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Establishing an applicable preclinical model is vital for translational cancer research. Patient-derived xenograft has been important preclinical model systems and widely used for cancer research. Patient-derived xenograft models that represent the tumors of the patients are necessary to better translate research discoveries and to test potential therapeutic approaches. However, research in this field is hampered by the limited engraftment rate. In this review, we go over a large number of researches on patient-derived xenograft transplantation and firstly systematically summarize the main factors in methodology to successfully establish models. These results will be applied to the development of patient-derived xenograft leading to better preclinical research.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738839 | PMC |
http://dx.doi.org/10.7150/jca.51749 | DOI Listing |
Signal Transduct Target Ther
September 2025
State Key Laboratory of Molecular Oncology & Department of Medical Oncology & Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Small-cell lung cancer (SCLC), an aggressive neuroendocrine tumor strongly associated with exposure to tobacco carcinogens, is characterized by early dissemination and dismal prognosis with a five-year overall survival of less than 7%. High-frequency gain-of-function mutations in oncogenes are rarely reported, and intratumor heterogeneity (ITH) remains to be determined in SCLC. Here, via multiomics analyses of 314 SCLCs, we found that the ASCL1/MKI67 and ASCL1/CRIP2 clusters accounted for 74.
View Article and Find Full Text PDFJ Clin Invest
September 2025
State Key Laboratory of Molecular Oncology, National Cancer Center/National, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Pancreatic cancer (PC) is notoriously resistant to both chemotherapy and immunotherapy, presenting a major therapeutic challenge. Epigenetic modifications play a critical role in PC progression, yet their contribution to chemoimmunotherapy resistance remains poorly understood. Here, we identified the transcription factor ZEB1 as a critical driver of chemoimmunotherapy resistance in PC.
View Article and Find Full Text PDFJ Proteome Res
September 2025
State Key Laboratory of Medical Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Research Unit of Proteomics & Research and Development of New Drug of Chinese Academy of Medical Sciences, Institute of Lifeomics, Beijing 102206, China.
Hepatocellular carcinoma (HCC) constitutes approximately 90% of liver cancers, yet its early detection remains challenging due to the low sensitivity of current diagnostic methods and the difficulty in identifying minimal cancer cells within the body. This study employed a patient-derived xenograft (PDX) mouse model to screen for biomarkers, leveraging its advantage of low background interference compared to human serum exosome studies. Using a novel microextraction technique, exosomes were isolated from just one microliter of serum from HCC PDX mice, followed by proteomic profiling.
View Article and Find Full Text PDFJ Med Chem
September 2025
Applied Pharmaceutical Science, Inc., Building 10-1, No.2, Jingyuan North Street, BDA, Beijing 100176, China.
This study reports the discovery and preclinical activity of APS03118, a novel selective RET inhibitor featuring a novel tricyclic pyrazolo[3',4':3,4]pyrazolo[1,5-]pyridine hinge-binding scaffold designed to overcome acquired resistance to first-generation selective RET inhibitors (SRIs). By enhancing hydrogen bonding with conserved hinge residues (Glu805, Ala807), APS03118 potently inhibits wild-type RET and diverse resistance mutations, including solvent-front (G810R/S/C), gatekeeper (V804M/L/E), roof (L730I/M), and hinge (Y806C/N/H) variants. In preclinical models, APS03118 induced complete tumor regression in KIF5B-RET and CCDC6-RET V804 M patient-derived xenografts (PDXs) and significantly prolonged survival in an intracranial CCDC6-RET metastasis model.
View Article and Find Full Text PDFJ Med Chem
September 2025
Repare Therapeutics, 7171 Frederick-Banting, Building 2, H4S 1Z9 Montréal, Québec, Canada.
DNA polymerase theta (Polθ) plays a critical role in repairing DNA double-strand breaks through microhomology-mediated end joining (MMEJ) and has emerged as a key synthetic lethal drug target in cancers with homologous recombination (HR) deficiencies. Its inhibition has shown a strong potential to synergize with PARP inhibitors, particularly in tumors with deleterious or mutations. Here, we describe the discovery and preclinical development of RP-2119, a selective, potent, and bioavailable Polθ ATPase inhibitor.
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