Результаты поиска

Targeting hedgehog signaling in myelofibrosis and other hematologic malignancies.

Treatment of myelofibrosis (MF), a BCR-ABL-negative myeloproliferative neoplasm, is challenging. The only current potentially curative option, allogeneic hematopoietic stem cell transplant, is recommended for few patients. The remaining patients are treated with palliative therapies to manage MF-related anemia and splenomegaly. Identification of a mutation in the Janus kinase 2 (JAK2) gene (JAK2 V617F) in more than half of all patients with MF has prompted the discovery and clinical development of inhibitors that target JAK2. Although treatment with JAK2 inhibitors has been shown to improve sy

Advancing Medulloblastoma Treatment: Molecular Mechanisms, Drug Repurposing, and Precision Therapies.

Medulloblastomas are the most common malignant pediatric brain tumors, representing approximately 20% of the central nervous system cancers in children. These tumors are highly heterogeneous and classified into four molecular subgroups-WNT, SHH, Group 3, and Group 4-each with distinct genetic and epigenetic profiles that influence tumor behavior, therapeutic response, and patient outcomes. Advances in molecular diagnostics have improved the subclassification of medulloblastomas, yet treatment outcomes for high-risk subtypes, particularly Group 3, remain poor, with current modalities often asso

Совпадение в полном тексте источника
… BCOR BCL6 corepressor, CTNNB1 catenin beta 1, i17q isochromosome 17q, KDM6A lysine demethylase 6A, MYC myelocytomatosis, MYCN myelocytomatosis neuroblastoma, PRDM6 PR/SET domain 6, SHH Sonic hedgehog pathway, SMO smoothened receptor, TP53 tumor protein 53, WNT wingless/integrated pathway Fig. 1 Genetic … BCOR BCL6 corepressor, CTNNB1 catenin beta 1, i17q isochromosome 17q, KDM6A lysine demethylase 6A, MYC myelocytomatosis, MYCN myelocytomatosis neuroblastoma, PRDM6 PR/SET domain 6, SHH Sonic hedgehog pathway, SMO smoothened receptor, TP53 tumor protein 53, WNT wingless/integrated pathway Oncogenic Signaling …

Profile of Glasdegib for the Treatment of Newly Diagnosed Acute Myeloid Leukemia (AML): Evidence to Date.

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy primarily affecting older adults. Historically, the highest rates of response have been achieved with intensive induction chemotherapy; however, a significant portion of older or unfit adults with AML are unable to tolerate intensive therapy or have chemotherapy-resistant disease, creating a large need for active and less intensive treatment strategies. Glasdegib, an oral inhibitor of the transmembrane protein Smoothened (SMO) involved in the Hedgehog (Hh) signaling pathway, was approved in 2018 for older or unfit adults with

Not so Fast: Co-Requirements for Sonic Hedgehog Induced Brain Tumorigenesis.

The Sonic hedgehog (Shh) pathway plays an integral role in cellular proliferation during normal brain development and also drives growth in a variety of cancers including brain cancer. Clinical trials of Shh pathway inhibitors for brain tumors have yielded disappointing results, indicating a more nuanced role for Shh signaling. We postulate that Shh signaling does not work alone but requires co-activation of other signaling pathways for tumorigenesis and stem cell maintenance. This review will focus on the interplay between the Shh pathway and these pathways to promote tumor growth in brain tu

From Bench to Bedside and Beyond: Therapeutic Scenario in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a heterogeneous group of clonal disorders characterized by abnormal proliferation of undifferentiated myeloid progenitors, impaired hematopoiesis, and variable response to therapy. To date, only about 30% of adult patients with AML become long-term survivors and relapse and/or disease refractoriness are the major cause of treatment failure. Thus, this is an urgent unmet clinical need and new drugs are envisaged in order to ameliorate disease survival outcomes. Here, we review the latest therapeutic approaches (investigational and approved agents) for AML treatme

Targeting cancer stem cells in drug discovery: Current state and future perspectives.

In recent decades, cancer stem cells (CSCs) have been increasingly identified in many malignancies. CSC-related signaling pathways and their functions provide new strategies for treating cancer. The aberrant activation of related signaling pathways (e.g., Wnt, Notch, and Hedgehog pathways) has been linked to multiple types of malignant tumors, which makes these pathways attractive targets for cancer therapy. CSCs display many characteristic features, such as self-renewal, differentiation, high tumorigenicity, and drug resistance. Therefore, there is an urgent need to develop new therapeutic st

Emerging agents that target signaling pathways to eradicate colorectal cancer stem cells.

Colorectal cancer (CRC) represents the third most commonly diagnosed cancer and the second leading cause of cancer death worldwide. The modern concept of cancer biology indicates that cancer is formed of a small population of cells called cancer stem cells (CSCs), which present both pluripotency and self-renewal properties. These cells are considered responsible for the progression of the disease, recurrence and tumor resistance. Interestingly, some cell signaling pathways participate in CRC survival, proliferation, and self-renewal properties, and most of them are dysregulated in CSCs, includ

Heterogeneous Contributing Factors in MPM Disease Development and Progression: Biological Advances and Clinical Implications.

Malignant pleural mesothelioma (MPM) tumors are remarkably aggressive and most patients only survive for 5-12 months; irrespective of stage; after primary symptoms appear. Compounding matters is that MPM remains unresponsive to conventional standards of care; including radiation and chemotherapy. Currently; instead of relying on molecular signatures and histological typing; MPM treatment options are guided by clinical stage and patient characteristics because the mechanism of carcinogenesis has not been fully elucidated; although about 80% of cases can be linked to asbestos exposure. Several m

One step further in targeting acute leukemia by combining antibody-based immunotherapies and small molecule inhibitors.

BackgroundAcute leukemia is a bone marrow-related disease characterized by fast progression and the production of immature blood cells rather than normal ones that are classified as either acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). Chemotherapy as a conventional treatment has many side effects, thus new medications that target intracellular molecules and cell surface markers on leukemic cells have been developed in the last decades.Main bodyThis review focuses on antibody-based targeted treatments, which so far, have been shown to improve the treatment outcomes, includ

FDA-Approved Small Molecule Compounds as Drugs for Solid Cancers from Early 2011 to the End of 2021.

Solid cancers are the most common types of cancers diagnosed globally and comprise a large number of deaths each year. The main challenge currently in drug development for tumors raised from solid organs is to find more selective compounds, which exploit specific molecular targets. In this work, the small molecule drugs registered by the Food and Drug Administration (FDA) for solid cancers treatment between 2011 and 2022 were identified and analyzed by investigating a type of therapy they are used for, as well as their structures and mechanisms of action. On average, 4 new small molecule agent

Совпадение в полном тексте источника
… SMO : smoothened receptor. SUFU : suppressor of fused protein. GLI : glioma-associated oncogene protein. GLIr : repressor form of GLI. Created with BioRender.com based on information in Refs. [ 203 , 204 ]. …

Molecular interactions of miR-338 during tumor progression and metastasis.

BackgroundCancer, as one of the main causes of human deaths, is currently a significant global health challenge. Since the majority of cancer-related deaths are associated with late diagnosis, it is necessary to develop minimally invasive early detection markers to manage and reduce mortality rates. MicroRNAs (miRNAs), as highly conserved non-coding RNAs, target the specific mRNAs which are involved in regulation of various fundamental cellular processes such as cell proliferation, death, and signaling pathways. MiRNAs can also be regulated by long non-coding RNAs (lncRNAs) and circular RNAs (

Dual targeting with 224Ra/212Pb-conjugates for targeted alpha therapy of disseminated cancers: A conceptual approach.

Metastases are the primary cause of death among cancer patients and efficacious new treatments are sorely needed. Targeted alpha-emitting radiopharmaceuticals that are highly cytotoxic may fulfill this critical need. The focus of this paper is to describe and explore a novel technology that may improve the therapeutic effect of targeted alpha therapy by combining two radionuclides from the same decay chain in the same solution. We hypothesize that the dual targeting solution containing bone-seeking 224Ra and cell-directed complexes of progeny 212Pb is a promising approach to treat metastatic c

Novel agents for advanced pancreatic cancer.

Pancreatic cancer is relatively insensitive to conventional chemotherapy. Therefore, novel agents targeting dysregulated pathways (MAPK/ERK, EGFR, TGF-β, HEDGEHOG, NOTCH, IGF, PARP, PI3K/AKT, RAS, and Src) are being explored in clinical trials as monotherapy or in combination with cytotoxic chemotherapy. This review summarizes the most recent advances with the targeted therapies in the treatment of patients with advanced pancreatic cancer.

Keyword Index for Volume 103

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

Organoids as Innovative Models for Bone and Joint Diseases.

Bone is one of the key components of the musculoskeletal system. Bone and joint disease are the fourth most widespread disease, in addition to cardiovascular disease, cancer, and diabetes, which seriously affect people's quality of life. Bone organoids seem to be a great model by which to promote the research method, which further could improve the treatment of bone and joint disease in the future. Here, we introduce the various bone and joint diseases and their biology, and the conditions of organoid culture, comparing the in vitro models among 2D, 3D, and organoids. We summarize the differin

Absence of Biomarker-Driven Treatment Options in Small Cell Lung Cancer, and Selected Preclinical Candidates for Next Generation Combination Therapies.

Lung cancer is the second most common cancer in the United States, and small cell lung cancer (SCLC) accounts for about 15% of all lung cancers. In SCLC, more than other malignancies, the standard of care is based on clinical demonstration of efficacy, and less on a mechanistic understanding of why certain treatments work better than others. This is in large part due to the virulence of the disease, and lack of clinically or biologically relevant biomarkers beyond routine histopathology. While first line therapies work in the majority of patients with extensive stage disease, development of re

Molecular Approaches To Target GPCRs in Cancer Therapy

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

Anti-Cancer Stem-like Cell Compounds in Clinical Development - An Overview and Critical Appraisal.

Cancer stem-like cells (CSC) represent a subpopulation of tumor cells with elevated tumor-initiating potential. Upon differentiation, they replenish the bulk of the tumor cell population. Enhanced tumor-forming capacity, resistance to antitumor drugs, and metastasis-forming potential are the hallmark traits of CSCs. Given these properties, it is not surprising that CSCs have become a therapeutic target of prime interest in drug discovery. In fact, over the last few years, an enormous number of articles describing compounds endowed with anti-CSC activities have been published. In the meanwhile,

Pathogenesis of Oral Toxicities Associated with Targeted Therapy and Immunotherapy.

Targeted therapy and immunotherapy have redefined cancer treatment. While they have enhanced tumor response and improved survival rates in many cancer types, toxicities continue to occur, and these often involve the oral cavity. Broadly reported as "mucositis" or "stomatitis," oral toxicities induced by targeted therapies differ clinically and mechanistically from those associated with conventional chemotherapy. Manifesting primarily as mucosal lesions, salivary gland hypofunction, or orofacial neuropathies, these oral toxicities may nonetheless lead to significant morbidity and impact patient

Molecular targeted therapy for anticancer treatment.

Since the initial clinical approval in the late 1990s and remarkable anticancer effects for certain types of cancer, molecular targeted therapy utilizing small molecule agents or therapeutic monoclonal antibodies acting as signal transduction inhibitors has served as a fundamental backbone in precision medicine for cancer treatment. These approaches are now used clinically as first-line therapy for various types of human cancers. Compared to conventional chemotherapy, targeted therapeutic agents have efficient anticancer effects with fewer side effects. However, the emergence of drug resistanc