Liver cancer is an aggressive tumor originating in the liver with a dismal prognosis. Current evidence suggests that liver cancer is the fifth most prevalent cancer worldwide and the second most deadly type of malignancy. Tumor heterogeneity accounts for the differences in drug responses among patients, emphasizing the importance of precision medicine. Patient-derived models of cancer are widely used preclinical models to study precision medicine since they preserve tumor heterogeneity ex vivo in the study of many cancers. Patient-derived models preserving cell-cell and cell-matrix interactions better recapitulate in vivo conditions, including patient-derived xenografts (PDXs), induced pluripotent stem cells (iPSCs), precision-cut liver slices (PCLSs), patient-derived organoids (PDOs), and patient-derived tumor spheroids (PDTSs). In this review, we provide a comprehensive overview of the different modalities used to establish preclinical models for precision medicine in liver cancer.
Pancreatic cancer (PC) is a fatal disease with a high mortality rate due to difficulties in early diagnosis and metastasis. Common sites of metastasis from PC include the liver, lung, stomach and kidney. Patients diagnosed at already the metastatic stages on presentation constitute 50-55% of the cases, with a 5-year survival rate of 3%. By contrast, secondary ovarian metastases account for 10-25% of all ovarian malignancies, though an accurate diagnosis remain challenging. The present study reports the rare case of a 42-year-old woman with primary hepatic metastasis and secondary ovarian metastasis from PC treated with two lines of immunotherapy, who is also experiencing severe treatment-associated toxicity. The patient first received combined immunotherapy consisting of camrelizumab (200 mg; day 1; every 3 weeks) and chemotherapy with nab-paclitaxel (125 mg/m 2 ; days 1 and 8; every 3 weeks) and gemcitabine (1,000 mg/m 2 ; days 1 and 8; every 3 weeks). She then exhibited a partial response following 4 months of treatment. However, 9 months after the initial treatment, the disease progressed with ovarian involvement, which was confirmed by surgery. Second-line treatment included immunotherapy, targeted therapy and oral chemotherapy (200 mg sintilimab on day 1; 50 mg tegafur from days 1-14, twice daily; and 8 mg anlotinib from days 1-14, every 3 weeks). The progression-free survival time from this second-line treatment was 6 months.Immunotherapy was permanently aborted due to severe intestinal inflammation, where four lines of combined treatments were recommended. The patient remains on treatment with a good quality of life in July 2022, and a current overall survival time of >24 months. In conclusion, the diagnosis of metastatic PC leads to a poor prognosis, but ovarian metastasis from PC is rare. Furthermore, the combination of immunotherapy with chemotherapy or antiangiogenic inhibitors shows promise as a treatment strategy for advanced stages of PC.
To investigate the role of patient-derived organoid (PDO) model in the precision medicine of advanced clear cell renal cell carcinoma (ccRCC), we retrospectively analyzed the clinical data of seven cases of ccRCC diagnosed by operation and pathology in Renji Hospital from September 2021 to September 2022. The seven patients were diagnosed with advanced ccRCC with or without remote metastasis. Cytoreductive and radical nephrectomy was performed respectively. To predict the response to immunotherapy and provide personalized medicine recommendation, a PDO model based on air-liquid interface system was established from the surgical resected tumor and subsequent drug screening was performed. Hematoxylin and eosin (H&E) staining and immunohistochemistry revealed that the PDO recapitulated the histological feature of parent tumor. Immunofluorescence staining identified that CD3+ T cells, SMA+ cancer associated fibroblasts, and CD31+ endothelial cells were preserved in PDO models. Fluorescence activated cell sorter (FACS) revealed an evidently increased ratio of CD8+/CD4+ T cells and apoptotic tumor cells in PDO treated with toripalimab than those treated with IgG4. The results showed that toripalimab is able to rescue the excessive death of CD8+ T cells by critically reversing the immune exhaustion state of ccRCC in PDO model. This research validated that PDO is a promising and faithful preclinical model for prediction of immunotherapy response in patients with ccRCC.
Editorial on the Research Topic Perioperative management and cancer outcomePerioperative management plays a critical role in determining the outcomes of patients with cancer undergoing surgery. It encompasses a comprehensive approach that involves careful planning, meticulous execution, and attentive postoperative care. The perioperative period, which includes the preoperative, intraoperative, and postoperative phases, presents numerous challenges and opportunities to optimize patient care and improve treatment outcomes. The Research Topic aimed to present some of the more recent evidence integrating clinical observations and experimental findings linking perioperative management and cancer-related outcomes.Several studies focused on the potential long-term effects of perioperative and intraoperative pharmacological management on tumors. The influence of anesthetic approaches on cancer patients is complex. Abundant evidence from animal studies has suggested that different types of anesthetics can influence tumor progression and survival outcomes in patients with malignancies (1, 2). The impact of intraoperative low-dose dopamine administration in hepatic surgery emerges as another intriguing topic within this Research Topic. The propensity score matching analysis examining its association with survival rates in hepatocellular carcinoma patients conducted by Wang et al. highlight the potential implications of such intervention on long-term outcomes. Dexmedetomidine is a frequently used sedative during surgery. Xu et al. conducted a meta-analysis and showed the impact of dexmedetomidine in reducing systemic inflammation and postoperative cognitive dysfunction and improving recovery in patients undergoing digestive tract cancer surgery.Importantly, the Research Topic also addresses the value of non-surgical interventions in perioperative care. Prehabilitation is a proposed modality for optimizing preoperative conditions to improve postoperative outcomes. Studies reported potential advantages for various surgical procedures (3, 4). However, according to Zhang X. et al.'s systematic reviews and meta-analyses, rehabilitation did not significantly enhance postoperative
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