Cannonandrews0841

Introduction Combination of trastuzumab (T) and lapatinib (L) has been showed to significantly improve the prognosis of HER2+ heavily pretreated metastatic breast cancer (MBC). Whether TL combined chemotherapy (TLC) can further improve the efficacy in HER2+ MBC remains to be further studied. The aim of the study was to report the first real-world data of TLC in HER2+ MBC, including the efficacy, safety and treatment patterns. Methods Patients with HER2+ MBC treated with TLC in 5 institutions of China from September 2013 to July 2019 were included. Progression free survival (PFS), objective response rate (ORR), overall survival (OS), toxicity profile and treatment pattern were reported. Results A total of 285 patients were included. click here 88.8% were exposed to trastuzumab and 49.2% received 2 or more lines of systematic therapy before TLC previously. The most common chemotherapy regimens combined with TL were capecitabine (40.7%) and vinorelbine (21.4%) and almost 1/3 received maintenance treatment after TLC. Medianed promising effects and tolerable safety in HER2+MBC, even in patients with BM, providing a theoretical basis for clinical practice. Clinical Trial Registration ClinicalTrials.gov, Identifier NCT04001634. Copyright © 2020 Li, Gong, Lu, Zhou, Luo, Li, Li, Ge, Xu and Wang.Development of multidrug resistance (MDR) still remains a major obstacle to the long-term success of cancer therapy. P-glycoprotein (P-gp) is a well-identified membrane transporter with capability to efflux drug molecules out of the cancer cell leading to reduced efficiency of chemotherapy. Cancer cells upregulate P-gp expression as an adaptive response to evade chemotherapy mediated cell death. While several P-gp inhibitors have been discovered by in silico and pre-clinical studies, very few have successfully passed all phases of the clinical trials. Studies show that application of P-gp inhibitors in cancer therapy regimen following development of MDR achieved limited beneficial outcomes. While, the non-specific substrate binding to P-gp has made the drug-design a challenge, a bigger perplexing challenge comes from its role in tumor immunology. Expression of P-gp was noted immune cell phenotypes with apparently antagonistic functionality. Both pro-tumor MΦ2-macrophages and, anti-tumor NK-cell and Th17/CD4+T cell subsets have shown enhanced expression of P-gp. While drug based inhibition of P-gp in pro-tumor immune cell phenotypes could promote tumor elimination, however, it would not be a rational choice to exert inhibition of P-gp on anti-tumor immune cell phenotypes. This mutually exclusive paradigm of P-gp functionality requires a more comprehensive and detailed understanding of its role in tumor microenvironment with active interplay of cancer and immune cells in the tumor mileu. In this review, we focus on the current understanding of the role of P-gp in cancer cells and immune cells and finally attempt to highlight some caveats in the current understanding of its role in comprehensive tumor microenvironment along with challenges in the development of P-gp inhibitors toward anti-cancer therapy. Copyright © 2020 Robinson and Tiriveedhi.Background The aim of this study was to identify more accurate variables to improve prognostication of individual patients with colorectal liver metastases (CRLM). Clinicopathological characteristics only partly explain the large range in survival rates. Methods MessengerRNA expression profiles of resected CRLM of two patient groups were analysed by mRNA sequencing poor survivors (death from recurrent disease 60 months after surgery). Tumour and adjacent liver parenchyma samples were analysed. Results MessengerRNA expression profiling of the tumour samples identified 77 genes that were differentially expressed between the two survival groups at a False Discovery Rate (FDR) less then 0.1. In the adjacent liver parenchyma samples only one gene, MTRNR2L1, showed significantly higher expression in the good survivors. Pathway analysis showed higher expression of immune-related and stroma-related genes in tumour samples from good survivors. Expression data was then validated by immunohistochemistry in two cohorts comprising a total of 125 patients. Immunohistochemical markers that showed to be associated with good survival in the total cohort were high K/L+ infiltration in tumour stroma [p = 0.029; OR 2.500 (95% CI 1.100-5.682)] and high CD79A+ infiltration in tumour stroma [p = 0.036; OR 2.428 (95%CI 1.062-5.552)]. Conclusions A high stromal infiltration of CD79A+ B cells and K/L+ plasma cells might be favourable prognostic biomarkers after surgery for CRLM. Copyright © 2020 Hof, Visser, Höppener, Nierop, Terpstra, Gouw, Grünhagen, Verhoef, Sijmons, de Jong and Kok.Background Neoadjuvant chemotherapy (NAC) has been of recent interest as an alternative to upfront surgery followed by adjuvant chemotherapy in patients with pancreatic ductal adenocarcinoma (PDAC). However, a subset of patients does not respond to NAC and may have been better managed by upfront surgery. Hence, there is an unmet need for accurate biomarkers for predicting NAC response in PDAC. We aimed to identify upregulated proteins in tumor tissue from poor- and good-NAC responders. Methods Tumor and adjacent pancreas tissue samples were obtained following surgical resection from NAC-treated PDAC patients. SWATH-MS proteomic analysis was performed to identify and quantify proteins in tissue samples. Statistical analysis was performed to identify biomarkers for NAC response. Pathway analysis was performed to characterize affected canonical pathways in good- and poor-NAC responders. Results A total of 3,156 proteins were identified, with 19 being were significantly upregulated in poor-responders compared to good-responders (log2 ratio > 2, p less then 0.05). Those with the greatest ability to predict poor-NAC response were GRP78, CADM1, PGES2, and RUXF. Notably, canonical pathways that were significantly upregulated in good-responders included acute phase signaling and macrophage activation, indicating a heightened immune response in these patients. Conclusion A novel biomarker signature for poor-NAC response in PDAC was identified. Copyright © 2020 Sahni, Nahm, Krisp, Molloy, Mehta, Maloney, Itchins, Pavlakis, Clarke, Chan, Gill, Howell, Samra and Mittal.