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Tumor cell-derived N-acetyl-aspartyl-glutamate reshapes the tumor microenvironment to facilitate breast cancer metastasis.
Sci Bull (Beijing)
December 2024
Fudan University Shanghai Cancer Center & Institutes of Biomedical Sciences; State Key Laboratory of Genetic Engineering; Cancer Institutes; Department of Oncology; Key Laboratory of Breast Cancer in Shanghai; The Shanghai Key Laboratory of Medical Epigenetics; Shanghai Key Laboratory of Radiation Oncology; The International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology; Shanghai Medical College; Fudan University, Shanghai 200032, China; Jinfeng Laboratory, Chongqing 401329, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing 211166, China. Electronic address:
Neurotransmitters are increasingly recognized to play important roles in limiting anti-tumor immunity. N-acetyl-aspartyl-glutamate (NAAG) has been extensively studied in neurological disorders; however, its potential role in restricting anti-tumor immunity has not been investigated. Here, we demonstrated that NAAG or its synthetase RimK-like family member B (RIMKLB) significantly disrupted anti-tumor immunity by rewiring the myeloid progenitor differentiation of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), which in turn promoted breast cancer growth and metastasis.
View Article and Find Full Text PDFThe RAGE Inhibitor TTP488 (Azeliragon) Demonstrates Anti-Tumor Activity and Enhances the Efficacy of Radiation Therapy in Pancreatic Cancer Cell Lines.
Cancers (Basel)
December 2024
Department of Radiation Oncology, Corewell Health William Beaumont University Hospital, Royal Oak, MI 48076, USA.
Pancreatic cancer is the third leading cause of cancer-related mortality in the United States, with rising incidence and mortality. The receptor for advanced glycation end products (RAGE) and its ligands significantly contribute to pancreatic cancer progression by enhancing cell proliferation, fostering treatment resistance, and promoting a pro-tumor microenvironment via activation of the nuclear factor-kappa B (NF-κB) signaling pathways. This study validated pathway activation in human pancreatic cancer and evaluated the therapeutic efficacy of TTP488 (Azeliragon), a small-molecule RAGE inhibitor, alone and in combination with radiation therapy (RT) in preclinical models of pancreatic cancer.
View Article and Find Full Text PDFMyeloid-derived suppressor cells (MDSCs) in the tumor microenvironment and their targeting in cancer therapy.
Mol Cancer
January 2025
Laboratory of Oncology, Basic Research Center, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, Jiangsu, China.
The advent of immunotherapy represents a significant breakthrough in cancer treatment, with immune checkpoint inhibitors (ICIs) targeting PD-1 and CTLA-4 demonstrating remarkable therapeutic efficacy. However, patient responses to immunotherapy vary significantly, with immunosuppression within the tumor microenvironment (TME) being a critical factor influencing this variability. Immunosuppression plays a pivotal role in regulating cancer progression, metastasis, and reducing the success rates of immunotherapy.
View Article and Find Full Text PDFTargeted inhibition of Aurora kinase A promotes immune checkpoint inhibition efficacy in human papillomavirus-driven cancers.
J Immunother Cancer
January 2025
Department of Thoracic, Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Background: Human papillomavirus (HPV)-driven cancers include head and neck squamous cell carcinoma and cervical cancer and represent approximately 5% of all cancer cases worldwide. Standard-of-care chemotherapy, radiotherapy, and immune checkpoint inhibitors (ICIs) are associated with adverse effects and limited responses in patients with HPV-driven cancers. The integration of targeted therapies with ICIs may improve outcomes.
View Article and Find Full Text PDFImmunotherapy in the Battle Against Bone Metastases: Mechanisms and Emerging Treatments.
Pharmaceuticals (Basel)
November 2024
Department of Anatomy and Genetics, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia.
Bone metastases are a prevalent complication in advanced cancers, particularly in breast, prostate, and lung cancers, and are associated with severe skeletal-related events (SREs), including fractures, spinal cord compression, and debilitating pain. Conventional bone-targeted treatments like bisphosphonates and RANKL inhibitors (denosumab) reduce osteoclast-mediated bone resorption but do not directly impact tumor progression within the bone. This review focuses on examining the growing potential of immunotherapy in targeting the unique challenges posed by bone metastases.
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