The development of new anticancer therapies tends to be very slow. Although their impact on potential candidates is confirmed in preclinical studies, ∼95 % of these new therapies are not approved when tested in clinical trials. One of the main reasons for this is the lack of accurate preclinical models. In this context, there are different patient-derived models, which have emerged as a powerful oncological tool: patient-derived xenografts (PDXs), patient-derived organoids (PDOs), and patient-derived cells (PDCs). Although all these models are widely applied, PDXs, which are created by engraftment of patient tumor tissues into mice, is considered more reliable. In fundamental research, the PDX model is used to evaluate drug-sensitive markers and, in clinical practice, to select a personalized therapeutic strategy. Melatonin is of particular importance in the development of innovative cancer treatments due to its oncostatic impact and lack of adverse effects. However, the literature regarding the oncostatic effect of melatonin in patient-derived tumor models is scant. This review aims to describe the important role of patient-derived models in the development of anticancer treatments, focusing, in particular, on PDX models, as well as their use in cancer research. This review also summarizes the existing literature on the anti-tumoral effect of melatonin in patient-derived models in order to propose future anti-neoplastic clinical applications.
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http://dx.doi.org/10.1016/j.biopha.2023.115581 | DOI Listing |
Mol Cancer Ther
January 2025
Albert Einstein College of Medicine, Bronx, NY, United States.
Osteosarcoma (OS) is the most common primary malignant bone tumor in childhood. Patients who present with metastatic disease at diagnosis or relapse have a very poor prognosis, and this has not changed over the past four decades. The Wnt signaling pathway plays a role in regulating osteogenesis and is implicated in OS pathogenesis.
View Article and Find Full Text PDFHaematologica
January 2025
University Clinic Tübingen, Department for Internal Medicine II, University of Tübingen, Tübingen, Germany; German Cancer Consortium (DKTK), partner site Tübingen, a partnership between DKFZ and University Hospital Tübingen.
In acute myeloid leukemia (AML), leukemogenesis depends on cell-intrinsic genetic aberrations and thus, studies on AML require investigations in an in vivo setting as provided by patient derived xenografts (PDX) models. Here we report that, next to leukemic cell characteristics, recipient sex highly influences the outgrowth of AML cells in PDX models, with females being much better repopulated than males in primary as well as secondary transplantation assays. Testosterone may be the more important player since, strikingly, better engraftment was seen in castrated versus control male recipients, while ovariectomy did not significantly impair engraftment in females.
View Article and Find Full Text PDFExp Ther Med
February 2025
Department of General Surgical Science, Division of Hepatobiliary and Pancreatic Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
The present study aimed to investigate the role of a recombinant protein based on human collagen type I (RCPhC1) as a scaffold in maintaining the human tumor microenvironment within a patient-derived tumor xenograft (PDTX) model. RCPhC1, synthesized under animal component-free conditions, was explored for its potential to support the human-specific stroma associated with tumor growth. PDTX models were established using resected colorectal cancer liver metastasis specimens, and stromal cell populations from humans and mice were compared using three scaffolds: No scaffold (control), Matrigel and recombinant human collagen type I, across two passages.
View Article and Find Full Text PDFJ Exp Clin Cancer Res
January 2025
Cancer Biology Graduate Program, Wayne State University School of Medicine, Detroit, MI, 48201, USA.
Background: Venetoclax + azacitidine is a frontline treatment for older adult acute myeloid leukemia (AML) patients and a salvage therapy for relapsed/refractory patients who have been treated with intensive chemotherapy. While this is an important treatment option, many patients fail to achieve complete remission and of those that do, majority relapse. Leukemia stem cells (LSCs) are believed to be responsible for AML relapse and can be targeted through oxidative phosphorylation reduction.
View Article and Find Full Text PDFMol Cancer
January 2025
Foshan Maternity and Child Healthcare Hospital; School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 515150, China.
Background: Intratumor-resident bacteria represent an integral component of the tumor microenvironment (TME). Microbial dysbiosis, which refers to an imbalance in the bacterial composition and bacterial metabolic activities, plays an important role in regulating breast cancer development and progression. However, the impact of specific intratumor-resident bacteria on tumor progression and their underlying mechanisms remain elusive.
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