المؤلفون: Todeschini, Letizia¹ (AUTHOR), Cristin, Luca¹ (AUTHOR), Martinino, Alessandro² (AUTHOR), Mattia, Amelia³ (AUTHOR), Agnes, Salvatore³ (AUTHOR), Giovinazzo, Francesco³ (AUTHOR) francesco.giovinazzo@policlinicogemelli.it

المصدر: Current Oncology. Jun2023, Vol. 30 Issue 6, p5574-5592. 19p. 1 Diagram, 2 Charts.

مصطلحات موضوعية: *MTOR inhibitors, *LIVER transplantation, *HEPATOCELLULAR carcinoma, *GRAFT rejection, *THERAPEUTICS

مستخلص: Liver transplantation is a treatment option for nonresectable patients with early-stage HCC, with more significant advantages when Milan criteria are fulfilled. An immunosuppressive regimen is required to reduce the risk of graft rejection after transplantation, and CNIs represent the drugs of choice in this setting. However, their inhibitory effect on T-cell activity accounts for a higher risk of tumour regrowth. mTOR inhibitors (mTORi) have been introduced as an alternative immunosuppressive approach to conventional CNI-based regimens to address both immunosuppression and cancer control. The PI3K-AKT-mTOR signalling pathway regulates protein translation, cell growth, and metabolism, and the pathway is frequently deregulated in human tumours. Several studies have suggested the role of mTORi in reducing HCC progression after LT, accounting for a lower recurrence rate. Furthermore, mTOR immunosuppression controls the renal damage associated with CNI exposure. Conversion to mTOR inhibitors is associated with stabilizing and recovering renal dysfunction, suggesting an essential renoprotective effect. Limitations in this therapeutic approach are related to their negative impact on lipid and glucose metabolism as well as on proteinuria development and wound healing. This review aims to summarize the roles of mTORi in managing patients with HCC undergoing LT. Strategies to overcome common adverse effects are also proposed. [ABSTRACT FROM AUTHOR]

المؤلفون: Letizia Todeschini, Luca Cristin, Alessandro Martinino, Amelia Mattia, Salvatore Agnes, Francesco Giovinazzo

المصدر: Current Oncology, Vol 30, Iss 6, Pp 5574-5592 (2023)

مصطلحات موضوعية: hepatocellular carcinoma, HCC, immunosuppression, liver transplantation, mTOR, mTOR inhibitors, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Liver transplantation is a treatment option for nonresectable patients with early-stage HCC, with more significant advantages when Milan criteria are fulfilled. An immunosuppressive regimen is required to reduce the risk of graft rejection after transplantation, and CNIs represent the drugs of choice in this setting. However, their inhibitory effect on T-cell activity accounts for a higher risk of tumour regrowth. mTOR inhibitors (mTORi) have been introduced as an alternative immunosuppressive approach to conventional CNI-based regimens to address both immunosuppression and cancer control. The PI3K-AKT-mTOR signalling pathway regulates protein translation, cell growth, and metabolism, and the pathway is frequently deregulated in human tumours. Several studies have suggested the role of mTORi in reducing HCC progression after LT, accounting for a lower recurrence rate. Furthermore, mTOR immunosuppression controls the renal damage associated with CNI exposure. Conversion to mTOR inhibitors is associated with stabilizing and recovering renal dysfunction, suggesting an essential renoprotective effect. Limitations in this therapeutic approach are related to their negative impact on lipid and glucose metabolism as well as on proteinuria development and wound healing. This review aims to summarize the roles of mTORi in managing patients with HCC undergoing LT. Strategies to overcome common adverse effects are also proposed.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1718-7729/30/6/421Test; https://doaj.org/toc/1198-0052Test; https://doaj.org/toc/1718-7729Test

الوصول الحر: https://doaj.org/article/97062eda1c124addbf7f2eb1e0cc5eb2Test

المؤلفون: Long, Yi-Xiu, Sun, Yue, Liu, Rui-Zhi, Zhang, Ming-Yi, Zhao, Jing, Wang, Yu-Qing, Zhou, Yu-Wen, Cheng, Ke, Chen, Ye, Zhu, Cai-Rong, Liu, Ji-Yan

المصدر: Current Oncology; Feb2022, Vol. 29 Issue 1, p267-282, 16p, 1 Diagram, 5 Charts, 3 Graphs

مصطلحات موضوعية: RANDOMIZED controlled trials, PNEUMONIA, CANCER chemotherapy, MTOR inhibitors, COMBINATION drug therapy, PROGRAMMED cell death 1 receptors, PNEUMONIA prevention, THERAPEUTIC use of antineoplastic agents, ONLINE information services, META-analysis, CONFIDENCE intervals, MEDICAL information storage & retrieval systems, MEDICAL databases, INFORMATION storage & retrieval systems, SYSTEMATIC reviews, TREATMENT effectiveness, IMMUNOLOGIC diseases, MEMBRANE proteins, IMMUNOSUPPRESSIVE agents, ODDS ratio, MEDLINE, CHEMICAL inhibitors

مستخلص: Purpose: Immune-related pneumonitis (IRP) has attracted extensive attention, owing to its increased mortality rate. Conventional chemotherapy (C) has been considered as an immunosuppressive agent and may thus reduce IRP's risk when used in combination with PD-1/L1 inhibitors. This study aimed to assess the risk of IRP with PD-1/L1 inhibitors plus chemotherapy (I+C) versus PD-1/L1 inhibitors alone (I) in solid cancer treatment. Method: Multiple databases were searched for RCTs before January 2021. This NMA was performed among I+C, I, and C to investigate IRP's risk. Subgroup analysis was carried out on the basis of different PD-1/L1 inhibitors and cancer types. Results: Thirty-one RCTs (19,624 patients) were included. The I+C group exhibited a lower risk of IRP in any grade (RR, 0.60; 95% CI, 0.38–0.95) and in grade 3–5 (RR, 0.44; 95% CI, 0.21–0.92) as opposed to the I group. The risk of any grade IRP with PD-1 plus chemotherapy was lower than that with PD-1 monotherapy (RR, 0.50; 95% CI, 0.28–0.89), although grade 3–5 IRP was similar. There was no statistically meaningful difference in the risk of any grade IRP between PD-L1 plus chemotherapy and PD-L1 inhibitors monotherapy (RR, 0.95; 95% CI, 0.43–2.09) or grade 3–5 IRP (RR, 0.71;95% CI, 0.24–2.07). In addition, compared with the I group, the I+C group was correlated with a decreased risk in IRP regardless of cancer type, while a substantial difference was only observed in NSCLC patients for grade 3–5 IRP (RR, 0.39; 95% CI, 0.15–0.98). Conclusion: In comparison to PD-1/L1 inhibitor treatment alone, combining chemotherapy with PD-1/L1 inhibitors might reduce the risk of IRP in the general population. Furthermore, PD-1 inhibitors in combination with chemotherapy were correlated with a decreased risk of IRP compared to PD-1 inhibitor treatment alone. In contrast to the I group, the I+C group exhibited a lower risk of IRP, especially for NSCLC patients. [ABSTRACT FROM AUTHOR]

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