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Smart Targeting To Improve Cancer Therapeutics.

Cancer is the second largest cause of death worldwide with the number of new cancer cases predicted to grow significantly in the next decades. Biotechnology and medicine can and should work hand-in-hand to improve cancer diagnosis and treatment efficacy. However, success has been frequently limited, in particular when treating late-stage solid tumors. There still is the need to develop smart and synergistic therapeutic approaches to achieve the synthesis of strong and effective drugs and delivery systems. Much interest has been paid to the development of smart drug delivery systems (drug-loade

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… Doxorubicin HCl/Pegylated Liposome | Johnson & Johnson | Ovarian cancer, Kaposi sarcoma, multiple myeloma | 1995 Gliadel | Carmustine/Polymeric Wafer | Guilford Pharmaceuticals | Brain tumors | 1996 DaunoXome | Daunorubicin Citrate/Liposome | Galen Pharmaceuticals | Kaposi sarcoma | 1996 DepoCyt | Cytarabine …

Passive Monoclonal and Polyclonal Antibody Therapies

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The evolving global landscape of first-in-class oncology drug innovation.

First-in-class (FIC) oncology drugs-defined by their novel mechanisms of action or targeting of previously unaddressed molecular targets-have emerged as a leading force in cancer therapeutic innovation. In this Review, we delineate the global landscape of FIC oncology drug approvals between 2009 and 2024 and analyze the evolving characteristics of both approved FIC therapies and potential FIC (PFIC) candidates in clinical development. To clarify the underlying dynamics of this evolution, we construct an analytic framework encompassing four distinct archetypes of FIC development: new targets, n

Hijacking the helpers: platelet and neutrophil trafficking in AML and therapeutic exploitation.

Acute myeloid leukemia (AML) remains one of the most aggressive and treatment-resistant hematologic malignancies, driven by clonal expansion of immature myeloid blasts in the bone marrow and peripheral blood. Current therapies-chemotherapy and targeted agents-are limited by poor marrow penetration, systemic toxicity, and rapid development of resistant clones, leaving long-term survival rates low. Clinicians face the persistent challenge of delivering effective therapy while minimizing harm. Platelets and neutrophils-beyond their classical roles in hemostasis and innate immunity-actively suppor

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… Conventional and emerging therapeutic approaches Conventional cytotoxic regimens—most notably anthracycline plus cytarabine induction and consolidation with consideration of allogeneic hematopoietic stem-cell transplantation—remain the foundational curative backbone for fit patients, while molecularly … Conventional cytotoxic induction—most famously the cytarabine + anthracycline “7 + 3” backbone—produced the first durable remissions and established a reproducible pathway to cure for a subset of patients. …

Natural Products as Anticancer Agents: Current Status and Future Perspectives.

Natural products have been an invaluable and useful source of anticancer agents over the years. Several compounds have been synthesized from natural products by modifying their structures or by using naturally occurring compounds as building blocks in the synthesis of these compounds for various purposes in different fields, such as biology, medicine, and engineering. Multiple modern and costly treatments have been applied to combat cancer and limit its lethality, but the results are not significantly refreshing. Natural products, which are a significant source of new therapeutic drugs, are cu

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… Recently, Saikia et al. reported that combined use of heteronemin with cytarabine increases its sensitivity against leukemia (HL-60) cells by downregulating downstream targets of Ras signaling pathway such as AP-1, NF-kβ, AMPK, and c-myc; as a result it produces synergistic effects, inhibits the growth …

Viruses

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HIF-1α signaling: Essential roles in tumorigenesis and implications in targeted therapies.

The hypoxic microenvironment is an essential characteristic of most malignant tumors. Notably, hypoxia-inducible factor-1 alpha (HIF-1α) is a key regulatory factor of cellular adaptation to hypoxia, and many critical pathways are correlated with the biological activity of organisms via HIF-1α. In the intra-tumoral hypoxic environment, HIF-1α is highly expressed and contributes to the malignant progression of tumors, which in turn results in a poor prognosis in patients. Recently, it has been indicated that HIF-1α involves in various critical processes of life events and tumor development via r

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… Furthermore, they observed that echinomycin monotherapy proved to be more effective in killing AML cells than conventional combination chemotherapy (cytarabine plus daunorubicin) via the establishment of a mouse model of TP53 -mutated AML. 102 In addition, a clinical study demonstrated that HIF-1α is …

Agents contributing to secondary immunodeficiency development in patients with multiple myeloma, chronic lymphocytic leukemia and non-Hodgkin lymphoma: A systematic literature review.

IntroductionPatients with hematological malignancies (HMs), like chronic lymphocytic leukemia (CLL), multiple myeloma (MM), and non-Hodgkin lymphoma (NHL), have a high risk of secondary immunodeficiency (SID), SID-related infections, and mortality. Here, we report the results of a systematic literature review on the potential association of various cancer regimens with infection rates, neutropenia, lymphocytopenia, or hypogammaglobulinemia, indicative of SID.MethodsA systematic literature search was performed in 03/2022 using PubMed to search for clinical trials that mentioned in the title and

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… Classes of drugs | Agents Alkylating agents | Bendamustine, chlorambucil, cisplatin, cyclophosphamide, ifosfamide, and melphalan Antimetabolites | Cladribine, cytarabine, fludarabine, methotrexate, nelarabine, pentostatin, and pralatrexate Anti-tumor antibiotics | Doxorubicin and pixantrone BH3 mimetic …

The prevention of disease relapse after allogeneic hematopoietic cell transplantation in acute myeloid leukemia.

Disease relapse represents by far the most frequent cause of hematopoietic cell transplantation (HCT) failure. Patients with acute leukemia suffering relapse after HCT have limited conventional treatment options with little possibility of cure and represent, de facto, suitable candidates for the evaluation of novel cellular and biological-based therapies. Donor lymphocyte infusions (DLI) has been one of the first cellular therapies adopted to treat post HCT relapse of acute leukemia patients and still now, it is widely adopted in preemptive and prophylactic settings, with renewed interest for

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… clinical outcomes of FLAMSA-RIC platform and to reduce the total body irradiation (TBI) and amsacrine-associated toxic rates, The French published the results of a multicenter prospective phase 2 study, evaluating the efficacy of an alternative sequential regimen of clofarabine-based chemotherapy, with cytarabine …

Current Status and Perspectives of Allogeneic Hematopoietic Stem Cell Transplantation in Elderly Patients with Acute Myeloid Leukemia.

As in younger patients, allogeneic stem cell transplantation (alloHSCT) offers the best chance for durable remission in older patients (≥60 years) with acute myeloid leukemia (AML). However, defining the best treatment strategy (and in particular, whether or not to proceed to alloHSCT) for elderly patients with AML remains a difficult decision for the hematologist, since potential toxicity of conditioning regimens, risks of graft-versus-host disease, impaired immune reconstitution and the need for prolonged immunosuppression may be of major concern in these vulnerable patients with complex nee

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… Kantarjian HM , Thomas XG , Dmoszynska A , et al Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. …

Histone Deacetylases (HDACs) Guided Novel Therapies for T-cell lymphomas.

T-cell lymphomas are a heterogeneous group of cancers with different pathogenesis and poor prognosis. Histone deacetylases (HDACs) are epigenetic modifiers that modulate many key biological processes. In recent years, HDACs have been fully investigated for their roles and potential as drug targets in T-cell lymphomas. In this review, we have deciphered the modes of action of HDACs, HDAC inhibitors as single agents, and HDACs guided combination therapies in T-cell lymphomas. The overview of HDACs on the stage of T-cell lymphomas, and HDACs guided therapies both as single agents and combination

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… The combination of Romidepsin with conventional anti-leukemic agents (Methotrexate, Vincristine, Imatinib, Cytarabine, Carboplatin, Doxorubicin, 4-hydroperoxy-cyclophosphamide, Etoposide, 6-mercaptopurine and SN-38) has exihibited additive effects in T/B-cell lymphomas, making Romidepsin a promising …

Тематический анализ прогноза, диагностики и терапии циркулирующих биомаркеров миРНА в борцезомибно-стойких миеломах.

ЦЕЛЬ: Растущий спрос на точную медицину стимулировал молекулярные диагностические исследования, с тем чтобы подчеркнуть полезность микроРНК в качестве важных биомаркеров. В недавних исследованиях подчеркивается роль МИРНА как перспективных, диагностических и терапевтических биомаркеров в управлении и мониторинге нескольких пациентов, страдающих миеломой. Цель этого обзора заключается в том, чтобы представить последние сведения о потенциале распространения миРНА в качестве прогнозирующих, диагностических и терапевтических биомаркеров в нескольких миеломах, устойчивых к бортезомибу. МЕТОДЫ: С эт

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… Overexpression of MRP4 (ABCC4) and MRP5 (ABCC5) confer resistance to the nucleoside analogs cytarabine and troxacitabine, but not gemcitabine. SpringerPlus 2014; 3(1): 732. 47. Kozalak G, Öksüzoğlu E. …

Recent Insights into the Creation of Histone Deacetylase Inhibitors for the Treatment of Human Diseases.

This review examines publications over the past two years devoted to histone deacetylase inhibitors for the treatment of cancer, diseases of the nervous, cardiovascular, digestive, and respiratory systems, and autoimmune diseases. The review covers various classes of histone deacetylase inhibitors depending on the zinc-binding group, in particular hydroxamic acids, benzamides, hydrazides, carboxylic acids, and cyclic peptides. The review pays special attention to the mechanisms of development of pathologies involving various isoforms of histone deacetylases. The review shows that, for the trea

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… More powerful antitumor effect in vivo in combination with cytarabine compared to monotherapy. | [ 77 ] | Leukemia | 1. Inhibition of proliferation of human leukemia monocytic Tohoku Hospital Pediatrics-1 (THP-1) cell line (IC 50 1.6–2.2 μM at 48 h). 2. …

Therapeutic Potential of Chlorogenic Acid in Chemoresistance and Chemoprotection in Cancer Treatment.

Chemotherapeutic drugs are indispensable in cancer treatment, but their effectiveness is often lessened because of non-selective toxicity to healthy tissues, which triggers inflammatory pathways that are harmful to vital organs. In addition, tumors' resistance to drugs causes failures in treatment. Chlorogenic acid (5-caffeoylquinic acid, CGA), found in plants and vegetables, is promising in anticancer mechanisms. In vitro and animal studies have indicated that CGA can overcome resistance to conventional chemotherapeutics and alleviate chemotherapy-induced toxicity by scavenging free radicals

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… Pyrimidine analogs, such as cytarabine (Ara-C) and 5-FU, constitute an important pharmacological group in antineoplastic treatment, with broad-spectrum activity [ 111 ]. 5-FU is a fluorinated pyrimidine analog of uracil that acts by competitive inhibition of thymidylate synthase. …

Different Strategies to Overcome Resistance to Proteasome Inhibitors-A Summary 20 Years after Their Introduction.

Proteasome inhibitors (PIs), bortezomib, carfilzomib, and ixazomib, are the first-line treatment for multiple myeloma (MM). They inhibit cytosolic protein degradation in cells, which leads to the accumulation of misfolded and malfunctioned proteins in the cytosol and endoplasmic reticulum, resulting in cell death. Despite being a breakthrough in MM therapy, malignant cells develop resistance to PIs via different mechanisms. Understanding these mechanisms drives research toward new anticancer agents to overcome PI resistance. In this review, we summarize the mechanism of action of PIs and how M

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… Disulfiram overcomes bortezomib and cytarabine resistance in Down-syndrome-associated acute myeloid leukemia cells J. Exp. Clin. Cancer Res. 2017 36 22 10.1186/s13046-017-0493-5 28143565 PMC5286849 99. Xu Y. Zhou Q. Feng X. Dai Y. Jiang Y. Jiang W. Liu X. Xing X. Wang Y. Ni Y. …

Marine Natural Products with Activities against Prostate Cancer: Recent Discoveries.

Prostate cancer is the most common cancer in men, with over 52,000 new cases diagnosed every year. Diagnostics and early treatment are potentially hindered by variations in screening protocols, still largely reliant on serum levels of acid phosphatase and prostate-specific antigen, with tumour diagnosis and grading relying on histopathological examination. Current treatment interventions vary in terms of efficacy, cost and severity of side effects, and relapse can be aggressive and resistant to the current standard of care. For these reasons, the scientific community is looking for new chemoth

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… National Center for Biotechnology Information PubChem Compound Summary for CID 6253, Cytarabine. [(accessed on 30 December 2022)];2022 Available online: https://pubchem.ncbi.nlm.nih.gov/compound/6253#section=2D-Structure . 32. …

Immune checkpoints represent a promising breakthrough in targeted therapy and prognosis of myelodysplastic syndrome.

Myelodysplastic syndrome (MDS) is a hematological malignancy of undetermined etiology, possibly linked to chromosomal structural alterations, genetic mutations, presentation and carcinogenicity of variant antigens on cell surface, and the generation of pro-inflammatory microenvironment in the bone marrow. Current drugs are unable to cure this disease, and therefore, decreasing the survival and proliferation of malignant cells to delay disease progression and extend the survival time of patients becomes the primary approach to management. In recent years, the immune system has received increasi

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… Another study indicated that NFE2 could mediate the Ara-C (cytarabine) resistance in high-risk MDS patients by directly targeting DUSP1, and NFE2 knock-out could lead to re-sensitization [ 36 ]. These findings suggest that NFE2 is also the basis of development of drug resistance in MDS cells. …

Complete spectrum of adverse events associated with chimeric antigen receptor (CAR)-T cell therapies.

Chimeric antigen receptor (CAR)-T cell therapies have been approved by FDA to treat relapsed or refractory hematological malignancies. However, the adverse effects of CAR-T cell therapies are complex and can be challenging to diagnose and treat. In this review, we summarize the major adverse events, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and CAR T-cell associated HLH (carHLH), and discuss their pathophysiology, symptoms, grading, and diagnosis systems, as well as management. In a future outlook, we also provide an overview of

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… According to the study by Neelapu et al . , if no improvement is seen within 48 h, etoposide for refractory HLH should be considered, and intrathecal cytarabine may be used for HLH-associated neurotoxicity [ 34 ]. …

COVID-19 in Adult Patients with Hematological Malignancies-Lessons Learned after Three Years of Pandemic.

The COVID-19 pandemic is undoubtedly the most difficult health challenge of the 21st century with more than 600 million laboratory-confirmed SARS-CoV-2 infections and over 6.5 million deaths worldwide. The coronavirus pandemic contributed to rapid development of mRNA vaccines, which, along with new antiviral drugs, have been the subject of extensive research for many decades. Nevertheless, elderly, multi-morbid and immunocompromised patients continue to face a more severe clinical course and a higher risk of death from COVID-19, even now that the risk of COVID-19 in the general population is s

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… Viral Clearance with Neutrophil Recovery in a Patient with Active COVID-19 Infection and Refractory Acute Myeloid Leukemia Who Underwent Successful Reinduction with Cytarabine/Idarubicin Case Rep. Oncol. 2022 15 705 712 10.1159/000525766 36157697 PMC9459561 99. Keam S.J. …

Patient-Derived Organoids Can Guide Personalized-Therapies for Patients with Advanced Breast Cancer.

Most breast cancers at an advanced stage exhibit an aggressive nature, and there is a lack of effective anticancer options. Herein, the development of patient-derived organoids (PDOs) is described as a real-time platform to explore the feasibility of tailored treatment for refractory breast cancers. PDOs are successfully generated from breast cancer tissues, including heavily treated specimens. The microtubule-targeting drug-sensitive response signatures of PDOs predict improved distant relapse-free survival for invasive breast cancers treated with adjuvant chemotherapy. It is further demonstr

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… Notably, PDOs exhibited simultaneous sensitivity or resistance to nucleic acid synthesis inhibitors (gemcitabine, cladribine, and cytarabine) and microtubule inhibitors (docetaxel, paclitaxel, vinorelbine, ixabepilone, vincristine, and vinblastine). …