Publicaties

Despite poor response rates and dose-limiting cardiotoxicity, doxorubicin (doxo) remains the standard-of-care for patients with advanced soft tissue sarcoma. We evaluated the efficacy of two tetrapeptidic doxo prodrugs (PhAc-ALGP-Dox or CBR-049 and CBR-050) that are locally activated by enzymes expressed in the tumor environment, in ten sarcoma patient-derived xenografts. Xenograft models were selected based on expression of the main activating ...

BACKGROUND: Soft tissue sarcoma (STS) comprises a family of rare, heterogeneous tumors of mesenchymal origin. Single-agent doxorubicin remains the first-line standard-of-care treatment for advanced and inoperable STS, but response rates are only around 15%. In 2016, phase Ib/II clinical trial results reported an overall survival benefit of 11.8 months when combining doxorubicin and the platelet-derived growth factor receptor alpha ...

There is a lack of well-characterized models for pancreatic ductal adenocarcinoma (PDAC). PDAC itself is unique because of its pronounced tumor microenvironment that influences tumor progression, behavior and therapeutic resistance. Here we investigated, in patient-derived tumor xenograft (PDTX) models developed from fine needle biopsies, the cancer cells behavior, Epithelial-to-Mesenchymal Transition (EMT) and drug response. For this, we ...

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract and localize mainly in the stomach or small intestine. The metabolomic signatures of GISTs driven by different KIT gene mutations remain undiscovered and unexplored. The main aim of this pilot study was to determine and compare metabolomic profiles in GIST xenograft models with different genetic backgrounds. Metabolomic profiling ...

Patient-derived xenografts (PDXs) are resected human tumors engrafted into mice for preclinical studies and therapeutic testing. It has been proposed that the mouse host affects tumor evolution during PDX engraftment and propagation, affecting the accuracy of PDX modeling of human cancer. Here, we exhaustively analyze copy number alterations (CNAs) in 1,451 PDX and matched patient tumor (PT) samples from 509 PDX models. CNA inferences based on ...

Patient-derived xenografts (PDXs) have emerged as an important platform to elucidate new treatments and biomarkers in oncology. PDX models are used to address clinically relevant questions, including the contribution of tumour heterogeneity to therapeutic responsiveness, the patterns of cancer evolutionary dynamics during tumour progression and under drug pressure, and the mechanisms of resistance to treatment. The ability of PDX models to ...

Background and study aim: Typically, pancreatic patient-derived tumor xenografts (PDXs) are established by transplanting large tumor biopsies obtained through invasive surgery approaches into immunocompromised mice. We aimed to develop pancreatic PDXs by transplanting tumor tissue acquired by endoscopic ultrasound (EUS)-guided fine needle biopsies (FNB), assess take rates compared to surgery-derived PDXs, and demonstrate the histological and ...

Objective. Uterine sarcomas (US) and carcinosarcomas (CS) are rare, aggressive cancers. The lack of reliable preclinical models hampers the search for new treatment strategies and predictive biomarkers. To this end, we established and characterized US and CS patient-derived xenograft (PDX) models. Methods. Tumor fragments of US and CS were subcutaneously implanted into immunocompromised mice. Engrafted xenograft and original tumors were compared ...