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Computational Drug Repurposing Across the Multiple Myeloma Spectrum: From MGUS to MM.

Background/objectivesMultiple myeloma (MM) is a challenging, B cell malignancy characterised by the uncontrolled proliferation of plasma cells within the bone marrow. Despite significant advances in treatment options nowadays, MM remains an incurable malignancy, with the majority of patients succumbing to the disease. MM develops from a pre-malignant state known as monoclonal gammopathy of unknown significance (MGUS), which then has the potential to evolve either into smouldering (asymptomatic) multiple myeloma (SMM) or into MM. Since novel drug discovery takes years to reach the clinic, drug

Chemotherapy Side-Effects: Not All DNA Damage Is Equal.

Recent advances have increased survival rates of children and adults suffering from cancer thanks to effective anti-cancer therapy, such as chemotherapy. However, during treatment and later in life they are frequently confronted with the severe negative side-effects of their life-saving treatment. The occurrence of numerous features of accelerated aging, seriously affecting quality of life, has now become one of the most pressing problems associated with (pediatric) cancer treatment. Chemotherapies frequently target and damage the DNA, causing mutations or genome instability, a major hallmark

Chromosome 1q21 abnormalities in multiple myeloma.

Gain of chromosome 1q (+1q) is one of the most common recurrent cytogenetic abnormalities in multiple myeloma (MM), occurring in approximately 40% of newly diagnosed cases. Although it is often considered a poor prognostic marker in MM, +1q has not been uniformly adopted as a high-risk cytogenetic abnormality in guidelines. Controversy exists regarding the importance of copy number, as well as whether +1q is itself a driver of poor outcomes or merely a common passenger genetic abnormality in biologically unstable disease. Although the identification of a clear pathogenic mechanism from +1q rem

Cytokine receptor IL27RA is an NF-κB-responsive gene involved in CD38 upregulation in multiple myeloma.

Multiple myeloma (MM) shows constitutive activation of canonical and noncanonical nuclear factor κB (NF-κB) signaling via genetic mutations or tumor microenvironment (TME) stimulations. A subset of MM cell lines showed dependency for cell growth and survival on the canonical NF-κB transcription factor RELA alone, suggesting a critical role for a RELA-mediated biological program in MM pathogenesis. Here, we determined the RELA-dependent transcriptional program in MM cell lines and found the expression of the cell surface molecules interleukin-27 receptor-α (IL-27Rα) and the adhesion molecule JA

Advances in the assessment of minimal residual disease in mantle cell lymphoma.

The clinical impact of minimal residual disease detection at early time points or during follow-ups has been shown to accurately predict relapses among patients with lymphomas, mainly in follicular and diffuse large B cell lymphoma. The field of minimal residual disease testing in mantle cell lymphoma is still evolving but has great impact in determining the prognosis. Flow cytometry and polymerase chain reaction-based testing are most commonly used methods in practice; however, these methods are not sensitive enough to detect the dynamic changes that underline lymphoma progression. Newer meth

Abstracts of the 28th Annual San Antonio Breast Cancer Symposium, December 8-11, 2005, San Antonio, Texas, USA.

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Concept of natural genome reconstruction.Part 5. Analysis of changes in the lifespan of old animals after reinfusion of bone marrow cells derived from old animals and treated with hDNAgr in combination with recombinant human angiogenin.

Two series of tests were performed, on mice and rats, to assess the lifespan of old animals reinfused with bone marrow cells from old animals treated with fragmented human DNA (hDNAgr), recombinant human angiogenin, and both preparations together. Animals reinfused with untreated bone marrow cells from old animals or bone marrow cells from young animals were used as comparison groups. Using both outbred mice and CBA/Lac mice, no significant increase in the lifespan of animals reinfused with bone marrow cells treated with the hDNAgr was found compared with the group of mice reinfused with untre

Recent Developments and Evolving Therapeutic Strategies in KMT2A-Rearranged Acute Leukemia.

BackgroundRearrangements of the histone-lysine-N-methyltransferase (KMT2A), previously referred to as mixed-lineage leukemia (MLL), are among the most common chromosomal abnormalities in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), involving numerous different fusion partners. KMT2A-rearranged (KMT2A-r) leukemia is characterized by a rapid onset, aggressive progression, and significantly worse prognosis compared to non-KMT2A-r leukemias. Even with contemporary chemotherapeutic treatments and hematopoietic stem cell transplantations (HSCT), patients with KM

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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… As a tumor suppressor, WT1 regulates transcriptional pathways such as the activation of p21, which inhibits Cyclin D and controls cell cycle progression. WT1 also promotes apoptosis through the activation of the pro-apoptotic protein BAX. … As a tumor suppressor, WT1 regulates transcriptional pathways such as the activation of p21, which inhibits Cyclin D and controls cell cycle progression. WT1 also promotes apoptosis through the activation of the pro-apoptotic protein BAX. …

Библиометрический и биоинформатический анализ перерождения в многократной миеломе: тенденции и горячих точек исследований и связанные с ними генетические пути (Associated Geneal Pathways)2000-2023).

ЦЕЛЬ: Цель настоящего исследования заключается в проведении библиометрического визуального анализа и биоинформатического анализа для изучения исследовательских горячих точек и тенденций развития почечных расстройств в множестве миелом, включая соответствующие гены и каналы сигнала в прошлом. two десятилетиями. МЕТОДЫ: База данных " Web of Science Core Collection " использовалась в качестве источника данных для извлечения литературы о дефектах почек в множестве миеломы. 2000 в адрес 2023. Выбранная литература была проанализирована с использованием библиометрического и биоинформатическ

Treatment of multiple myeloma with selinexor: a review.

Over the last 20 years, breakthroughs in accessible therapies for the treatment of multiple myeloma (MM) have been made. Nevertheless, patients with MM resistant to immunomodulatory drugs, proteasome inhibitors, and anti-CD38 monoclonal antibodies have a very poor outcome. Therefore, it is necessary to explore new drugs for the treatment of MM. This review summarizes the mechanism of action of selinexor, relevant primary clinical trials, and recent developments in both patients with relapsed/refractory myeloma and patients with newly diagnosed myeloma. Selinexor may be useful for the treatment

Bioactivities and Mechanisms of Action of Sinomenine and Its Derivatives: A Comprehensive Review.

Sinomenine, an isoquinoline alkaloid extracted from the roots and stems of Sinomenium acutum, has been extensively studied for its derivatives as bioactive agents. This review concentrates on the research advancements in the biological activities and action mechanisms of sinomenine-related compounds until November 2023. The findings indicate a broad spectrum of pharmacological effects, including antitumor, anti-inflammation, neuroprotection, and immunosuppressive properties. These compounds are notably effective against breast, lung, liver, and prostate cancers, exhibiting IC50 values of appro

Indication Expansion Dynamics and Trial Characteristics of Novel Multi-Indication Anti-Cancer Drugs in China (2000-2024): A Cross-Sectional Study.

PurposeTo perform a cross-sectional analysis of the indication expansion trends and pivotal trial features of novel multi-indication anti-cancer drugs approved in China from 2000 to 2024.MethodsWe conducted a cross‑sectional review of 74 novel multi-indication anti-cancer drugs approved by the National Medical Products Administration (NMPA) in China from 2000 to 2024, encompassing 265 total indications. Data were collected from multiple sources, including the NMPA, the Center for Drug Evaluation (CDE) of the NMPA, the National Healthcare Security Administration (NHSA), ClinicalTrials.gov, and

Radiotherapy plus CAR-T cell therapy to date: A note for cautions optimism?

Radiotherapy (RT) is a traditional therapeutic regime that focuses on ionizing radiation, however, RT maintains largely palliative due to radioresistance. Factors such as hypoxia, the radiosensitivity of immune cells, and cancer stem cells (CSCs) all come into play in influencing the significant impact of radioresistance in the irradiated tumor microenvironment (TME). Due to the substantial advances in the treatment of malignant tumors, a promising approach is the genetically modified T cells with chimeric antigen receptors (CARs) to eliminate solid tumors. Moreover, CAR-T cells targeting CSC-

Annexin A1 affects tumor metastasis through epithelial-mesenchymal transition: a narrative review.

Background and objectiveAnnexin A1 (annexin I, ANXA1), the first discovered member of the annexin superfamily, plays important roles in tumor development, invasion, metastasis, apoptosis and drug resistance based on tumor type-specific patterns of expression. The acquisition of the epithelial-mesenchymal transition (EMT) characteristics is an essential mechanism of metastasis because they increase the mobility and invasiveness of cancer cells. Cancer invasion and metastasis remain major health problems worldwide. Elucidating the role and mechanism of ANXA1 in the occurrence of EMT will help ad

MicroRNAs and long non-coding RNAs in pancreatic cancer: From epigenetics to potential clinical applications.

MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two relevant classes of non-coding RNAs (ncRNAs) that play a pivotal role in a number of molecular processes through different epigenetic regulatory mechanisms of gene expression. As a matter of fact, the altered expression of these types of RNAs leads to the development and progression of a varied range of multifactorial human diseases. Several recent reports elucidated that miRNA and lncRNAs have been implicated in pancreatic cancer (PC). For instance, dysregulation of such ncRNAs has been found to be associated with chemoresistance,

MicroRNAs in Pancreatic Cancer: biomarkers, prognostic, and therapeutic modulators.

A severe lack of early diagnosis coupled with resistance to most available therapeutic options renders pancreatic cancer as a major clinical concern. The limited efficacy of current treatments necessitates the development of novel therapeutic strategies that are based on an understanding of the molecular mechanisms involved in pancreatic cancer progression. MicroRNAs (miRNAs) are non-coding small RNAs that regulate the expression of multiple proteins in the post-translation process and thus have promise as biomarkers, prognostic agents, and as advanced pancreatic therapies. Profiling of deregu

Hyaluronic Acid as a Modern Approach in Anticancer Therapy-Review.

Hyaluronic acid (HA) is a linear polysaccharide and crucial component of the extracellular matrix (ECM), maintaining tissue hydration and tension. Moreover, HA contributes to embryonic development, healing, inflammation, and cancerogenesis. This review summarizes new research on the metabolism and interactions of HA with its binding proteins, known as hyaladherins (CD44, RHAMM), revealing the molecular basis for its distinct biological function in the development of cancer. The presence of HA on the surface of tumor cells is a sign of an adverse prognosis. The involvement of HA in malignancy h

Revisiting Proteasome Inhibitors: Molecular Underpinnings of Their Development, Mechanisms of Resistance and Strategies to Overcome Anti-Cancer Drug Resistance.

Proteasome inhibitors have shown relevant clinical activity in several hematological malignancies, namely in multiple myeloma and mantle cell lymphoma, improving patient outcomes such as survival and quality of life, when compared with other therapies. However, initial response to the therapy is a challenge as most patients show an innate resistance to proteasome inhibitors, and those that respond to the therapy usually develop late relapses suggesting the development of acquired resistance. The mechanisms of resistance to proteasome inhibition are still controversial and scarce in the literat

New approaches for cancer treatment: antitumor drugs based on gene-targeted nucleic acids.

Currently, the main way to fight cancer is still chemotherapy. This method of treatment is at the height of its capacity, so, setting aside the need for further improvements in traditional treatments for neoplasia, it is vital to develop now approaches toward treating malignant tumors. This paper reviews innovational experimental approaches to treating malignant malformations based on the use of gene-targeted drugs, such as antisense oligonucleotides (asON), small interfering RNA (siRNA), ribozymes, and DNAzymes, which can all inhibit oncogene expression. The target genes for these drugs are t