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ChemMedChem Sep 2023Supramolecular assemblies made by the self-assembly of peptides are finding an increasing number of applications in various fields. While the early exploration of... (Review)
Review
Supramolecular assemblies made by the self-assembly of peptides are finding an increasing number of applications in various fields. While the early exploration of peptide assemblies centered on tissue engineering or regenerative medicine, the recent development has shown that peptide assemblies can act as supramolecular medicine for cancer therapy. This review covers the progress of applying peptide assemblies for cancer therapy, with the emphasis on the works appeared over the last five years. We start with the introduction of a few seminal works on peptide assemblies, then discuss the combination of peptide assemblies with anticancer drugs. Next, we highlight the use of enzyme-controlled transformation or shapeshifting of peptide assemblies for inhibiting cancer cells and tumors. After that, we provide the outlook for this exciting field that promises new kind of therapeutics for cancer therapy.
Topics: Humans; Peptides; Tissue Engineering; Antineoplastic Agents; Neoplasms
PubMed: 37380607
DOI: 10.1002/cmdc.202300258 -
International Journal of Molecular... Nov 2023Cancer poses a significant global public health challenge [...].
Cancer poses a significant global public health challenge [...].
Topics: Humans; Antineoplastic Agents; Neoplasms
PubMed: 38003270
DOI: 10.3390/ijms242216066 -
Cancer Treatment Reviews Jul 2024The advent of molecular profiling and the generalization of next generation sequencing in oncology has enabled the identification of patients who could benefit from... (Review)
Review
The advent of molecular profiling and the generalization of next generation sequencing in oncology has enabled the identification of patients who could benefit from targeted agents. Since the tumor-agnostic approval of pembrolizumab for patients with MSI-High tumors in 2017, different molecularly-guided therapeutics have been awarded approvals and progressively incorporated in the treatment landscape across multiple tumor types. As the number of tumor-agnostic targets considered druggable expands in the clinic, novel challenges will reshape the drug development field involving all the stakeholders in oncology. In this review, we provide an overview of current tumor-agnostic approvals and discuss promising candidate therapeutics for tumor-agnostic designation and challenges for their broad implementation.
Topics: Humans; Drug Development; Neoplasms; Molecular Targeted Therapy; Antineoplastic Agents; High-Throughput Nucleotide Sequencing; Antibodies, Monoclonal, Humanized
PubMed: 38763053
DOI: 10.1016/j.ctrv.2024.102747 -
Journal of Hematology & Oncology Jul 2023NEDDylation, a post-translational modification through three-step enzymatic cascades, plays crucial roles in the regulation of diverse biological processes.... (Review)
Review
NEDDylation, a post-translational modification through three-step enzymatic cascades, plays crucial roles in the regulation of diverse biological processes. NEDD8-activating enzyme (NAE) as the only activation enzyme in the NEDDylation modification has become an attractive target to develop anticancer drugs. To date, numerous inhibitors or agonists targeting NAE have been developed. Among them, covalent NAE inhibitors such as MLN4924 and TAS4464 currently entered into clinical trials for cancer therapy, particularly for hematological tumors. This review explains the relationships between NEDDylation and cancers, structural characteristics of NAE and multistep mechanisms of NEDD8 activation by NAE. In addition, the potential approaches to discover NAE inhibitors and detailed pharmacological mechanisms of NAE inhibitors in the clinical stage are explored in depth. Importantly, we reasonably investigate the challenges of NAE inhibitors for cancer therapy and possible development directions of NAE-targeting drugs in the future.
Topics: Humans; Ubiquitins; Neoplasms; Antineoplastic Agents; NEDD8 Protein
PubMed: 37525282
DOI: 10.1186/s13045-023-01485-7 -
Biochemical Pharmacology Sep 2023Acute myeloid leukemia (AML) is characterized by impaired differentiation and indefinite proliferation of abnormal myeloid progenitors. Although differentiating agents... (Review)
Review
Acute myeloid leukemia (AML) is characterized by impaired differentiation and indefinite proliferation of abnormal myeloid progenitors. Although differentiating agents were deemed to revolutionize AML therapy, most treated non-APL AML patients are refractory or relapse. According to cancer stem cell model, leukemia-initiating cells are the root cause of relapse given their unidirectional potential to generate differentiated AML blasts. Nonetheless, accumulating evidences emphasize the de-differentiation plasticity and leukemogenic potential of mature AML blasts and the frailty of targeting leukemic stem cells per se. This review critically discusses the potential and challenges of (lessons learnt from) conventional and novel differentiating agents in AML therapy. Although differentiating agents might hold promise, they should be exploited within the context of a rationale combination regimen eradicating all maturation/differentiation states of AML cells. The results of the routinely used immunophenotypic markers and/or morphological analyses of differentiation should be carefully interpreted given their propensity to underestimate AML burden.
Topics: Humans; Leukemia, Myeloid, Acute; Antineoplastic Agents; Cell Differentiation; Neoplastic Stem Cells
PubMed: 37506924
DOI: 10.1016/j.bcp.2023.115709 -
Journal of Drug Targeting Dec 2023Pancreatic cancer (PC) is a common malignant tumour in the digestive system. Due to the lack of sensitive diagnostic markers, strong metastasis ability, and resistance... (Review)
Review
Pancreatic cancer (PC) is a common malignant tumour in the digestive system. Due to the lack of sensitive diagnostic markers, strong metastasis ability, and resistance to anti-cancer drugs, the prognosis of PC is inferior. In the past decades, increasing evidence has indicated that the development of PC is closely related to various signalling pathways. With the exploration of RAS-driven, epidermal growth factor receptor, Hedgehog, NF-κB, TGF-β, and NOTCH signalling pathways, breakthroughs have been made to explore the mechanism of pancreatic carcinogenesis, as well as the novel therapies. In this review, we discussed the signalling pathways involved in PC and summarised current targeted agents in the treatment of PC. Furthermore, opportunities and challenges in the exploration of potential therapies targeting signalling pathways were also highlighted.
Topics: Humans; Pancreatic Neoplasms; Signal Transduction; Antineoplastic Agents; Prognosis
PubMed: 37869884
DOI: 10.1080/1061186X.2023.2274806 -
Molecular Cancer May 2024Ferroptosis is a type of regulated cell death characterized by iron accumulation and uncontrolled lipid peroxidation, leading to plasma membrane rupture and... (Review)
Review
Ferroptosis is a type of regulated cell death characterized by iron accumulation and uncontrolled lipid peroxidation, leading to plasma membrane rupture and intracellular content release. Originally investigated as a targeted therapy for cancer cells carrying oncogenic RAS mutations, ferroptosis induction now exhibits potential to complement chemotherapy, immunotherapy, and radiotherapy in various cancer types. However, it can lead to side effects, including immune cell death, bone marrow impairment, liver and kidney damage, cachexia (severe weight loss and muscle wasting), and secondary tumorigenesis. In this review, we discuss the advantages and offer an overview of the diverse range of documented side effects. Furthermore, we examine the underlying mechanisms and explore potential strategies for side effect mitigation.
Topics: Humans; Neoplasms; Ferroptosis; Animals; Antineoplastic Agents
PubMed: 38702722
DOI: 10.1186/s12943-024-01999-9 -
Bioorganic Chemistry Oct 2023Heat shock protein 90, also known as Hsp90, is an extensively preserved molecular chaperone that performs a critical function in organizing various biological pathways... (Review)
Review
Heat shock protein 90, also known as Hsp90, is an extensively preserved molecular chaperone that performs a critical function in organizing various biological pathways and cellular operations. As a potential drug target, Hsp90 is closely linked to cancer. Hsp90 inhibitors are a class of drugs that have been extensively studied in preclinical models and have shown promise in a variety of diseases, especially cancer. However, Hsp90 inhibitors have encountered several challenges in clinical development, such as low efficacy, toxicity, or drug resistance, few Hsp90 small molecule inhibitors have been approved worldwide. Nonetheless, combining Hsp90 inhibitors with other tumor inhibitors, such as HDAC inhibitors, tubulin inhibitors, and Topo II inhibitors, has been shown to have synergistic antitumor effects. Consequently, the development of Hsp90 dual-target inhibitors is an effective strategy in cancer treatment, as it enhances potency while reducing drug resistance. This article provides an overview of Hsp90's domain structure and biological functions, as well as a discussion of the design, discovery, and structure-activity relationships of Hsp90 dual inhibitors, aiming to provide insights into clinical drug research from a medicinal chemistry perspective and discover novel Hsp90 dual inhibitors.
Topics: Humans; Neoplasms; Antineoplastic Agents; HSP90 Heat-Shock Proteins; Structure-Activity Relationship; Drug Delivery Systems
PubMed: 37467620
DOI: 10.1016/j.bioorg.2023.106721 -
Pharmacology & Therapeutics Jun 2024DNA methylation is a critical component of gene regulation and plays an important role in the development of cancer. Hypermethylation of tumor suppressor genes and... (Review)
Review
DNA methylation is a critical component of gene regulation and plays an important role in the development of cancer. Hypermethylation of tumor suppressor genes and silencing of DNA repair pathways facilitate uncontrolled cell growth and synergize with oncogenic mutations to perpetuate cancer phenotypes. Additionally, aberrant DNA methylation hinders immune responses crucial for antitumor immunity. Thus, inhibiting dysregulated DNA methylation is a promising cancer therapy. Pharmacologic inhibition of DNA methylation reactivates silenced tumor suppressors and bolster immune responses through induction of viral mimicry. Now, with the advent of immunotherapies and discovery of the immune-modulatory effects of DNA methylation inhibitors, there is great interest in understanding how targeting DNA methylation in combination with other therapies can enhance antitumor immunity. Here, we describe the role of aberrant DNA methylation in cancer and mechanisms by which it promotes tumorigenesis and modulates immune responses. Finally, we review the initial discoveries and ongoing efforts to target DNA methylation as a cancer therapeutic.
Topics: Humans; DNA Methylation; Neoplasms; Animals; Antineoplastic Agents; Molecular Targeted Therapy; Immunotherapy
PubMed: 38570075
DOI: 10.1016/j.pharmthera.2024.108640 -
Phytotherapy Research : PTR Feb 2024Natural products have played a significant role throughout history in the prevention and treatment of numerous diseases, particularly cancers. As a natural product... (Review)
Review
Natural products have played a significant role throughout history in the prevention and treatment of numerous diseases, particularly cancers. As a natural product primarily derived from various medicinal plants in the Withania genus, withanolides have been shown in several studies to exhibit potential activities in cancer treatment. Consequently, understanding the molecular mechanism of withanolides could herald the discovery of new anticancer agents. Withanolides have been studied widely, especially in the last 20 years, and attracted the attention of numerous researchers. Currently, over 1200 withanolides have been classified, with approximately a quarter of them having been reported in the literature to be able to modulate the survival and death of cancer cells through multiple avenues. To what extent, though, has the anticancer effects of these compounds been studied? How far are they from being developed into clinical drugs? What are their potential, characteristic features, and challenges? In this review, we elaborate on the current knowledge of natural compounds belonging to this class and provide an overview of their natural sources, anticancer activity, mechanism of action, molecular targets, and implications for anticancer drug research. In addition, direct targets and clinical research to guide the design and implementation of future preclinical and clinical studies to accelerate the application of withanolides have been highlighted.
Topics: Humans; Withanolides; Antineoplastic Agents; Neoplasms; Withania; Plants, Medicinal
PubMed: 38176694
DOI: 10.1002/ptr.8090