More than 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address this hypothesis, we established a large, publicly available repository of well-characterized leukemia and lymphoma PDXs that undergo orthotopic engraftment, called the Public Repository of Xenografts (PRoXe). PRoXe includes all de-identified information relevant to the primary specimens and the PDXs derived from them. Using this repository, we demonstrate that large studies of acute leukemia PDXs that mimic human randomized clinical trials can characterize drug efficacy and generate transcriptional, functional, and proteomic biomarkers in both treatment-naive and relapsed/refractory disease.
Copyright © 2016 Elsevier Inc. All rights reserved.

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On April 14,2016 Baxalta Incorporated (NYSE:BXLT) reported that the special meeting of stockholders to adopt the merger agreement with Shire plc (LSE:SHP, NASDAQ:SHPG) will be held on May 27, 2016, at 7:00 a.m. Central Time, for shareholders of record as of the close of business on April 11, 2016 (Press release, Baxalta, APR 14, 2016, View Source [SID:1234510829]). The special meeting will be held at Baxalta’s corporate headquarters, located at 1200 Lakeside Drive, Bannockburn, Illinois 60015.

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For more information, please refer to the merger proxy on Form S-4 that Shire has filed with the Securities and Exchange Commission (SEC).

Hepcidin, a key regulator of iron metabolism, is produced mainly by interleukin-6 (IL-6) during inflammation. A mechanism linking cancer-related anemia and IL-6 through hepcidin production is suggested. To clarify the hypothesis that overproduction of IL-6 elevates hepcidin levels and contributes to the development of cancer-related anemia, we evaluated anti-IL-6 receptor antibody treatment of cancer-related anemia in an IL-6-producing human lung cancer xenograft model.
Nude mice were subcutaneously inoculated with cells of the IL-6-producing human lung cancer cell line LC-06-JCK and assessed as a model of cancer-related anemia. Mice bearing LC-06-JCK were administered rat anti-mouse IL-6 receptor antibody MR16-1 and their serum hepcidin levels and hematological parameters were determined.
LC-06-JCK-bearing mice developed anemia according to the production of human IL-6 from xenografts, with decreased values of hemoglobin, hematocrit, and mean corpuscular volume (MCV) compared to non-tumor-bearing (NTB) mice. LC-06-JCK-bearing mice showed decreased body weight and serum albumin with increased serum amyloid A. MR16-1 treatment showed significant inhibition of decreased body weight and serum albumin levels, and suppressed serum amyloid A level. There was no difference in tumor volume between MR16-1-treated mice and immunoglobulin G (IgG)-treated control mice. Decreased hemoglobin, hematocrit, and MCV in LC-06-JCK-bearing mice was significantly relieved by MR16-1 treatment. LC-06-JCK-bearing mice showed high red blood cell counts and erythropoietin levels as compared to NTB mice, whereas MR16-1 treatment did not affect their levels. Serum hepcidin and ferritin levels were statistically elevated in mice bearing LC-06-JCK. LC-06-JCK-bearing mice showed lower values of MCV, mean corpuscular hemoglobin (MCH), and serum iron as compared to NTB mice. Administration of MR16-1 to mice bearing LC-06-JCK significantly suppressed levels of both serum hepcidin and ferritin, with increased values of MCV and MCH.
Our results suggest that overproduction of hepcidin by IL-6 signaling might be a major factor that leads to functionally iron-deficient cancer-related anemia in the LC-06-JCK model. We demonstrated that inhibition of the IL-6 signaling pathway by MR16-1 treatment resulted in significant recovery of iron-deficiency anemia and alleviation of cancer-related symptoms. These results indicate that IL-6 signaling might be one possible target pathway to treat cancer-related anemia disorders.

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The hedgehog pathway inhibitor sonidegib demonstrated meaningful tumor shrinkage in more than 90% of patients with locally advanced basal cell carcinoma (BCC) or metastatic BCC in the BCC Outcomes with LDE225 Treatment study.
This report provides long-term follow-up data collected up to 12 months after the last patient was randomized.
In this multicenter, randomized, double-blind phase II study, patients were randomized 1:2 to sonidegib 200 or 800 mg. The primary end point was objective response rate assessed by central review.
Objective response rates in the 200- and 800-mg arms were 57.6% and 43.8% in locally advanced BCC and 7.7% and 17.4% in metastatic BCC, respectively. Among the 94 patients with locally advanced BCC who responded, only 18 progressed or died and more than 50% had responses lasting longer than 6 months. In addition, 4 of 5 responders with metastatic BCC maintained an objective response. Grade 3/4 adverse events and those leading to discontinuation were less frequent with sonidegib 200 versus 800 mg (38.0% vs 59.3%; 27.8% vs 37.3%, respectively).
No placebo or comparator arms were used because sonidegib demonstrated efficacy in advanced BCC in a phase I study, and the hedgehog pathway inhibitor vismodegib was not yet approved.
With longer follow-up, sonidegib demonstrated sustained tumor responses in patients with advanced BCC.
Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

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On April 14, 2016 Cancer Research UK reported that it has shortlisted nine teams for the final stages of its £20m Grand Challenge award* – the world’s most ambitious cancer grant helping scientists attack some of the hardest unanswered questions in cancer research (Press release, Cancer Research UK, APR 14, 2016, View Source [SID:1234510830]).

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World-class multi-disciplinary researchers representing 15 countries and 50 organisations have collaborated to make the shortlist**. The shortlisted teams are led by:

Professor Roy Bicknell from the University of Birmingham, UK, with collaborators from the USA, UK, Netherlands, Sweden and Switzerland will research developing vaccines to prevent non-viral cancers.
Professor Alan Rickinson from the University of Birmingham, UK with collaborators from the USA, Netherlands, UK, Australia, Germany, Switzerland, Japan and China will research how to eradicate EBV-induced cancers from the world.
Professor Sir Mike Stratton from the Wellcome Trust Sanger Institute, UK with collaborators from France, the USA and UK will research how unusual patterns of mutation are induced by different cancer-causing events.
Dr Jelle Wesseling from the Netherlands Cancer Institute, The Netherlands with collaborators from the USA, UK and Netherlands will research how to distinguish between lethal need treating and non-lethal cancers that don’t.
Dr Surinder Sahota from the University of Southampton, UK with collaborators from the USA, UK, Spain and Germany will research how to distinguish between lethal need treating and non-lethal cancers that don’t.
Professor Freddie Hamdy from the University of Oxford, UK with collaborators from Finland, the USA and UK will research how to distinguish between lethal need treating and non-lethal cancers that don’t.
Dr Josephine Bunch from the National Physical Laboratory, UK with collaborators from the UK will find a way of mapping tumour at the molecular and cellular level.
Professor Greg Hannon from the University of Cambridge, UK with collaborators from Switzerland, Ireland, Canada, the USA and UK will find a way of mapping tumour at the molecular and cellular level.
Professor Ehud Shapiro from the Weizmann Institute, Israel with collaborators from Israel, the UK and USA will find a way of mapping tumour at the molecular and cellular level.
Sir Harpal Kumar, Cancer Research UK’s chief executive, said: "One of the driving forces behind our Grand Challenge is the ambition to unite researchers from all sciences around the world so that they can come up with game-changing ideas to solve cancer’s most challenging questions. We’re delighted that our shortlist includes so many talented, multi-disciplinary teams.

"We’ll award at least one of these teams the first ever Grand Challenge later this year and hope that this global approach will go on to help the 14.1 million people diagnosed with cancer around the world annually."

Jim Elliott, member of the Grand Challenge patient panel, said: "When reviewing the applications for the Grand Challenge initiative I was struck by scientists’ enthusiasm to work with people they hadn’t worked with before to tackle the challenges in new ways. Some of the teams were really pioneering – spanning the globe and the sciences. I’m honoured to have been part of this innovative way to research cancer and for the opportunity to make sure that the research coming out of Grand Challenge puts patients at the heart of things."