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Cancer cell killing by target antigen engagement with engineered complementary intracellular antibody single domains fused to pro-caspase3.
(NATURE PORTFOLIO, 2019-06-12)
Many tumour causing proteins, such as those expressed after chromosomal translocations or from point mutations, are intracellular and are not enzymes per se amenable to conventional drug targeting. We previously demonstrated ...
Identification of 19 new risk loci and potential regulatory mechanisms influencing susceptibility to testicular germ cell tumor.
(NATURE PUBLISHING GROUP, 2017-07-01)
Genome-wide association studies (GWAS) have transformed understanding of susceptibility to testicular germ cell tumors (TGCTs), but much of the heritability remains unexplained. Here we report a new GWAS, a meta-analysis ...
Fragment-based screening identifies molecules targeting the substrate-binding ankyrin repeat domains of tankyrase.
(NATURE PORTFOLIO, 2019-12-13)
The PARP enzyme and scaffolding protein tankyrase (TNKS, TNKS2) uses its ankyrin repeat clusters (ARCs) to bind a wide range of proteins and thereby controls diverse cellular functions. A number of these are implicated in ...
Solution structure of the Hop TPR2A domain and investigation of target druggability by NMR, biochemical and in silico approaches.
(NATURE PORTFOLIO, 2020-09-29)
Heat shock protein 90 (Hsp90) is a molecular chaperone that plays an important role in tumour biology by promoting the stabilisation and activity of oncogenic 'client' proteins. Inhibition of Hsp90 by small-molecule drugs, ...
Surfaceome interrogation using an RNA-seq approach highlights leukemia initiating cell biomarkers in an LMO2 T cell transgenic model.
(NATURE PORTFOLIO, 2019-04-08)
The surfaceome is critical because surface proteins provide a gateway for internal signals and transfer of molecules into cells, and surfaceome differences can influence therapy response. We have used a surfaceome analysis ...
Selective protection of human cardiomyocytes from anthracycline cardiotoxicity by small molecule inhibitors of MAP4K4.
(NATURE PORTFOLIO, 2020-07-21)
Given the poor track record to date of animal models for creating cardioprotective drugs, human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have been proposed as a therapeutically relevant human platform to ...
The kinase polypharmacology landscape of clinical PARP inhibitors.
(NATURE PORTFOLIO, 2020-02-17)
Polypharmacology plays an important role in defining response and adverse effects of drugs. For some mechanisms, experimentally mapping polypharmacology is commonplace, although this is typically done within the same protein ...
Circulating Cell-Free DNA to Guide Prostate Cancer Treatment with PARP Inhibition.
(AMER ASSOC CANCER RESEARCH, 2017-09-01)
Biomarkers for more precise patient care are needed in metastatic prostate cancer. We have reported a phase II trial (TOPARP-A) of the PARP inhibitor olaparib in metastatic prostate cancer, demonstrating antitumor activity ...
Function of Human Tumor-Infiltrating Lymphocytes in Early-Stage Non-Small Cell Lung Cancer.
(AMER ASSOC CANCER RESEARCH, 2019-06-01)
Cancer progression is marked by dysfunctional tumor-infiltrating lymphocytes (TIL) with high inhibitory receptor (IR) expression. Because IR blockade has led to clinical responses in some patients with non-small cell lung ...
A preclinical model to investigate the role of surgically-induced inflammation in tumor responses to intraoperative photodynamic therapy.
(WILEY, 2018-07-01)
OBJECTIVE: Inflammation is a well-known consequence of surgery. Although surgical debulking of tumor is beneficial to patients, the onset of inflammation in injured tissue may impede the success of adjuvant therapies. One ...