Результаты поиска

Development of an Active Chimeric IL13Rα2 ADC for Diffuse Intrinsic Pontine Glioma.

IntroductionDiffuse intrinsic pontine glioma (DIPG) is a rare pediatric brain tumor with a critical unmet need due to the lack of approved, curative interventions available. The interweaving of malignant cells with normal tissue makes surgical extraction essentially impossible, and radiation provides only transient benefit. The recent ONC201 FDA approval, however, suggests DIPG therapy is tractable. Having identified overexpression of IL13Rα2 in DIPG tumor tissue versus normal brain tissue, we investigated binding of commercially available IL13Rα2 monoclonal antibodies. The top candidate antib

Совпадение в полном тексте источника
… The CPT derivative topotecan, delivered through CED, was demonstrated to be tolerable and to extend survival time in glioblastoma multiforme (GBM) tumors in small animal models (mice), large animal models (pigs), and human patients. 12 Moreover, topotecan is toxic to glioma tumor cells and relatively … Tissue distribution and antitumor activity of topotecan delivered by intracerebral clysis in a rat glioma model . Neurosurgery . 2000 ; 47 ( 6 ): 1391 – 1399 . doi: 10.1097/00006123-200012000-00026 11126910 14. Bruce JN , Fine RL , Canoll P , et al. …

In Vivo and In Vitro Pharmacokinetic Studies of a Dual Topoisomerase I/II Inhibitor.

Due to high mortality rates, new and more effective drugs are urgently needed in cancer therapy. The novel dual topoisomerase inhibitor P8-D6, a dimethylaminoethyl-substituted pyridophenanthroline, showed in vitro impressive induction of apoptosis in tumors such as ovarian cancer or multiple myeloma compared to the current standard therapy. The purpose of this study was to investigate its in vitro and in vivo pharmacokinetics and to discover further potential drug candidates. Samples of plasma, various tissues, urine, feces, and cell culture supernatants were examined by HPLC. In addition, the

Совпадение в полном тексте источника
… The mean ratio of metabolite to topotecan was approximately 3%, with P8-D6 to P8-D6 N -oxide metabolites at approximately 1%. … In comparison, orally administered topotecan had a bioavailability of 35%. Therefore, P8-D6 is considered to be sufficiently orally absorbable. …

Phytochemical-Based Nanomedicine for Advanced Cancer Theranostics: Perspectives on Clinical Trials to Clinical Use.

In the current chapter, a new strategic compilation of phytochemicals with potent antitumor properties has been addressed, most importantly focusing on cell cycle arrest and apoptotic signaling mechanism. A promising approach in tumor prevention is to eliminate cancer cells preferably via cell cycle arrest and programmed cell death with lesser harm to neighboring normal cells. Cancer cells have a survival advantage to escape apoptosis and relentlessly divide to proliferate, gearing up the cell cycle process. Recently, the use of phytochemical-derived conjugated chemotherapeutic agents has incr

Совпадение в полном тексте источника
… Topotecan [Hycamtin] Topotecan (Hycamtin) is a camptothecin analog extracted from the tree Camptotheca acuminata Decne (Nyssaceae) bark and is a topoisomerase-I inhibitor. … undergo apoptotic death. 16 Topotecan is either given alone or in combination for the treatment of ovarian and small-cell lung cancers and central nervous system tumors [ NCT00611468 , NCT00382733 , and NCT01492673 ]. …

High-Dose Continuous Infusion Ifosfamide as Effective Palliation in a Patient With Relapsed Ewing Sarcoma With Bone Marrow Infiltration and Severe Thrombocytopenia: A Case Report.

BackgroundEwing sarcoma is a rare primary mesenchymal tumor of the bone that requires an intensive multimodal therapeutic approach. Multidrug chemotherapy regimens are also the backbone for relapsing/recurring Ewing sarcoma treatment, yet when the disease relapses as bone marrow infiltration, combination chemotherapy might be difficult to administer and prognosis is poor.CaseThis report describes the case of a 22-year-old patient with Ewing sarcoma who developed severe pancytopenia due to bone marrow infiltration, and who was treated with high-dose continuous infusion ifosfamide, obtaining bot

Совпадение в полном тексте источника
… High‐dose ifosfamide has been recently demonstrated to be an effective regimen for recurrent disease, with other active regimens being cyclophosphamide and topotecan, temozolomide and irinotecan, and gemcitabine and docetaxel [ 7 ]. … On the other hand, a patient with neuroblastoma did not derive any benefit from combination therapy of standard dose topotecan and cyclophosphamide [ 16 ]. …

DNA Damaging Drugs

Аннотация не предоставлена источником. Откройте карточку для перехода к публикации.

Application and mechanistic research of novel therapeutic strategies in cisplatin-resistant small cell lung cancer.

IntroductionSmall cell lung cancer (SCLC) initially responds well to cisplatin-based chemotherapy, but rapid development of drug resistance limits long-term efficacy and subsequent treatment options. Understanding the multifactorial mechanisms of cisplatin resistance is essential for improving patient outcomes. This review synthesizes recent preclinical and clinical advances, focusing on seven key resistance mechanisms and emerging therapeutic strategies, including immunotherapy, targeted therapy, and novel chemotherapeutic agents.DiscussionCisplatin resistance in SCLC arises through multiple

Совпадение в полном тексте источника
… A phase III trial assessed lurbinectedin plus doxorubicin in 613 patients with relapsed SCLC, compared with topotecan or CAV (cyclophosphamide, doxorubicin, vincristine) control. … Topotecan/cisplatin compared with cisplatin/etoposide as first-line treatment for patients with extensive disease small-cell lung cancer: final results of a randomized phase III trial . …

Wisely frugal: ensuring sustainable funding for novel cancer therapeutics through a budget impact analysis in resource-limited settings.

IntroductionCancer care in Sri Lanka is predominantly provided through its state health system which is free at the point of delivery. We performed a budget impact analysis of novel cancer drugs with a view to enabling better prioritising of their procurement.MethodsMedian survival gain was obtained for each indication of a novel cancer drug by a review of the literature. The direct cost of drug procurement was obtained from the Ministry of Health of Sri Lanka and the cost per life year gained was computed for each indication. Two thresholds - per capita gross domestic product (GDP) per life y

Совпадение в полном тексте источника
… Topotecan in the second line treatment of advanced cervical cancer. Cabazitaxel in the treatment of metastatic castration resistant prostate cancer (post-docetaxel). Fulvestrant in the first and second line treatment of endocrine sensitive metastatic breast cancer. … Pertuzumab | Metastatic HER2+ breast cancer | N Engl J Med 2015; 372:724–734 topotecan | Metastatic cervical cancer second line | J Clin Oncol. 2005 Jul 20;23(21):4626–33 Pembrolizumab | PD1+ metastatic cervical cancer first line treatment in combination with chemotherapy | N Engl J Med 2021; 385:1856 …

Arrhythmias, conduction disorders and sudden cardiac death in cancer patients and survivors: expert opinion of the working groups on cardio-oncology and on electrophysiology of the hellenic cardiac society.

Advances in cancer therapeutics have significantly improved patient survival; however, cardiotoxic effects-including arrhythmias-have emerged as a growing clinical concern. This expert opinion, developed by the Working Groups on Cardio-Oncology and Electrophysiology of the Hellenic Cardiological Society, aims to raise awareness of the increasing burden of arrhythmias in cancer patients and survivors. This document explores the multifactorial etiology of arrhythmias in this population, including patient-related factors, the direct effects of malignancy, and the arrhythmogenic potential of thera

Совпадение в полном тексте источника
… (duvelisib, idelalisib) Proteasome inhibitor (ixazomib) SERM (tamoxifen, toremifene) SERM (tamoxifen) Thalidomide TKI (fostamatinib) Trk inhibitor (Larotrectinib) TS inhibitor (capecitabine) | Common metabolism in CYP2D6 CYP3A4 P-gp/ ABCB1 | Use alternative agent Propranolol | Alkaloid (irinotecan, topotecan … Table 5 Drug-drug interactions between anticancer therapies and anticoagulation therapy [ 41 ] Anticoagulation therapy | Cancer therapeutics | Type of interaction Apixaban | AKL TKI (brigatinib, ceritinib crizontinib, lorlatinib) Alkaloid (irinotecan, topotecan) Alkylating agent (ifosfamide) ANT (etoposide …

Revisiting potential value of antitumor drugs in the treatment of COVID-19.

Since an outbreak started in China in 2019, coronavirus disease 2019 (COVID-19) has rapidly become a worldwide epidemic with high contagiousness and caused mass mortalities of infected cases around the world. Currently, available treatments for COVID-19, including supportive care, respiratory support and antiviral therapy, have shown limited efficacy. Thus, more effective therapeutic modalities are highly warranted. Drug repurposing, as an efficient strategy to explore a potential broader scope of the application of approved drugs beyond their original indications, accelerates the process of d

Совпадение в полном тексте источника
… Recent studies have investigated the effects of topotecan in suppressing excessive inflammatory responses upon SARS-CoV-2 infection. … These results implicate a potential role of topotecan as an anti-inflammatory agent in the treatment of COVID-19. Currently, a clinical trial has been launched to investigate the efficacy of topotecan in relieving hypoxia among patients with COVID-19 ( NCT05083000 ). …

Taxane monotherapy regimens for the treatment of recurrent epithelial ovarian cancer.

BACKGROUND: Ovarian cancer is the seventh most frequent cancer diagnosis worldwide, and the eighth leading cause of cancer mortality. Epithe … , including taxanes, is unclear for women whose epithelial ovarian cancer has recurred. Paclitaxel, topotecan, pegylated liposomal doxorubicin hydrochloride, trabectedin and gemcitabine are all licensed for use in the UK at the discretion of clinicians, following discussion with the women as to potential adverse effects. Taxanes can be given in once-weekly …

Future Options of Molecular-Targeted Therapy in Small Cell Lung Cancer.

Lung cancer is the leading cause of cancer-related deaths worldwide. With a focus on histology, there are two major subtypes: Non-small cell lung cancer (NSCLC) (the more frequent subtype), and small cell lung cancer (SCLC) (the more aggressive one). Even though SCLC, in general, is a chemosensitive malignancy, relapses following induction therapy are frequent. The standard of care treatment of SCLC consists of platinum-based chemotherapy in combination with etoposide that is subsequently enhanced by PD-L1-inhibiting atezolizumab in the extensive-stage disease, as the addition of immune-checkp

Совпадение в полном тексте источника
… However, compared to second-line treatments, topotecan or amrubicin, nivolumab monotherapy application did not result in superior outcomes in SCLC [ 45 ]. … Likewise, a phase II randomized second-line study of linsitinib vs. topotecan in relapsed SCLC failed to show any clinical activity, with a PFS that significantly favored topotecan [ 87 ], see Table 3 . …

Revisiting strategies to target ABC transporter-mediated drug resistance in CNS cancer.

A significant number of anticancer drugs fail to treat primary and metastatic brain tumors primarily because of the complex blood-brain barrier (BBB) and overexpression of ATP-binding cassette (ABC) transporters, which decrease drug penetration into the central nervous system and ultimately into tumors. It is noteworthy that the ABC transporters, ABCB1 [known as P-glycoprotein (P-gp)] and ABCG2 [known as breast cancer resistance protein (BCRP)], are overexpressed in brain tumors, including common gliomas. The co-presence of these transporters may negate the inhibition of either transporter, pa

Совпадение в полном тексте источника
… 1 (ABCB1) 16 – 20 | P-glycoprotein 1 (P-gp) | Neutral and cationic hydrophobic | Alkylating agents: temozolomide (TMZ), procarbazine, and carmustin Tyrosine kinase inhibitors: erlotinib, dasatinib, sunitinib, and sorafenib Anti-microtubule taxanes: paclitaxel and docetaxel Topoisomerase inhibitors: topotecan … Elacridar: Study of Elacridar (GF120918) and oral Topotecan in cancer patients 195 | I | The administration of 100 mg of elacridar with oral topotecan produced complete oral bioavailability of topotecan. The recommended oral dose of topotecan is 2.0 mg daily, times 5, every 21 days. …

Potent molecular-targeted therapies for gastro-entero-pancreatic neuroendocrine carcinoma.

Neuroendocrine neoplasms (NENs), which are characterized by neuroendocrine differentiation, can arise in various organs. NENs have been divided into well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs) based on morphological differentiation, each of which has a distinct etiology, molecular profile, and clinicopathological features. While the majority of NECs originate in the pulmonary organs, extrapulmonary NECs occur most predominantly in the gastro-entero-pancreatic (GEP) system. Although platinum-based chemotherapy is the main therapeut

Совпадение в полном тексте источника
… Based on the preclinical results indicating that the dual inhibition of ATR and topoisomerase I was synergistically cytotoxic in SCLC, a proof-of-concept phase II trial of the ATR inhibitor berzosertib plus topotecan was conducted in the second or latter line of SCLC, which showed an ORR of 36% and a … Given that extrapulmonary SCNECs share a common molecular profile with SCLC [ 4 , 5 , 30 ], the trial was amended to assess the efficacy of berzosertib plus topotecan in extrapulmonary SCNECs. …

Reframing small cell lung cancer: therapeutic lessons from hematologic malignancies.

Small cell lung cancer (SCLC) remains one of the most aggressive malignancies, characterized by rapid proliferation, early metastatic dissemination, and poor long-term survival despite initial sensitivity to therapy. SCLC shares several biologic and therapeutic principles with hematologic malignancies, including lineage state dependence, adaptive resistance through non-genetic plasticity, and emerging susceptibility to antigen-directed immune therapies. Reframing SCLC through this lens provides a conceptual framework for understanding treatment failure and identifying new therapeutic strategie

Совпадение в полном тексте источника
… Efficacy and safety of rovalpituzumab tesirine compared with topotecan as second-line therapy in DLL3-high SCLC: results from the phase 3 TAHOE study . J Thorac Oncol . ( 2021 ) 16 : 1547–58 . doi: 10.1016/j.jtho.2021.02.009 . … Randomized phase 3 study of the anti-disialoganglioside antibody dinutuximab and irinotecan vs irinotecan or topotecan for second-line treatment of small cell lung cancer . Lung Cancer . ( 2022 ) 166 : 135–42 . doi: 10.1016/j.lungcan.2022.03.003 . …

The impact of myelosuppression on quality of life of patients treated with chemotherapy.

Side effects from chemotherapy-induced myelosuppression can negatively affect patients' quality of life (QoL). Neutropenia increases infection risk, and anemia frequently results in debilitating fatigue. Additionally, the bleeding risk associated with thrombocytopenia can lead to fear and anxiety. However, traditional interventions for myelosuppression fall short of the ideal. Granulocyte colony-stimulating factors reduce the risk of severe neutropenia but commonly lead to bone pain. Erythropoiesis-stimulating agents are not always effective and may cause thromboembolic events, while transfusi

Совпадение в полном тексте источника
… In 2021, the US FDA approved trilaciclib to decrease the incidence of chemotherapy-induced myelosuppression in adult patients when administered prior to an etoposide/platinum- or topotecan-containing regimen for extensive-stage small-cell lung cancer (ES-SCLC) [ 17 ]. … In addition, trilaciclib is a prophylactic option to decrease the incidence of anemia and RBC transfusions when administered before platinum/etoposide with or without immune checkpoint inhibitor-containing regimens or a topotecan-containing regimen for ES-SCLC [ 35 ]. …

Nephrotoxicity in cancer treatment: An overview.

Anticancer drug nephrotoxicity is an important and increasing adverse drug event that limits the efficacy of cancer treatment. The kidney is an important elimination pathway for many antineoplastic drugs and their metabolites, which occurs by glomerular filtration and tubular secretion. Chemotherapeutic agents, both conventional cytotoxic agents and molecularly targeted agents, can affect any segment of the nephron including its microvasculature, leading to many clinical manifestations such as proteinuria, hypertension, electrolyte disturbances, glomerulopathy, acute and chronic interstitial n

Совпадение в полном тексте источника
… Finally, there are also in this group irinotecan and topotecan. The former has hepatic metabolism and poor renal excretion[ 51 ]. Although lower renal complications are therefore expected, there are reports of toxicity in patients with preexisting renal impairment even at low doses[ 52 ]. … Topotecan is predominantly cleared by the kidneys, and increased toxicity may be seen in patients with moderate renal insufficiency[ 50 , 53 ]. …

Thymoquinone as a Potential Adjuvant Therapy for Cancer Treatment: Evidence from Preclinical Studies.

Thymoquinone (TQ), the main bioactive component of Nigella sativa, has been found to exhibit anticancer effects in numerous preclinical studies. Due to its multitargeting nature, TQ interferes in a wide range of tumorigenic processes and counteracts carcinogenesis, malignant growth, invasion, migration, and angiogenesis. Moreover, TQ can specifically sensitize tumor cells toward conventional cancer treatments (e.g., radiotherapy, chemotherapy, and immunotherapy) and simultaneously minimize therapy-associated toxic effects in normal cells. In this review, we summarized the adjuvant potential of

Совпадение в полном тексте источника
… Antiproliferative and proapoptotic effects of topotecan in combination with thymoquinone on acute myelogenous leukemia. Clin. Lymphoma Myeloma Leuk. 14(Suppl.), S46–S55. 10.1016/j.clml.2014.04.014 Khalife R., Hodroj M. H., Fakhoury R., Rizk S. (2016). … Thymoquinone from Nigella Sativa seeds promotes the antitumor activity of noncytotoxic doses of Topotecan in human colorectal cancer cells in vitro . Planta Med. 82, 312–321. 10.1055/s-0035-1558289 Khan M. A., Tania M., Wei C., Mei Z., Fu S., Cheng J., et al. (2015). …

Recent Advances in Doxorubicin Formulation to Enhance Pharmacokinetics and Tumor Targeting.

Doxorubicin (DOX), a widely used drug in cancer chemotherapy, induces cell death via multiple intracellular interactions, generating reactive oxygen species and DNA-adducted configurations that induce apoptosis, topoisomerase II inhibition, and histone eviction. Despite its wide therapeutic efficacy in solid tumors, DOX often induces drug resistance and cardiotoxicity. It shows limited intestinal absorption because of low paracellular permeability and P-glycoprotein (P-gp)-mediated efflux. We reviewed various parenteral DOX formulations, such as liposomes, polymeric micelles, polymeric nanopar

Совпадение в полном тексте источника
… Topotecan also showed a marked BA enhancement. With the coadministration of elacridar, the oral BA of topotecan increased from 42% to 97% in cancer patients. In other studies, interindividual variability decreased from 17% to 11% [ 138 , 139 , 140 ]. … Boosting bioavailability of topotecan: What do we gain? J. Clin. Oncol. 2002 20 2918 2919 10.1200/JCO.2002.20.13.2918 12089219 39. Kerklaan B.M. Jager A. Aftimos P. Dieras V. Altintas S. Anders C. Arnedos M. Gelderblom H. Soetekouw P. Gladdines W. …

Antibody drug conjugates in recurrent or metastatic cervical cancer: a focus on tisotumab vedotin state of art.

Cervical cancer (CC) is still characterized by a poor prognosis despite the progress made in its treatment in recent years. Although immunotherapy has improved outcomes for advanced/recurrent disease, there is a significant gap in addressing patients' needs when they progress after platinum and immunotherapy treatments. In this setting, traditional chemotherapy showed limited effectiveness. In this context, antibody-drug conjugates (ADCs) emerged as a promising tool within targeted cancer therapies. Tisotumab vedotin (TV), an ADC targeting tissue factor, represents the first ADC approved by th

Совпадение в полном тексте источника
… Indeed, CC represents the fourth most common cancer in women globally. 1 Until 2014, therapeutic options for metastatic/recurrent CC were significantly limited, primarily relying on platinum-based combinations with paclitaxel, topotecan, gemcitabine, or vinorelbine. … AEs, with sensorimotor neuropathy (2%) being most common. 35 Phase III InnovaTV301/ENGOT cx-12/GOG-3057 ( NCT04697628 ) is a phase III open label trial enrolling patients with pretreated (second or third line) metastatic/recurrent CC randomized to TV 2.0 mg/kg 1q3w or investigators’ choice CT among topotecan …

A comprehensive tool for tumor precision medicine with pharmaco-omics data analysis.

Background: Cancer precision medicine is an effective strategy to fight cancers by bridging genomics and drug discovery to provide specific treatment for patients with different genetic characteristics. Although some public databases and modelling frameworks have been developed through studies on drug response, most of them only considered the ramifications of the drug on the cell line and the effects on the patient still require a huge amount of work to integrate data from various databases and calculations, especially concerning precision treatment. Furthermore, not only efficacy but also th

Совпадение в полном тексте источника
… In addition, although topotecan is recognised as an effective treatment for lung cancer, it shows a high adverse effect score in our database (in detail, it has reversed effects on 1,165 genes and adverse effects on 217 genes and ranks 18,415/20,931 with 0.4 RADB score), which is in line with the existing … Footnotes https://www.ema.europa.eu/en/news/european-medicines-agency-recommends-restricting-use-thiocolchicoside-mouth-injection https://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/cancer-drugs/drugs/topotecan Data availability statement The original contributions presented …