Category Archives: Pharmacogenomics

MORRISVILLE, N.C., July 12, 2012 /PRNewswire/ -- Gentris Corporation (www.gentris.com), a global leader in pharmacogenomics and biorepository services, announced today that it has expanded its genomic biomarker services by incorporating multiple technology platforms into its 24,000 sq. ft., CLIA-certified, GLP-compliant laboratory. Gentris has integrated the Affymetrix GCS3000, Sequenom MassArray, and LifeTech Ion Torrent technologies in a continued effort to identify polymorphisms involved in drug response and adverse drug events as well as in determining somatic mutations in cancer.

Gentris has utilized Affymetrix DMET Plus analysis in a number of clinical studies, including oncology clinical trials. DMET Plus analysis allows drug developers to understand how variations in drug metabolism enzymes and drug transporters between patients affects adverse drug responses and treatment efficacy. This type of analysis has been implemented by major pharmaceutical companies in Phase I through Phase III clinical trials focused on numerous therapeutic areas. Most recently, Gentris collaborated with Dr. Howard McLeod of UNC-Chapel Hill to assess the risk of sensory neuropathy in breast cancer patients with genetic variations in drug metabolizing enzymes.

With the integration of Sequenom's MassArray, Gentris is able to design customizable, multiplex panels of genes for use in clinical trials. The Company has already designed a custom panel for a top ten pharmaceutical company. In addition, Gentris offers the iPLEX ADME PGx panel, which examines 192 of the most common variants in 36 ADME genes; the OncoCarta Panel v1.0, which is a comprehensive screen of 19 oncogenes and 238 mutations; and the Sequenom Sample ID Plus panel, which ensures that chain of custody is maintained and that there is amplifiable DNA in the sample.

The latest platform to be brought online is LifeTech's Ion Torrent Personal Genome Machine (PGM) for next generation sequencing. The Ion Torrent PGM allows for rapid, deep sequencing of large areas of the genome, which can efficiently identify both common and rare variations that may better predict the safety and efficacy of new drugs in development. Currently, Gentris is using the Ion Torrent PGM for discovery initiatives with its pharmaceutical partners as well as part of a collaboration with UNC-Chapel Hill.

Related Links: http://www.gentris.com

Quotes:

"The expansion of our services by using these platform technologies allows us to provide our clients quality and regulated services in all phases of the clinical development pipeline," said Dr. L.Scott Clark, Gentris Chief Scientific Officer. "It's very exciting to use the Ion Torrent for discovery initiatives, because the depth of coverage and resolution can reveal new SNPs and variations that may be clinically relevant. However, these results need to be verified on a second platform which Gentris can perform because of its extensive experience with real-time PCR, Sanger sequencing, and Sequenom platforms."

"The key to successfully implementing pharmacogenomics is to use the right platform to answer your specific question," said Dr. Howard McLeod, Director of the UNC Institute for Pharmacogenomics and Individualized Therapy and Gentris Chief Scientific Advisor. "By integrating multiple platforms, Gentris has the ability to address the needs of pharmaceutical clients during any stage in the clinical development of a drug. I'm excited to be working with them to discover, translate, and validate new biomarkers that will have an impact on patient care."

About Gentris Corporation:

Founded in 2001, Gentris is located in Research Triangle Park, NC, where it provides pharmacogenomics and biorepository support for all phases of clinical studies and genomic biomarker programs. The Company works with academic and industry leaders to translate innovations in pharmacogenomics into safer, more effective medicines, which can lead to accelerated drug development and improvement in patient care globally.

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Gentris Corporation Launches New Pharmacogenomics Services

Home national Life-sciences team forms new partnerships at US event

The Nation July 3, 2012 1:00 am

The collaborative project with the US is aimed at developing "probe capture assay" applications on next-generation DNA-sequencing technologies for HIV-1 pharmacogenomics, the most advanced of its kind in the world. It will put new tools for diagnosing both human and virus genomes in the hands of front-line physicians, and bring clear benefits to patients.

The 2012 BIO International Convention held last week in Boston, Massachusetts drew 20,000 participants including researchers, scientists, investors and businessmen from both the public and private sectors. TCELS led a team of Thai delegates from allied agencies including the Board of Investment (BoI), National Nanotechnology Centre (Nanotec) and Naresuan University. Works by Thai researchers were presented at the Thai Pavilion.

TCELS presented projects under its support including a whitening product made from natural latex extracted by Prince of Songkla University; the discovery of genes allergic to the anti-retroviral drugs Nevirapine and d4T (a world first discovery by the Pharmaco-genomics Project at Ramathibodi Hospital with Mahidol University); and other pre-clinical and clinical research developments that meet international standards. This is to prove the country's potential in research collaboration and services.

TCELS acting head Kamchorn Balangura said that over the four-day event, more than 700 visitors showed their interest and sought details about Bio-Nanotechnology investment, standard clinical research and development, as well as Thai life-science products.

Kamchorn said the event was a great success for Thailand, as the team was able to establish tie-ups with counterparts from major countries in the field like South Korea and the US. The Chuncheon Bioindustry Foundation (CBF), a South Korean regional industrial estate, is interested in integrating research in the industry, and has already signed an MoU with Thailand.

US biotechnological firm Pathogenica, which works on advanced DNA-sequencing technologies, also agreed to sign an MOU to collaborate with the TCELS-supported Pharmaco-genomics Project.

Prof Wasun Chantratita, head of the Pharmacogenomics Project, said Dr Yemi Adesokan, the chief of Pathogenica, had followed Thai research on pharmacogenomics for a while and expressed an interest in establishing a collaboration. After learning that the Pharmaco-genomics team was at the convention, talks were held and the groups agreed to work together.

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Life-sciences team forms new partnerships at US event

LEXINGTON, Mass.--(BUSINESS WIRE)--

Synta Pharmaceuticals Corp. (SNTA) today announced encouraging results from a planned interim analysis of the GALAXY trial, a randomized Phase 2b/3 study designed to evaluate the efficacy and safety of the Companys lead Hsp90 inhibitor, ganetespib, in combination with standard-of-care docetaxel vs. docetaxel alone as second-line treatment for advanced non-small cell lung cancer (NSCLC).

The GALAXY trial is based on a two-stage, operationally adaptive design. The first-stage, randomized, open-label, 240-patient Phase 2b portion of the trial is designed to enroll Stage IIIB/IV NSCLC patients who have progressed following one prior line of therapy, with the goal of determining biomarkers predictive of ganetespib activity. Results will be used to guide choice of patient population for the Phase 3 stage of the trial.

Patients in the GALAXY trial are randomized 1:1 to receive ganetespib plus docetaxel or docetaxel alone. Patients in both arms receive a standard regimen of docetaxel 75 mg/m2 on day 1 of a 21-day cycle; patients in the combination arm receive in addition ganetespib 150 mg/m2 on days 1 and 15. Treatment continues until disease progression per RECIST 1.1 criteria.

The co-primary endpoints of GALAXY are PFS (progression-free survival) in patients with elevated baseline level of serum LDH (lactate dehydrogenase), and PFS in the mutant KRAS population. PFS and OS (overall survival) in all adenocarcinoma patients are key secondary endpoints. Serum LDH levels and tumor KRAS mutation status are assessed by independent central laboratories.

Elevated LDH: Elevated baseline LDH occurs in approximately one quarter to one third of advanced cancer patients in clinical trials and is prognostic of poor clinical outcomes in many cancer types, including lung cancer.[1-3] While elevated LDH can result from several conditions, in cancer patients elevated levels of LDH and its isoforms have been associated with tumor hypoxia (lack of oxygen).[4,5] Inhibition of hypoxia pathways has been shown to enhance anti-cancer activity of taxanes and other chemotherapies.[6] Recent results from trials evaluating agents that target hypoxia-related pathways, including VEGF and mTOR inhibitors, have shown correlation between elevated LDH and improved clinical activity.[7-10] In laboratory experiments, treatment with ganetespib potently suppresses HIF-1alpha, a critical regulator of hypoxic pathways[11] supporting potential application for ganetespib in combination with taxanes in this patient population.

KRAS mutation: Activating KRAS mutations, estimated to occur in 15-30% of NSCLC patients, are also associated with poor clinical outcomes and limited therapeutic options.[12,13] Hsp90 is required for the proper function of a number of key signaling proteins in the KRAS pathway, while inhibition of Hsp90 by ganetespib has shown promising activity in laboratory models of this disease.[14] Recent results from trials evaluating ganetespib monotherapy in lung, colon, and gastric cancers have further suggested promising potential in patients with KRAS mutations.

Based on a target enrollment of 240 adenocarcinoma patients, GALAXY is 90% powered to detect a PFS improvement from 6 to 12 weeks in elevated LDH patients and from 5 weeks to 10 weeks in the mutant KRAS patients. For the key secondary endpoints: in all adenocarcinoma patients, GALAXY is 88% powered to detect an improvement in PFS from 3 to 4.5 months, and 73% powered to detect an improvement in OS from 6 to 8.5 months. All powering assumptions are based on a 1-sided alpha of 0.05. An interim analysis was planned when approximately 50% of patients had been enrolled and had sufficient follow up, defined as one post-baseline scan.

GALAXY Interim Results

At the time of this interim analysis, a total of 114 adenocarcinoma and 69 non-adenocarcinoma patients had been enrolled. Following a review earlier this year that determined low likelihood of benefit in the non-adenocarcinoma population, the trial was modified to enroll only adenocarcinoma patients. Results reported below are for adenocarcinoma patients only.

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Synta Announces Results from Interim Analysis of the Randomized Phase 2b/3 GALAXY Trial Evaluating Ganetespib plus ...

DUBLIN--(BUSINESS WIRE)--

Research and Markets (http://www.researchandmarkets.com/research/h3n97n/companion_diagnost) has announced the addition of the "Companion Diagnostics in Personalized Medicine and Cancer Therapy" report to their offering.

Companion diagnostics (CDx) refers to a particular clinical diagnostic test that is under evaluation and is specifically linked to a known drug therapy. This linkage could be important in the therapeutic application and clinical outcome of a drug, such as with personalized medicine for oncology patients. The molecular diagnostics field plays a vital part in personalized medicine and has greatly expanded over the past twenty years, expanding by more than 20% annually compared to most other laboratory procedures. Research will continue to produce an increased understanding of disease processes, and diagnostics manufacturers will continue to expand and refine the technology and automation needed for clinical testing. Companion diagnostics, although smaller at present, is one of the fastest growing segments in the in vitro diagnostic (IVD) market. And while the concept of a drug-diagnostic combination is not new, it has only recently started to generate interest with the move of healthcare towards pharmacogenomics.

This TriMark Publications report examines the use of companion diagnostics in personalized medicine and cancer therapy. The study provides a qualitative and quantitative review of the industry, including cancer biomarker tests, pharmacogenomics tests, recurrence prediction tests, blood-based technologies, proteomics and regulatory trends. Moreover, this analysis profiles the leading companies that are developing and manufacturing companion diagnostics solutions. Each company is discussed in extensive depth with a section on its history, product line, business and marketing analysis, and a subjective commentary of the company's market position. Detailed tables and charts with sales forecasts and market share data are also included.

Key Topics Covered:

1. Overview

2. Companion Diagnostics and Personalized Medicine

3. Companion Diagnostics: Qualitative and Quantitative Market Analysis

4. Trends and Overview

5. Biomarker Tests Co-developed with Cancer Therapeutics as Companion Diagnostics

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Research and Markets: Companion Diagnostics in Personalized Medicine and Cancer Therapy

MELBOURNE, Australia, June 26, 2012 /PRNewswire/ --Circadian Technologies Limited (ASX: CIR, OTCQX: CKDXY) announces that it has been advised by its development partner, Healthscope Advanced Pathology, that it will commercially launch Circadian's novel technology for aid in the diagnosis of "Cancers of Unknown Primary" (CUP), on Monday July 16 2012 in Australia, New Zealand, Singapore and Malaysia under the brand CUPGUIDE.

The diagnostic test method has been developed in collaboration between Circadian, Healthscope, the Peter MacCallum Cancer Centre, a leading specialty cancer centre, and scientists at NICTA, Australia's Information and Communications Technology (ICT) Research Centre of Excellence.

A publication in March 2012 from Healthscope reported that the CUP test was able to detect actual primary source of tumour type with 93% accuracy within the first three predictions and had 98.5% specificity across 15 different tumour types.

Healthscope, through its subsidiary Clinical Laboratories Pty Ltd, has rights to develop, clinically validate and market the test throughout Australia, New Zealand, Malaysia and Singapore. Circadian retains rights to market the test in the remainder of the world. Healthscope has paid Circadian an upfront fee, and will pay a royalty on sales of the test. Circadian, through its wholly owned subsidiary Cancer Therapeutics Limited, owns exclusive worldwide rights to the test through a licensing arrangement with the Peter MacCallum Cancer Centre and NICTA.

The CUP diagnostic methodology identifies a patient's tumour type by comparing its pattern of gene expression to a database of known tumours. It is hoped that by correctly identifying a patient's tumour type, clinicians can choose the most effective treatment strategy for the cancer. CUP is generally less well known and publicised than other cancer types. However, it is actually more common than leukaemia and is the fifth most common cause of death due to cancer in Australia. In 2007, Cancer Council Australia estimated the incidence of CUP to be around 2900 case per annum; American Cancer Society estimated USA incidence at around 32,000 per annum and Cancer Research UK estimated UK incidence at 14,000 per annum.

Robert Klupacs, Circadian Managing Director and CEO stated, "We are absolutely delighted that after all of the efforts of the collaborative partners that CUPGUIDE will now be available to oncologists and pathologists. We are extremely hopeful that CUPGUIDE will have a major impact in significantly improving the clinical diagnosis of CUP."

Dr Keith Byron, Scientific Director of Healthscope's Advanced Pathology Division said, "Healthscope is proud and excited that after the extensive development program we have undertaken with our partners that we will now be able to provide this ground breaking diagnostic technology on a commercial basis. The test is an important addition to our existing business of providing diagnostic tools for doctors throughout our 43 hospitals and the health care industry in general."

Prof David Bowtell, Head of the Cancer Genomics Program at the Peter MacCallum Cancer Centre and a co-inventor of the diagnostic methodology added, "The approach was initially developed in our lab several years ago but the assay needed to be made more generally available. Circadian and Healthscope have been critical to taking the work forward and it is very gratifying that this product of our translational research efforts will be made available to clinicians throughout the region. The concept of personalising treatments for patients based on highly specialised diagnostics is now very well accepted in oncology and has been shown to have significant patient benefit. We believe that the assay will lead to earlier diagnosis, improved treatment outcomes and enhanced quality of life for patients."

Dr Adam Kowalczyk, Leader of Diagnostic Genomics Team in NICTA's Victorian Research Laboratory, and a co-inventor of the diagnostic methodology added, "It is very satisfying that formal techniques for signal detection and pattern recognition can be utilised in practical medical applications. This diagnostic test heralds imminent arrival of many new developments bringing promises of personalised medicine and genomics, in particular, to everyday usage that benefits patients."

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Healthscope to commercially launch Circadian's Cancers of Unknown Primary Diagnostic Test

Public release date: 25-Jun-2012 [ | E-mail | Share ]

Contact: Sarah Jackson press_releases@the-jci.org Journal of Clinical Investigation

METABOLISM The skinny on what makes us fat

Obesity is a disorder in which fat cells grow larger and accumulate. Certain proteins, called WNT family proteins, function to prevent fat cell formation. However, the activity of WNT proteins can be inhibited by secreted frizzled-related proteins (SFRPs), thus leading to fat cell generation. One of these SFRPs, SFRP5, is highly expressed during fat cell generation and increases during obesity. Dr. Ormond MacDougald and colleagues at the University of Michigan sought to determine the mechanism of SFRP5-mediated obesity and found that mice lacking SFRP5 were resistant to diet-induced obesity, despite having similar numbers of fat cells as control mice. The results from a transplantation experiment wherein fat tissue was transferred from SFRP5-deficient mice into obesity-prone mice demonstrated that the mechanism of SFRP5-mediated inhibition of fat cell generation is specific to the tissue itself and not dependent on the surrounding environment. The team also found that SFRP5-deficient mice showed increased metabolic activity compared to control mice. These findings, which were discussed in a commentary by Alexander Rauch and Susanne Mandrup at the University of Southern Denmark, shed light on the mechanism of SFRP5-mediated obesity and identify the WNT signaling pathway as a potential therapeutic target to counteract obesity.

TITLE:

Regulation of adipocyte mitochondrial biogenesis and metabolism by secreted frizzled-related protein 5 and WNT signaling

AUTHOR CONTACT:

Ormond MacDougald University of Michigan, Ann Arbor, MI, USA Phone: (734) 647-7721; Fax: 734 232-8175; E-mail: macdouga@umich.edu

ACCOMPANYING COMMENTARY

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JCI early table of contents for June 25, 2012