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Introduction: Identifying effective cancer drugs remains an inefficient process. Drug efficacy in traditional preclinical cancer models translates poorly into therapy in the clinic. Implementation of preclinical models that incorporate the tumor microenvironment (TME) is needed to improve selection of active drugs prior to clinical trials.
Areas Covered: Progression of cancer results from the behavior of cancer cells in concert with the host's histopathological background. Nonetheless, complex preclinical models with a relevant microenvironment have yet to become an integral part of drug development. This review discusses existing models and provides a synopsis of active areas of cancer drug development where implementation would be of value. Their contribution to finding therapeutics in immune oncology, angiogenesis, regulated cell death and targeting tumor fibroblasts as well as optimization of drug delivery, combination therapy, and biomarkers of efficacy is considered.
Expert Opinion: Complex tumor models in vitro (CTMIVs) that mimic the organotypic architecture of neoplastic tumors have boosted research into TME influence on traditional cytoreductive chemotherapy as well as the detection of specific TME targets. Despite advances in technical prowess, CTMIVs can only address specific aspects of cancer pathophysiology.
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http://dx.doi.org/10.1080/17460441.2023.2216016 | DOI Listing |
J Biomed Sci
September 2025
Division of Gastroenterology, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Oncometabolites are aberrant metabolic byproducts that arise from mutations in enzymes of the tricarboxylic acid (TCA) cycle or related metabolic pathways and play central roles in tumor progression and immune evasion. Among these, 2-hydroxyglutarate (2-HG), succinate, and fumarate are the most well-characterized, acting as competitive inhibitors of α-ketoglutarate-dependent dioxygenases to alter DNA and histone methylation, cellular differentiation, and hypoxia signaling. More recently, itaconate, an immunometabolite predominantly produced by activated macrophages, has been recognized for its dual roles in modulating inflammation and tumor immunity.
View Article and Find Full Text PDFOncogene
September 2025
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Pancreatic cancer is a highly aggressive malignancy with a dismal prognosis, characterized by a complex tumor microenvironment that promotes immunosuppression and limits the efficacy of immune checkpoint blockade (ICB) therapy. Fibroblast activation protein (FAP) is overexpressed in the tumor stroma and represents a promising target for therapeutic intervention. Here, we developed a novel antibody-drug conjugate (ADC) targeting FAP, and investigated its anti-tumor activity and ability to enhance ICB efficacy in pancreatic cancer.
View Article and Find Full Text PDFUrol Oncol
September 2025
Nutritional, Genes and Human Disease Laboratory, Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh. Electronic address:
Background: Understanding the mutational landscape is critical for elucidating the molecular mechanisms driving cancer progression. This study aimed to profile somatic mutations in bladder cancer patients (N=7) from Bangladesh to provide insights into the genetic alterations underlying this malignancy.
Methods: We performed targeted sequencing of 50 oncogenes and tumor suppressor genes using the Ion AmpliSeq Cancer Hotspot Panel v2 on tumor and matched blood samples from seven bladder cancer patients.
J Immunother Cancer
September 2025
Pharmaceutical Sciences, Washington State University, Spokane, Washington, USA
Prostate cancer (PC) is notoriously known for exhibiting an immunologically cold phenotype in the tumor immune microenvironment (TIME), leading to the need for interventions to enhance immunotherapy efficacy. Recent findings by Zhao in the identified stromal monoamine oxidase A (MAOA), a key enzyme that degrades monoamine neurotransmitters and plays a role in the neuroendocrine system, as a critical regulator of the immune response to PC. Altering MAOA levels in myofibroblastic cancer-associated fibroblasts, either genetically or pharmacologically, can reprogram PC's TIME to modulate CD8 T cell-mediated cytotoxicity through the WNT5A-Ca²-NFATC1 signaling axis, highlighting the stromal influences on CD8 T cell cytotoxic activity within the TIME.
View Article and Find Full Text PDFMethods Cell Biol
September 2025
LR18ES03 Laboratory of Neurophysiology, Cellular Physiopathology and Valorisation of Biomolecules, Faculty of Science of Tunis, University Tunis El Manar, Tunis, Tunisia. Electronic address:
Breast cancer (BC) represents a major socio-economic challenge worldwide due to its high morbidity and mortality rates. Despite various therapeutic strategies, the heterogeneity of breast cancer and the resistance of tumour cells often lead to treatment failure. Consequently, the use of animal models of BC is crucial for understanding the cellular and molecular mechanisms involved in the different stages of carcinogenesis and for screening new drugs to assess their efficacy, potential safety and side effects.
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