM) compared to a single treatment of the B-NHL cells with either of the compounds. … In vivo mouse xenograft tumors of mantle cell lymphoma treated with AT9283 (15 or 20 mg/kg) plus Docetaxel (10 mg/kg) showed a significant decrease in tumor growth and enhanced survival of the mice [ 180 ]. …

Plant-Derived Natural Products in Cancer Research: Extraction, Mechanism of Action, and Drug Formulation.

Cancer is one of the main causes of death globally and considered as a major challenge for the public health system. The high toxicity and the lack of selectivity of conventional anticancer therapies make the search for alternative treatments a priority. In this review, we describe the main plant-derived natural products used as anticancer agents. Natural sources, extraction methods, anticancer mechanisms, clinical studies, and pharmaceutical formulation are discussed in this review. Studies covered by this review should provide a solid foundation for researchers and physicians to enhance basi

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… In a phase I trial, docetaxel plus curcumin given to patients with advanced breast cancer with dose escalation, showed some improvements such as biological and clinical responses in most patients [ 461 ]. …