Glioblastomas always recur despite surgery, radiotherapy and chemotherapy. A key player in the therapeutic resistance may be immature tumor cells with stem-like properties (TSCs) escaping conventional treatment. A group of promising molecular targets are microRNAs (miRs). miRs are small non-coding RNAs exerting post-transcriptional regulation of gene expression. In this study we aimed to identify over-expressed TSC-related miRs potentially amenable for therapeutic targeting. We used non-differentiated glioblastoma spheroid cultures (GSCs) containing TSCs and compared these to xenografts using a NanoString nCounter platform. This revealed 19 over-expressed miRs in the non-differentiated GSCs. Additionally, non-differentiated GSCs were compared to neural stem cells (NSCs) using a microarray platform. This revealed four significantly over-expressed miRs in the non-differentiated GSCs in comparison to the NSCs. The three most over-expressed miRs in the non-differentiated GSCs compared to xenografts were miR-126, -137 and -128. KEGG pathway analysis suggested the main biological function of these over-expressed miRs to be cell-cycle arrest and diminished proliferation. To functionally validate the profiling results suggesting association of these miRs with stem-like properties, experimental over-expression of miR-128 was performed. A consecutive limiting dilution assay confirmed a significantly elevated spheroid formation in the miR-128 over-expressing cells. This may provide potential therapeutic targets for anti-miRs to identify novel treatment options for GBM patients.

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On April 12, 2016 Rigel Pharmaceuticals, Inc. (Nasdaq:RIGL) reported that it will present three scientific posters at the American Association of Cancer Research meeting in New Orleans, Louisiana from April 16 – 20, 2016 (Press release, Rigel, APR 12, 2016, View Source;p=RssLanding&cat=news&id=2156237 [SID:1234510707]). The posters will provide data from the company’s preclinical research projects focused on the important oncology and immuno-oncology targets, IRAK, AMPK and MerTK. Rigel plans to partner select preclinical research programs in the future.

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An overview of each project and the corresponding AACR (Free AACR Whitepaper) presentation information follows:

IRAK
Rigel has an active IRAK preclinical research program aimed at understanding the role that certain inflammatory signals play in creating malignant changes in cells. IRAKs are key components in the signal transduction pathways associated with inflammation in humans. The company’s researchers have identified a family of IRAK4 inhibitors that are potent regulators of the inflammatory signal and are being evaluated for their potential utility in treating hematological cancers.

Abstract #: 346
Presentation Title: Potential role for R191, potent and selective IRAK4 kinase inhibitor, in treatment of hematological malignancies
Presentation Date: Sunday, April 17, 1:00pm – 5:00pm
Location: Section 17
Poster Board #: 2

AMPK
AMPK is a master regulator of cellular energy homeostasis and is an attractive research subject for its role in the metabolism of certain cancers, and other human diseases. Rigel has identified several potent direct AMPK activators, and is evaluating their potential to selectively activate AMPK within certain cancer cells to make them susceptible to the destructive properties of chemotherapeutic agents.

Abstract #: 3021
Presentation Title: Development of small molecule direct AMPK activators for the treatment of cancer
Presentation Time: Tuesday, April 19, 8:00am – 12:00pm
Location: Section 17
Poster Board #: 11

MerTK
Mer is a member of the TAM kinase family (Tyro3, AXL, Mer) known to provide tumor survival signals and support immunosuppressive tumor microenvironments. Rigel’s research on this family of receptor tyrosine kinases, also produced the AXL kinase inhibitor (R428/BGB324) currently in Phase 1 oncology studies with partner BerGenBio. The subject of the AACR (Free AACR Whitepaper) presentation is the company’s work with proprietary, orally delivered small molecules that block MerTK activity in vivo.

Abstract #: 4869
Presentation Title: Small molecule inhibitors of the anti-inflammatory TAM receptor MerTK
Presentation Time: Wednesday, April 20, 8:00am – 12:00pm
Location: Section 22
Poster Board #: 10

On April 12, 2016 OncoSec Medical Incorporated ("OncoSec") (NASDAQ: ONCS), a company developing DNA-based intratumoral cancer immunotherapies, reported that preclinical results from OncoSec’s collaboration with Heat Biologics, Inc. will be featured as a poster presentation at the upcoming American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting to be held on April 16-20, 2016 in New Orleans, LA (Press release, OncoSec Medical, APR 12, 2016, View Source [SID:1234510706]).

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Details of the poster presentation are as follows:

Abstract Title: In vivo intra-tumoral electroporation of Gp96-Ig/Fc-OX40L stimulates CD8+ T cell cross-priming to tumor specific neoantigens (Abstract ID #567)
Session Title: Immune Modulating Agents 1
Date and Time: April 17, 2016 at 1:00 p.m. – 5:00 p.m. CT
Location: Section 26

On April 12, 2016 Biota Pharmaceuticals, Inc. (NASDAQ:BOTA) reported that the Company has changed its name to Aviragen Therapeutics, Inc., ("Aviragen Therapeutics"), a pharmaceutical company focused on the development of the next generation of direct-acting antivirals that address infections that have limited therapeutic options (Press release, Aviragen Therapeutics, APR 12, 2016, View Source [SID1234510705]).

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"A meaningful transformation has taken place over the last two years as we transitioned from a drug discovery and early-stage licensing organization to one focused on drug development and progressing key late-stage product candidates in important viral diseases. Our name change reflects this transition and better defines our strategic initiatives moving forward," said Joseph Patti, PhD, President and Chief Executive Officer of Aviragen Therapeutics. "Specifically, our recent initiation of a Phase 2a efficacy study of BTA585 for the treatment of RSV infections highlights our focus on bringing new medicines to treat and prevent viral infections with limited therapeutics options. As Aviragen Therapeutics, we will continue to advance and expand our promising pipeline of anti-viral drugs."

The name change become effective on April 11, 2016 and the Company’s common stock will begin trading on the NASDAQ Stock Exchange under the new ticker symbol "AVIR" on April 13, 2016. The Company will have a new website address: www.aviragentherapeutics.com.

On April 12, 2016 Clovis Oncology, Inc. (NASDAQ: CLVS) reported that NASDAQ has halted trading of the Company’s common stock (Press release, Clovis Oncology, APR 12, 2016, View Source;p=RssLanding&cat=news&id=2156231 [SID:1234510704]). The U.S. Food and Drug Administration’s (FDA) Oncologic Drugs Advisory Committee (ODAC) is meeting this morning to discuss the company’s New Drug Application (NDA) for rociletinib for the treatment of patients with mutant epidermal growth factor receptor (EGFR) non-small cell lung cancer (NSCLC) who have been previously treated with an EGFR-targeted therapy and have the EGFR T790M mutation.

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About Rociletinib
Rociletinib is the company’s novel, oral, targeted covalent (irreversible) mutant-selective inhibitor of EGFR in development for the treatment of NSCLC in patients with initial activating EGFR mutations, as well as the dominant resistance mutation T790M. Data from both the pivotal, single-arm TIGER-X and TIGER-2 clinical trials served as the basis for the U.S. and EU regulatory submissions for the treatment of advanced mutant EGFR T790M-positive lung cancer. Rociletinib was granted Breakthrough Therapy designation by the FDA in May 2014.