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Establishment of appropriate preclinical research models is important for the tumor transformation research. Although the development of new anti-tumor drugs is emergent, but most of drugs are failed in phaseⅡ clinical trials due to the limitations of preclinical research models. Patient-derived tumor xenograft (PDX) isone of the novel tumor research models established by inoculating patient tumors tissue directly into immunodeficient mice. PDX is a preclinical research model with high clinical predictive value due to its high conservatismof histological and genetic characteristics with donor tumors. Generally, PDX models are widely used in preclinical drug evaluation, biomarker identification and personalized medical treatment. In this review, the methods ofPDX model establishment, the advantages, the applications and the limitations of PDX model in tumor clinical research are summarized. At last, we prospect the future development of PDX model in tumor related research.

Pancreatic cancer (PC) is a highly aggressive and deadly malignancy with limited treatment options and poor prognosis. Identifying new therapeutic targets and developing effective strategies for PC treatment is of utmost importance. Here, we revealed that SHCBP1 is significantly overexpressed in PC and negatively correlated with patient prognosis. Knockout of SHCBP1 inhibits the proliferation and migration of PC cells in vitro, and suppresses the tumor growth in vivo. In addition, we identified AZD5582 as a novel inhibitor of SHCBP1, which efficiently restrains the growth of PC in cell lines, organoids, and patient‐derived xenografts. Mechanistically, we found that AZD5582 induced the apoptosis of PC cells by inhibiting the activity of PI3K/AKT signaling and preventing the degradation of TP53. Collectively, our study highlights SHCBP1 as a potential therapeutic target and its inhibitor AZD5582 as a viable agent for PC treatment strategies. [ABSTRACT FROM AUTHOR]

Primary cilia detect and transmit environmental signals into cells. Primary cilia are absent in a subset of ductal carcinomas characterized by distinctive biological activities, and recovery of cilia with normal functionality has been shown to have therapeutic potential in some cancer types. Therefore, elucidation of the underlying mechanism and clinical significance of ciliary loss in ductal carcinomas could help develop effective treatment strategies. Here, we identified a link between Shc1-binding protein (SHCBP1) and cilia in ductal carcinomas. Shcbp1 knockout in transgenic mice profoundly impeded tumor progression and metastasis, prolonging survival. Single-cell transcriptome analysis revealed a functional connection between SHCBP1 deficiency and increased tumor ciliogenesis. SHCBP1 ablation restored ciliogenesis in unciliated ductal carcinoma by promoting the proximity between the midbody remnant (MBR) and centrosome through enhanced Rab8 GTPase activity and Rab8GTP positioning within the MBR. Inhibition of tumor progression by SHCBP1 loss relied on the recovery of ciliogenesis. Analysis of a large cohort of patients with ductal carcinoma revealed a negative correlation between SHCBP1-induced ciliary loss and patient prognosis. Restoring ciliogenesis via SHCBP1 ablation elicited therapeutic effects in patient-derived xenograft models. Together, this study delineates that induction of MBR-centrosome proximity through SHCBP1-deficiency reactivates ciliogenesis, offering unique opportunities for the treatment of unciliated ductal carcinomas. Significance: SHCBP1 depletion rescues tumor ciliogenesis by enhancing Rab8 GTPase activity to restore the proximity of the  midbody remnant to the centrosome, which impedes progression of ductal carcinomas and suggests potential therapeutic strategies., (©2024 American Association for Cancer Research.)