Project description:Synthetic lethal siRNA screen using a kinome library containing 939 druggable genes in the TN-IBC cell line SUM149PT, in combination with EPA treatment.
Project description:To identify possible novel targets for the treatment of plexiform neurofibroma formation through a synthetic lethal shRNA library screen in the tumorigenic cell of origin, Schwann cells.
Project description:Using a kinome-centred CRISPR/Cas9 genetic screen, we identify here that inhibition of the epidermal growth factor receptor (EGFR) is synthetic lethal with lenvatinib in liver cancer cells. We found that the combination of the EGFR inhibitor gefitinib and lenvatinib displays potent anti-proliferative effect in HCC cell lines that express EGFR in vitro and of xenografted HCC cell lines or patient-derived HCC tumours in mice. Herre, we analyzed the different transcriptome profiling of HCC cells treated with DMSO, lenvatinib, gefitinib, and lenvatinib plus gefitinib by RNA-sequencing.
Project description:We collected matched pretreatment blood and tumor samples from 19 patients with primary TN-IBC enrolled in a phase II clinical trial (NCT02876107). Patients were treated with neoadjuvant chemotherapy (NAC) or the anti-EGFR antibody panitumumab (PmAb) plus NAC (PmAb/NAC). We conducted whole-exome sequencing, RNA sequencing, and CIBERSORT analyses for these TN-IBC samples and compare the genetic and molecular profiles with similarly analyzed stage III TN-non-IBC patient samples. We also compared the genetic and molecular characteristics of TN-IBC in patients who had a pathologic complete response (pCR) to NAC or PmAb/NAC treatment, a suitable surrogate endpoint for IBC, with those who did not have pCR (non-pCR).
Project description:This is data for the evaluation of a new way of counting sgRNAs in CRISPR screens using padlock probes and UMIs. It is compared to the typical PCR-based approach. In particular, a dropout screen was performed in MiaPaCa-2 cells using the Human Kinome CRISPR pooled library (Addgene #75314)
Project description:sgRNA whole genome library sequencing in OCI-AML5-Cas9 EKO library cells overexpressing HMGA-YFP or control YFP vectors. The goal of this experiment is to identify synthetic lethal and synthetic rescue sgRNAs with regard to HMGA2 overexpression in AML.
Project description:The MYC oncogene is often dysregulated in human cancer, including hepatocellular carcinoma (HCC). However, MYC is considered undruggable to date. Here, we comprehensively identify genes essential for the survival of MYC-high but not MYC-low cells by performing a CRISPR/Cas9 genome-wide screen in a MYC-conditional HCC model. Our screen identifies novel MYC-synthetic lethal interactions, as well as most previously identified MYC-synthetic lethal genes. In particular, we found genes involved in nuclear to cytoplasmic transport to be MYC-synthetic lethal in HCC, and we show that many of these genes are transcriptionally upregulated in MYC-high murine HCC.
