Browsing Clinical Studies by author "Workman, Paul"
Now showing items 1-18 of 18
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Challenges to curing primary brain tumours.
Aldape, K; Brindle, KM; Chesler, L; Chopra, R; Gajjar, A; et al. (NATURE PUBLISHING GROUP, 2019-08-01)Despite decades of research, brain tumours remain among the deadliest of all forms of cancer. The ability of these tumours to resist almost all conventional and novel treatments relates, in part, to the unique cell-intrinsic ... -
Critical parameters in targeted drug development: the pharmacological audit trail.
Banerji, U; Workman, P (W B SAUNDERS CO-ELSEVIER INC, 2016-08-01)The Pharmacological Audit Trail (PhAT) comprises a set of critical questions that need to be asked during discovery and development of an anticancer drug. Key aspects include: (1) defining a patient population; (2) ... -
Drug discovery in advanced prostate cancer: translating biology into therapy.
Yap, TA; Smith, AD; Ferraldeschi, R; Al-Lazikani, B; Workman, P; et al. (NATURE PUBLISHING GROUP, 2016-10-01)Castration-resistant prostate cancer (CRPC) is associated with a poor prognosis and poses considerable therapeutic challenges. Recent genetic and technological advances have provided insights into prostate cancer biology ... -
From patent to patient: analysing access to innovative cancer drugs.
Sharpe, E; Hoey, R; Yap, C; Workman, P (ELSEVIER SCI LTD, 2020-09-01)Analysis of cancer drugs licensed through the European Medicines Agency (EMA) in 2000-2016 shows that the number of authorisations increased over that timeframe. The median number of licensed drugs each year rose from six ... -
HER3 Is an Actionable Target in Advanced Prostate Cancer.
Gil, V; Miranda, S; Riisnaes, R; Gurel, B; D'Ambrosio, M; et al. (AMER ASSOC CANCER RESEARCH, 2021-12-15)It has been recognized for decades that ERBB signaling is important in prostate cancer, but targeting ERBB receptors as a therapeutic strategy for prostate cancer has been ineffective clinically. However, we show here that ... -
Inhibition of mTOR-kinase destabilizes MYCN and is a potential therapy for MYCN-dependent tumors.
Vaughan, L; Clarke, PA; Barker, K; Chanthery, Y; Gustafson, CW; et al. (IMPACT JOURNALS LLC, 2016-09-06)MYC oncoproteins deliver a potent oncogenic stimulus in several human cancers, making them major targets for drug development, but efforts to deliver clinically practical therapeutics have not yet been realized. In childhood ... -
MIR21 Drives Resistance to Heat Shock Protein 90 Inhibition in Cholangiocarcinoma.
Lampis, A; Carotenuto, P; Vlachogiannis, G; Cascione, L; Hedayat, S; et al. (W B SAUNDERS CO-ELSEVIER INC, 2018-03-01)BACKGROUND & AIMS: Cholangiocarcinomas (CCA) are resistant to chemotherapy, so new therapeutic agents are needed. We performed a screen to identify small-molecule compounds that are active against CCAs. Levels of microRNA ... -
Modulation of Biliary Cancer Chemo-Resistance Through MicroRNA-Mediated Rewiring of the Expansion of CD133+ Cells.
Carotenuto, P; Hedayat, S; Fassan, M; Cardinale, V; Lampis, A; et al. (LIPPINCOTT WILLIAMS & WILKINS, 2020-09-10)BACKGROUND AND AIMS: Changes in single microRNA (miRNA) expression have been associated with chemo-resistance in biliary tract cancers (BTCs). However, a global assessment of the dynamic role of the microRNome has never ... -
Modulation of pancreatic cancer cell sensitivity to FOLFIRINOX through microRNA-mediated regulation of DNA damage.
Carotenuto, P; Amato, F; Lampis, A; Rae, C; Hedayat, S; et al. (NATURE PORTFOLIO, 2021-11-18)FOLFIRINOX, a combination of chemotherapy drugs (Fluorouracil, Oxaliplatin, Irinotecan -FOI), provides the best clinical benefit in pancreatic ductal adenocarcinoma (PDAC) patients. In this study we explore the role of ... -
Modulation of Plasma Metabolite Biomarkers of the MAPK Pathway with MEK Inhibitor RO4987655: Pharmacodynamic and Predictive Potential in Metastatic Melanoma.
Ang, JE; Pal, A; Asad, YJ; Henley, AT; Valenti, M; et al. (AMER ASSOC CANCER RESEARCH, 2017-10-01)MAPK pathway activation is frequently observed in human malignancies, including melanoma, and is associated with sensitivity to MEK inhibition and changes in cellular metabolism. Using quantitative mass spectrometry-based ... -
Orally bioavailable CDK9/2 inhibitor shows mechanism-based therapeutic potential in MYCN-driven neuroblastoma.
Poon, E; Liang, T; Jamin, Y; Walz, S; Kwok, C; et al. (AMER SOC CLINICAL INVESTIGATION INC, 2020-11-02)The undruggable nature of oncogenic Myc transcription factors poses a therapeutic challenge in neuroblastoma, a pediatric cancer in which MYCN amplification is strongly associated with unfavorable outcome. Here, we show ... -
Patient-derived organoids model treatment response of metastatic gastrointestinal cancers.
Vlachogiannis, G; Hedayat, S; Vatsiou, A; Jamin, Y; Fernández-Mateos, J; et al. (AMER ASSOC ADVANCEMENT SCIENCE, 2018-02-23)Patient-derived organoids (PDOs) have recently emerged as robust preclinical models; however, their potential to predict clinical outcomes in patients has remained unclear. We report on a living biobank of PDOs from ... -
Pharmacodynamic and Clinical Results from a Phase I/II Study of the HSP90 Inhibitor Onalespib in Combination with Abiraterone Acetate in Prostate Cancer.
Slovin, S; Hussain, S; Saad, F; Garcia, J; Picus, J; et al. (AMER ASSOC CANCER RESEARCH, 2019-08-01)PURPOSE: Onalespib is a potent, fragment-derived second-generation HSP90 inhibitor with preclinical activity in castration-resistant prostate cancer (CPRC) models. This phase I/II trial evaluated onalespib in combination ... -
Plasma Metabolomic Changes following PI3K Inhibition as Pharmacodynamic Biomarkers: Preclinical Discovery to Phase I Trial Evaluation.
Ang, JE; Pandher, R; Ang, JC; Asad, YJ; Henley, AT; et al. (AMER ASSOC CANCER RESEARCH, 2016-06-01)PI3K plays a key role in cellular metabolism and cancer. Using a mass spectrometry-based metabolomics platform, we discovered that plasma concentrations of 26 metabolites, including amino acids, acylcarnitines, and ... -
RNAi screen reveals synthetic lethality between cyclin G-associated kinase and FBXW7 by inducing aberrant mitoses.
Dolly, SO; Gurden, MD; Drosopoulos, K; Clarke, P; de Bono, J; et al. (NATURE PUBLISHING GROUP, 2017-09-26)BACKGROUND: F-box and WD40 repeat domain-containing 7 (FBXW7) is an E3 ubiquitin ligase involved in the ubiquitination and degradation of multiple oncogenic substrates. The tumour suppressor function is frequently lost in ... -
Second-Generation HSP90 Inhibitor Onalespib Blocks mRNA Splicing of Androgen Receptor Variant 7 in Prostate Cancer Cells.
Ferraldeschi, R; Welti, J; Powers, MV; Yuan, W; Smyth, T; et al. (AMER ASSOC CANCER RESEARCH, 2016-05-01)Resistance to available hormone therapies in prostate cancer has been associated with alternative splicing of androgen receptor (AR) and specifically, the expression of truncated and constitutively active AR variant 7 ... -
Sequencing of prostate cancers identifies new cancer genes, routes of progression and drug targets.
Wedge, DC; Gundem, G; Mitchell, T; Woodcock, DJ; Martincorena, I; et al. (NATURE PUBLISHING GROUP, 2018-05-01)Prostate cancer represents a substantial clinical challenge because it is difficult to predict outcome and advanced disease is often fatal. We sequenced the whole genomes of 112 primary and metastatic prostate cancer ... -
The kinase polypharmacology landscape of clinical PARP inhibitors.
Antolin, AA; Ameratunga, M; Banerji, U; Clarke, PA; Workman, P; et al. (NATURE PUBLISHING GROUP, 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 ...