MDM2 Inhibitors for Cancer Therapy: The Past, Present, and Future
In conclusion, targeting MDM2 remains a promising treatment approach, and targeting MDM2 for protein degradation represents a novel strategy to downregulate MDM2 without the side effects of the existing agents blocking p53-MDM2 binding. Additional preclinical and clinical investigations are needed to finally realize the full potential of MDM2 inhibition in treating cancer and other chronic diseases where MDM2 has been implicated. SIGNIFICANCE STATEMENT: Overexpression/amplification of the MDM2 oncogene has been detected in various human cancers and is associated with disease progression, treatment resistance, and poor pati...
Source: Pharmacological Reviews - May 2, 2024 Category: Drugs & Pharmacology Authors: Wei Wang Najah Albadari Yi Du Josef F Fowler Hannah T Sang Wa Xian Frank McKeon Wei Li Jia Zhou Ruiwen Zhang Source Type: research
Mitochondria-targeting metallodrugs for cancer therapy: perspectives from cell death modes
ChemMedChem. 2024 May 2:e202400120. doi: 10.1002/cmdc.202400120. Online ahead of print.ABSTRACTMitochondria, recognized as the cellular powerhouses, are indispensable organelles responsible for crucial cellular processes, such as energy metabolism, material synthesis, and signaling transduction. Their intricate involvement in a broad spectrum of diseases, particularly cancer, has propelled the exploration of mitochondria-targeting treatment as a promising strategy for cancer therapy. Since the groundbreaking discovery of cisplatin, the trajectory of research on the development of metal complexes have been marked by continu...
Source: ChemMedChem - May 2, 2024 Category: Chemistry Authors: Zhi Su Hao-Ming Li Meng-Meng Wang Yan Su Hong-Bao Fang Source Type: research
Targeting leucine-rich PPR motif-containing protein/LRPPRC by 5,7,4'-trimethoxyflavone suppresses esophageal squamous cell carcinoma progression
In this study, genes associated with JAK2, STAT3, and MYC were analyzed, and potential target genes were selected. Leucine-rich PPR motif-containing protein (LRPPRC) whose function and regulation are not fully understood, emerged as one of top 3 genes in terms of RNA epigenetic modification. Here, we demonstrate LRPPRC may be an independent prognostic indicator besides JAK2, STAT3, and MYC. Mechanistically, LRPPRC impairs N6-methyladenosine (m6A) modification of JAK2, STAT3, and MYC to facilitate nuclear mRNA export and expression. Meanwhile, excess LRPPRC act as a scaffold protein binding to JAK2 and STAT3 to enhance stab...
Source: International Journal of Biological Macromolecules - May 2, 2024 Category: Biochemistry Authors: Hui Liu Yubing Zhou Mangaladoss Fredimoses Peijia Niu Yunxiao Ge Rui Wu Tingting Liu Pan Li Yang Shi Yaqian Shi Kangdong Liu Zigang Dong Source Type: research
Verteporfin inhibits TGF- β signaling by disrupting the Smad2/3-Smad4 interaction
In this study, we focus on the Smad2/3-Smad4 complex, a key component in TGF-β signaling transduction, as a potential target for cancer therapy. Through a phase-separated condensate-aided biomolecular interaction system, we identified verteporfin (VP) as a small-molecule inhibitor that specifically targets the Smad2/3-Smad4 interaction. VP effectively disrupted the interaction between Smad2/3 and Smad4 and thereby inhibited canonical TGF-β signaling, but not the interaction between Smad1 and Smad4 in BMP signaling. Furthermore, VP exhibited inhibitory effects on TGF-β-induced epithelial-mesenchymal transition and cell m...
Source: Mol Biol Cell - May 2, 2024 Category: Molecular Biology Authors: Junxiu Nong Shengqiang Shen Fan Hong Fan Xiao Lingtian Meng Pilong Li Xiaoguang Lei Ye-Guang Chen Source Type: research
Targeting tumor ‑associated macrophages: Critical players in tumor progression and therapeutic strategies (Review)
Int J Oncol. 2024 Jun;64(6):60. doi: 10.3892/ijo.2024.5648. Epub 2024 May 2.ABSTRACTTumor‑associated macrophages (TAMs) are essential components of the tumor microenvironment (TME) and display phenotypic heterogeneity and plasticity associated with the stimulation of bioactive molecules within the TME. TAMs predominantly exhibit tumor‑promoting phenotypes involved in tumor progression, such as tumor angiogenesis, metastasis, immunosuppression and resistance to therapies. In addition, TAMs have the potential to regulate the cytotoxic elimination and phagocytosis of cancer cells and interact with other immune cells to en...
Source: International Journal of Oncology - May 2, 2024 Category: Cancer & Oncology Authors: Pengfei Su Ou Li Kun Ke Zhichen Jiang Jianzhang Wu Yuanyu Wang Yiping Mou Weiwei Jin Source Type: research
The crosstalk between glucose metabolism and telomerase regulation in cancer
Biomed Pharmacother. 2024 May 1;175:116643. doi: 10.1016/j.biopha.2024.116643. Online ahead of print.ABSTRACTAccumulated alterations in metabolic control provide energy and anabolic demands for enhanced cancer cell proliferation. Exemplified by the Warburg effect, changes in glucose metabolism during cancer progression are widely recognized as a characteristic of metabolic disorders. Since telomerases are a vital factor in maintaining DNA integrity and stability, any damage threatening telomerases could have a severe impact on DNA and, subsequently, whole-cell homeostasis. However, it remains unclear whether the regulation...
Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - May 2, 2024 Category: Drugs & Pharmacology Authors: Mingrui Huang Mingdi Liu Ruijia Wang Yifan Man Honglan Zhou Zhi-Xiang Xu Yishu Wang Source Type: research
MDM2 Inhibitors for Cancer Therapy: The Past, Present, and Future
In conclusion, targeting MDM2 remains a promising treatment approach, and targeting MDM2 for protein degradation represents a novel strategy to downregulate MDM2 without the side effects of the existing agents blocking p53-MDM2 binding. Additional preclinical and clinical investigations are needed to finally realize the full potential of MDM2 inhibition in treating cancer and other chronic diseases where MDM2 has been implicated. SIGNIFICANCE STATEMENT: Overexpression/amplification of the MDM2 oncogene has been detected in various human cancers and is associated with disease progression, treatment resistance, and poor pati...
Source: Pharmacological Reviews - May 2, 2024 Category: Drugs & Pharmacology Authors: Wei Wang Najah Albadari Yi Du Josef F Fowler Hannah T Sang Wa Xian Frank McKeon Wei Li Jia Zhou Ruiwen Zhang Source Type: research
Mitochondria-targeting metallodrugs for cancer therapy: perspectives from cell death modes
ChemMedChem. 2024 May 2:e202400120. doi: 10.1002/cmdc.202400120. Online ahead of print.ABSTRACTMitochondria, recognized as the cellular powerhouses, are indispensable organelles responsible for crucial cellular processes, such as energy metabolism, material synthesis, and signaling transduction. Their intricate involvement in a broad spectrum of diseases, particularly cancer, has propelled the exploration of mitochondria-targeting treatment as a promising strategy for cancer therapy. Since the groundbreaking discovery of cisplatin, the trajectory of research on the development of metal complexes have been marked by continu...
Source: ChemMedChem - May 2, 2024 Category: Chemistry Authors: Zhi Su Hao-Ming Li Meng-Meng Wang Yan Su Hong-Bao Fang Source Type: research
Targeting tumor ‑associated macrophages: Critical players in tumor progression and therapeutic strategies (Review)
Int J Oncol. 2024 Jun;64(6):60. doi: 10.3892/ijo.2024.5648. Epub 2024 May 2.ABSTRACTTumor‑associated macrophages (TAMs) are essential components of the tumor microenvironment (TME) and display phenotypic heterogeneity and plasticity associated with the stimulation of bioactive molecules within the TME. TAMs predominantly exhibit tumor‑promoting phenotypes involved in tumor progression, such as tumor angiogenesis, metastasis, immunosuppression and resistance to therapies. In addition, TAMs have the potential to regulate the cytotoxic elimination and phagocytosis of cancer cells and interact with other immune cells to en...
Source: International Journal of Oncology - May 2, 2024 Category: Cancer & Oncology Authors: Pengfei Su Ou Li Kun Ke Zhichen Jiang Jianzhang Wu Yuanyu Wang Yiping Mou Weiwei Jin Source Type: research
MDM2 Inhibitors for Cancer Therapy: The Past, Present, and Future
In conclusion, targeting MDM2 remains a promising treatment approach, and targeting MDM2 for protein degradation represents a novel strategy to downregulate MDM2 without the side effects of the existing agents blocking p53-MDM2 binding. Additional preclinical and clinical investigations are needed to finally realize the full potential of MDM2 inhibition in treating cancer and other chronic diseases where MDM2 has been implicated. SIGNIFICANCE STATEMENT: Overexpression/amplification of the MDM2 oncogene has been detected in various human cancers and is associated with disease progression, treatment resistance, and poor pati...
Source: Pharmacological Reviews - May 2, 2024 Category: Drugs & Pharmacology Authors: Wei Wang Najah Albadari Yi Du Josef F Fowler Hannah T Sang Wa Xian Frank McKeon Wei Li Jia Zhou Ruiwen Zhang Source Type: research
Mitochondria-targeting metallodrugs for cancer therapy: perspectives from cell death modes
ChemMedChem. 2024 May 2:e202400120. doi: 10.1002/cmdc.202400120. Online ahead of print.ABSTRACTMitochondria, recognized as the cellular powerhouses, are indispensable organelles responsible for crucial cellular processes, such as energy metabolism, material synthesis, and signaling transduction. Their intricate involvement in a broad spectrum of diseases, particularly cancer, has propelled the exploration of mitochondria-targeting treatment as a promising strategy for cancer therapy. Since the groundbreaking discovery of cisplatin, the trajectory of research on the development of metal complexes have been marked by continu...
Source: ChemMedChem - May 2, 2024 Category: Chemistry Authors: Zhi Su Hao-Ming Li Meng-Meng Wang Yan Su Hong-Bao Fang Source Type: research
ROS ‐Responsive and Self‐Tumor Curing Methionine Polymer Library Based Nanoparticles with Self‐Accelerated Drug Release and Hydrophobicity/Hydrophilicity Switching Capability for Enhanced Cancer Therapy
A small library of methionine-based polymers (Met-P) with programmed structure and reactive oxygen species (ROS) –responsive properties are developed for tumor therapy. The Met-P could achieve the transformation from a hydrophobic to a hydrophilic state in the tumor microenvironment with a high ROS level, triggering the self-accelerated release of drug. More interestingly, the blank Met-P nanocarriers displa yed an obvious self-tumor inhibiting efficacy. AbstractThe applications of amino acid-based polymers are impeded by their limited structure and functions. Herein, a small library of methionine-based polymers (Met-P) ...
Source: Small - May 2, 2024 Category: Nanotechnology Authors: Jie Liu,
Xinru You,
Liying Wang,
Jianwen Zeng,
Hai Huang,
Jun Wu Tags: Research Article Source Type: research
Molecules, Vol. 29, Pages 2110: Metabolic Rewiring in Cancer: Small Molecule Inhibitors in Colorectal Cancer Therapy
Regina
Alterations in cellular metabolism, such as dysregulation in glycolysis, lipid metabolism, and glutaminolysis in response to hypoxic and low-nutrient conditions within the tumor microenvironment, are well-recognized hallmarks of cancer. Therefore, understanding the interplay between aerobic glycolysis, lipid metabolism, and glutaminolysis is crucial for developing effective metabolism-based therapies for cancer, particularly in the context of colorectal cancer (CRC). In this regard, the present review explores the complex field of metabolic reprogramming in tumorigenesis and progression, providing insights into...
Source: Molecules - May 2, 2024 Category: Chemistry Authors: Domiziana Masci Michela Puxeddu Romano Silvestri Giuseppe La Regina Tags: Review Source Type: research
Neutrophil-activating secretome characterizes palbociclib-induced senescence of breast cancer cells
In this study, we investigate the induction of cellular senescence in breast cancer cells and the subsequent immunomodulatory effects on neutrophils using the CDK4/6 inhibitor palbociclib, which is approved for the treatment of breast cancer and is under intense investigation for additional malignancies. Our research demonstrates that palbociclib induces a reversible form of senescence endowed with an inflammatory secretome capable of recruiting and activating neutrophils, in part through the action of interleukin-8 and acute-phase serum amyloid A1. The activation of neutrophils is accompanied by the release of neutrophil ...
Source: Cancer Immunology, Immunotherapy - May 2, 2024 Category: Cancer & Oncology Source Type: research
Key residues in the VDAC2-BAK complex can be targeted to modulate apoptosis
by Zheng Yuan, Mark F. van Delft, Mark Xiang Li, Fransisca Sumardy, Brian J. Smith, David C. S. Huang, Guillaume Lessene, Yelena Khakam, Ruitao Jin, Sitong He, Nicholas A. Smith, Richard W. Birkinshaw, Peter E. Czabotar, Grant Dewson
BAK and BAX execute intrinsic apoptosis by permeabilising the mitochondrial outer membrane. Their activity is regulated through interactions with pro-survival BCL-2 family proteins and with non-BCL-2 proteins including the mitochondrial porin VDAC2. VDAC2 is important for bringing both BAK and BAX to mitochondria where they execute their apoptotic function. Despite this important function in ...
Source: PLoS Biology: Archived Table of Contents - May 2, 2024 Category: Biology Authors: Zheng Yuan Source Type: research
