The year 2019 witnessed the first approval of an immune checkpoint inhibitor (ICI) for the management of triple negative breast cancers (TNBC) that are metastatic and programmed death ligand (PD)-L1 positive. Extensive research has focused on testing ICI-based combinatorial strategies, with the ultimate goal of enhancing the response of breast tumors to immunotherapy to increase the number of breast cancer patients benefiting from this transformative treatment. The promising investigational strategies included immunotherapy combinations with monoclonal antibodies (mAbs) against human epidermal growth factor receptor (HER)-2 for the HER2 + tumors versus cyclin-dependent kinase (CDK)4/6 inhibitors in the estrogen receptor (ER) + disease. Multiple approaches are showing signals of success in advanced TNBC include employing Poly (ADP-ribose) polymerase (PARP) inhibitors, tyrosine kinase inhibitors, MEK inhibitors, phosphatidylinositol 3‑kinase (PI3K)/protein kinase B (AKT) signaling inhibitors or inhibitors of adenosine receptor, in combination with the classical PD-1/PD-L1 immune checkpoint inhibitors. Co-treatment with chemotherapy, high intensity focused ultrasound (HIFU) or interleukin-2-βɣ agonist have also produced promising outcomes. This review highlights the latest combinatorial strategies under development for overcoming cancer immune evasion and enhancing the percentage of immunotherapy responders in the different subsets of advanced breast cancers.
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http://dx.doi.org/10.1007/s12094-021-02613-w | DOI Listing |
Adv Drug Deliv Rev
January 2025
School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University 637459 Singapore; Critical Analytics for Manufacturing Personalized-Medicine Interdisciplinary Research Group, Singapore-MIT Alliance for Research & Technology, Campus for Research Excellence and Technological Enterprise 138602 Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University 308232 Singapore; School of Materials Science and Engineering 639798 Singapore; National Neuroscience Institute, 11 Jalan Tan Tock Seng 308433 Singapore. Electronic address:
Combinatorial treatments integrating cells and biomolecules within scaffolds have been investigated to address the multifactorial nature of spinal cord injury (SCI). Current regenerative treatments have been ineffective as they do not consider the spatial positions of various cell types to effectively form functional neural pathways. Emulating the complex heterogeneity of cells in the native spinal cord requires translating the existing biological understanding of spatial patterning in neural development, as well as the influence of biomolecule and mechanical patterning on regional specification and axonal regeneration, to engineer a scaffold for spinal cord regeneration.
View Article and Find Full Text PDFJ Endocr Soc
January 2025
Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX3 7LD, UK.
Purpose: To describe diagnostic approaches and management strategies for patients with primary hyperparathyroidism (PHPT) and recent fracture in England.
Methods: We developed a survey based on a patient at high fracture risk and a new diagnosis of probable PHPT. The survey was circulated among 50 secondary care professionals identified by the Society for Endocrinology Calcium and Bone special interest group.
Sci Rep
January 2025
Laboratoire de Biophysique et Evolution, UMR CNRS-ESPCI 8231 Chimie Biologie Innovation, PSL University, Paris, France.
Synergistic drug combination screening is a promising strategy in drug discovery, but it involves navigating a costly and complex search space. While AI, particularly deep learning, has advanced synergy predictions, its effectiveness is limited by the low occurrence of synergistic drug pairs. Active learning, which integrates experimental testing into the learning process, has been proposed to address this challenge.
View Article and Find Full Text PDFMol Cancer Ther
January 2025
University of Michigan-Ann Arbor, Ann Arbor, MI, United States.
Up to 90% of high-grade serous ovarian cancer (HGSC) patients will develop resistance to platinum-based chemotherapy, posing substantial therapeutic challenges due to a lack of universally druggable targets. Leveraging BenevolentAI's AI-driven approach to target discovery, we screened potential AI-predicted therapeutic targets mapped to unapproved tool compounds in patient-derived 3D models. This identified TNIK, which is modulated by NCB-0846, as a novel target for platinum-resistant HGSC.
View Article and Find Full Text PDFFront Cell Dev Biol
January 2025
Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Essen, Germany.
Consolidation with PD-1/PD-L1-based immune checkpoint blockade after concurrent platinum-based chemo-radiotherapy has become the new standard of care for advanced stage III unresectable non-small cell lung cancer (NSCLC) patients. In order to further improve therapy outcomes, innovative combinatorial treatment strategies aim to target additional immunosuppressive barriers in the tumor microenvironment such as the CD73/adenosine pathway. CD73 and adenosine are known as crucial endogenous regulators of lung homeostasis and inflammation, but also contribute to an immunosuppressive tumor microenvironment.
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