Gatehouse Park

Waltham, MA, United States

Gatehouse Park

Waltham, MA, United States
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Davies B.R.,Astrazeneca | Guan N.,Gatehouse Park | Logie A.,Astrazeneca | Crafter C.,Astrazeneca | And 12 more authors.
Molecular Cancer Therapeutics | Year: 2015

AKT1E17K mutations occur at low frequency in a variety of solid tumors, including those of the breast and urinary bladder. Although this mutation has been shown to transform rodent cells in culture, it was found to be less oncogenic than PIK3CA mutations in breast epithelial cells. Moreover, the therapeutic potential of AKT inhibitors in human tumors with an endogenous AKT1E17K mutation is not known. Expression of exogenous copies of AKT1E17K in MCF10A breast epithelial cells increased phosphorylation of AKT and its substrates, induced colony formation in soft agar, and formation of lesions in the mammary fat pad of immunodeficient mice. These effects were inhibited by the allosteric and catalytic AKT inhibitors MK-2206 and AZD5363, respectively. Both AKT inhibitors caused highly significant growth inhibition of breast cancer explant models with AKT1E17K mutation. Furthermore, in a phase I clinical study, the catalytic Akt inhibitor AZD5363 induced partial responses in patients with breast and ovarian cancer with tumors containing AKT1E17K mutations. In MGH-U3 bladder cancer xenografts, which contain both AKT1E17K and FGFR3Y373C mutations, AZD5363 monotherapy did not significantly reduce tumor growth, but tumor regression was observed in combination with the FGFR inhibitor AZD4547. The data show that tumors with AKT1E17K mutations are rational therapeutic targets for AKT inhibitors, although combinations with other targeted agents may be required where activating oncogenic mutations of other proteins are present in the same tumor. © 2015 American Association for Cancer Research.


PubMed | National Cancer Center Hospital, Gatehouse Park and Astrazeneca
Type: Clinical Trial, Phase I | Journal: Molecular cancer therapeutics | Year: 2015

AKT1(E17K) mutations occur at low frequency in a variety of solid tumors, including those of the breast and urinary bladder. Although this mutation has been shown to transform rodent cells in culture, it was found to be less oncogenic than PIK3CA mutations in breast epithelial cells. Moreover, the therapeutic potential of AKT inhibitors in human tumors with an endogenous AKT1(E17K) mutation is not known. Expression of exogenous copies of AKT1(E17K) in MCF10A breast epithelial cells increased phosphorylation of AKT and its substrates, induced colony formation in soft agar, and formation of lesions in the mammary fat pad of immunodeficient mice. These effects were inhibited by the allosteric and catalytic AKT inhibitors MK-2206 and AZD5363, respectively. Both AKT inhibitors caused highly significant growth inhibition of breast cancer explant models with AKT1(E17K) mutation. Furthermore, in a phase I clinical study, the catalytic Akt inhibitor AZD5363 induced partial responses in patients with breast and ovarian cancer with tumors containing AKT1(E17K) mutations. In MGH-U3 bladder cancer xenografts, which contain both AKT1(E17K) and FGFR3(Y373C) mutations, AZD5363 monotherapy did not significantly reduce tumor growth, but tumor regression was observed in combination with the FGFR inhibitor AZD4547. The data show that tumors with AKT1(E17K) mutations are rational therapeutic targets for AKT inhibitors, although combinations with other targeted agents may be required where activating oncogenic mutations of other proteins are present in the same tumor.


News Article | October 28, 2016
Site: www.prweb.com

Persomics USA Inc. delivers innovative biotech solutions that accelerate and increase the scale of functional genomics research. To ensure adequate capacity for production and product development, Persomics is increasing its working space threefold. The expanded lab space will support Persomics’ roll-out of the ImagineArray™ platform of miniaturized functional genomics screens produced through the company’s patented printing technology. Persomics placed its US headquarters at AstraZeneca’s Biohub in Gatehouse Park in 2014. The high quality facilities and proximity to many biotech and life science companies in the Boston area made the Waltham AZ Biohub an attractive option.    “The Gatehouse Park BioHub has been ideal for us so far, and we are pleased to be able to expand our lab footprint without moving to another location. With AstraZeneca’s support we have been able to establish a purpose-built lab of the absolute highest standards.” – Neil Emans, PhD, CEO, Persomics USA   Persomics is currently extending the ImagineArray™ platform to CRISPR/CAS9. Announcement of further products is expected 2017, pending final validation of ongoing research and development. “Persomics was one of the first companies we invited to the Biohub and it has been a pleasure to follow the progress of the company. The team contributes to our ambition of creating a more open research environment where our scientists can interact and push the boundaries of science.” – Kenneth Sutton, Director Facility Management, AstraZeneca Waltham.      About Persomics ImagineArray™ Persomics ImagineArray™ brings functional genomics screens into ordinary labs and gives every researcher the ability to conduct screens regardless of lab infrastructure. The Persomics platform allows scientists to push research further and faster, and opens up new and exciting paths to finding innovative cures. With Persomics ImagineArray™, experiments are contact-printed as spots on a glass slip. Each spot encapsulates RNA and the reagents required for gene silencing and editing. Each ImagineArray™ can hold up to 3,200 experiments on an area of just 1.3 sq. in. (8.6 cm2). The experiments are printed in parallel, by a single print head in just 2.5 seconds, using Persomics’ patented printing technology. Please see contact info for further inquiries.

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