Genentech Inc., is a biotechnology corporation which became a subsidiary of Roche in 2009. Genentech Research and Early Development operates as an independent center within Roche.As of August 2013, Genentech employed more than 12,300 people. In July 2014, Genentech announced its acquisition of Seragon for up to $1.725 billion. Wikipedia.
Genentech and Xenon Pharmaceuticals Inc. | Date: 2016-09-23
The invention provides compounds having the general formula I: and pharmaceutically acceptable salts thereof, wherein the variablesR^(A), R^(AA), subscipt n, ring A, X^(2), L, subscript m, X^(1), R^(1), R^(2), R^(3), R^(4), R^(5), and R^(N )have the meaning as described herein, and compositions containing such compounds and methods for using such compounds and compositions.
Genentech | Date: 2016-08-15
Provided herein are biomarkers, and combinations of biomarkers, for predicting sensitivity to cancer treatments.
EMBO Journal | Year: 2012
Aberrant regulation of the Wnt signalling pathway has emerged as a prevalent theme in cancer biology. This chapter summarizes the research that provides a proof of concept for inhibiting Wnt signalling in cancer, the potential means by which this could be achieved, and some recent advances towards this goal. A brief discussion of molecular diagnostics and possible safety concerns is also provided. © 2012 European Molecular Biology Organization.
Science translational medicine | Year: 2012
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common cause of familial Parkinson's disease (PD). Although biochemical studies have shown that certain PD mutations confer elevated kinase activity in vitro on LRRK2, there are no methods available to directly monitor LRRK2 kinase activity in vivo. We demonstrate that LRRK2 autophosphorylation on Ser(1292) occurs in vivo and is enhanced by several familial PD mutations including N1437H, R1441G/C, G2019S, and I2020T. Combining two PD mutations together further increases Ser(1292) autophosphorylation. Mutation of Ser(1292) to alanine (S1292A) ameliorates the effects of LRRK2 PD mutations on neurite outgrowth in cultured rat embryonic primary neurons. Using cell-based and pharmacodynamic assays with phosphorylated Ser(1292) as the readout, we developed a brain-penetrating LRRK2 kinase inhibitor that blocks Ser(1292) autophosphorylation in vivo and attenuates the cellular consequences of LRRK2 PD mutations in vitro. These data suggest that Ser(1292) autophosphorylation may be a useful indicator of LRRK2 kinase activity in vivo and may contribute to the cellular effects of certain PD mutations.
Cold Spring Harbor Perspectives in Biology | Year: 2012
Aberrant regulation of the Wnt signaling pathway is a prevalent theme in cancer biology. From the earliest observation that Wnt overexpression could lead to malignant transformation of mouse mammary tissue to the most recent genetic discoveries gleaned from tumor genome sequencing, the Wnt pathway continues to evolve as a central mechanism in cancer biology. This article summarizes the evidence supporting a role for Wnt signaling in human cancer. This includes a review of the genetic mutations affecting Wnt pathway components, as well as some of epigenetic mechanisms that alter expression of genes relevant to Wnt. I also highlight some research on the cooperativity of Wnt with other signaling pathways in cancer. Finally, some emphasis is placed on laboratory research that provides a proof of concept for the therapeutic inhibition of Wnt signaling in cancer. © 2012 Cold Spring Harbor Laboratory Press; all rights reserved.
Nature Genetics | Year: 2013
Our understanding of inherited risk factors for colorectal cancer (CRC) is incomplete. A new study reports the identification of germline CRC risk variants that adversely affect the proofreading function of DNA polymerases encoded by POLE and POLD1. © 2013 Nature America, Inc. All rights reserved.
Nature genetics | Year: 2010
To understand the genetic predisposition to selective immunoglobulin A deficiency (IgAD), we performed a genome-wide association study in 430 affected individuals (cases) from Sweden and Iceland and 1,090 ethnically matched controls, and we performed replication studies in two independent European cohorts. In addition to the known association of HLA with IgAD, we identified association with a nonsynonymous variant in IFIH1 (rs1990760G>A, P = 7.3 x 10(-10)) which was previously associated with type 1 diabetes and systemic lupus erythematosus. Variants in CLEC16A, another known autoimmunity locus, showed suggestive evidence for association (rs6498142C>G, P = 1.8 x 10(-7)), and 29 additional loci were identified with P < 5 x 10(-5). A survey in IgAD of 118 validated non-HLA autoimmunity loci indicated a significant enrichment for association with autoimmunity loci as compared to non-autoimmunity loci (P = 9.0 x 10(-4)) or random SNPs across the genome (P < 0.0001). These findings support the hypothesis that autoimmune mechanisms may contribute to the pathogenesis of IgAD.
Science Translational Medicine | Year: 2012
Amplification of the ERBB2 gene, which encodes human epidermal growth factor receptor 2 (HER2), causes the overexpression of a major proliferative driver for a subset of breast and gastric cancers. Treatments for patients with HER2-positive cancer include the monoclonal antibody trastuzumab and, in the case of metastatic breast cancer, the tyrosine kinase inhibitor lapatinib. Despite significant improvement in patient outcome as a result of these therapies, challenges remain. This Review focuses on proposed mechanisms of action and resistance in the context of potential new therapeutic options. Therapeutic approaches currently in development likely will yield additional clinically meaningful improvements for patients with HER2-positive cancer.
Nature Genetics | Year: 2012
A new exome sequencing study of individuals with hepatocellular carcinoma (HCC) reveals imprints of mutagenic exposure and identifies new genes contributing to tumorigenesis. This work joins several recent publications reporting whole-genome, exome and RNA sequencing in HCC, which together provide a comprehensive genomic landscape and new insights into the etiology of liver cancer. © 2012 Nature America, Inc. All rights reserved.
Nature Genetics | Year: 2011
A new study shows that the PTPN22 coding variant associated with autoimmunity is a loss-of-function allele that causes the protein tyrosine phosphatase encoded by PTPN22 to undergo accelerated degradation, resulting in enhanced signaling in several immune cell types. © 2011 Nature America, Inc. All rights reserved.