Project description:Nectin-4 is a new therapeutic target in various carcinomas. We were interested in resistance to anti-nectin 4 ADC in breast cancer and the way to overcome it. Tumor RNAs were extracted from sensitive and resistant pre-clinical models. RNA-Seq libraries were created using Truseq RNA-Seq Library kit.
Project description:Nectin-4 is a new therapeutic target in various carcinomas. We were interested in resistance to anti-nectin 4 ADC in breast cancer and the way to overcome it. Tumor DNA were extracted from sensitive and resistant pre-clinical models. Genomic profiles of samples were established by using array-CGH onto 4×180K CGH microarrays.
Project description:A phase II clinical study of RC48-ADC combined with Bevacizumab as late-line treatment in patients with HER2-expressed metastatic colorectal cancer. A total of 30 patients are planned to be enrolled.
Project description:We performed lung ADC and SCC transcriptome profiling from KRasG12D; Fbw7f/f murine lung tumors by RNA-seq and compared them with a consensus lung SCC signature using data from two different SCC models (Lkb1f/f; Ptenf/f, Cancer Cell 2014 and LSL-Sox2; Ptenf/f; Cdkn2abf/f, Cancer Cell 2016) that has been validated in human lung SCC
Project description:Androgen receptor positive prostate cancer (PC), castration resistant prostate cancer (CRPC) and neuroendocrine prostate cancer (NEPC) represent a spectrum of malignancies that invariably become resistant to treatment with targeted and cytotoxic agents. There is no known common pathway responsible for these pleotropic mechanisms of resistance. The MUC1 gene is aberrantly expressed in CRPC and NEPC in association with poor clinical outcomes. The present results demonstrate that the oncogenic MUC1-C protein is necessary for resistance of (i) PC cells to enzalutamide (ENZ), and (ii) CRPC and NEPC cells to docetaxel (DTX). We show that MUC1-C-mediated ENZ and DTX resistance is conferred by upregulation of aerobic glycolysis and suppression of reactive oxygen species (ROS) necessary for self-renewal capacity. Common dependence of these drug-resistant phenotypes on MUC1-C for the cancer stem cell (CSC) state thus identified a potential new target for their treatment. cIn this context, we further demonstrate that targeting MUC1-C with an antibody-drug conjugate (ADC) is highly effective in suppressing (i) self-renewal of drug-resistant CRPC and NEPC CSCs and (ii) growth of t-NEPC tumor xenografts derived from drug-resistant cells and a patient with refractory disease. These findings reveal a shared MUC1-C-dependent pathway in drug-resistant CRPC and NEPC progression and identify MUC1-C as a target for their treatment with an ADC.
