The epidermal growth factor receptor (EGFR) abnormalities including amplification, mutation, and overexpression are frequent in non-small cell lung cancer (NSCLC). We investigated in vitro and in vivo antitumor activity of ER2, a novel human anti-EGFR monoclonal antibody, in NSCLC.
A panel of NSCLC cell lines (A549, H460, H322, H358, H1299, HCC827, PC9, H1975, and PC9-GR) was used to evaluate in vitro antitumor activity of ER2 and cetuximab. The inhibitory effects of ER2 and cetuximab on downstream signaling were assessed by western blot. Secreted VEGF was measured by Human VEGF Quantikine ELISA kit. Antitumor effects of ER2 and cetuximab as single agents and in combination with cisplatin were evaluated in H322, HCC827 and A549 xenograft models.
ER2 efficiently inhibits EGFR and its downstream signaling molecules including Akt and Erk1/2 in NSCLC cell lines with wild-type or mutant EGFR. ER2 inhibited cell viability of H322, HCC827 and A549 cells in a dose-dependent manner by inducing cell cycle arrest and apoptosis. Also, ER2 suppressed EGF-stimulated VEGF production as efficiently as cetuximab in H322, HCC827 and A549 cells. Moreover, ER2 alone and in combination with cisplatin showed a significant anti-tumor efficacy in xenograft mouse models.
Taken together, ER2 has significant anti-tumor activity in in vitro and in vivo NSCLC models, suggesting a rationale for clinical development of ER2 in NSCLC.
Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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Introduction E7820 is an orally administered sulfonamide that inhibits alfa-2-integrin mRNA expression. Pre-clinically E7820 showed tumor anti-angiogenic effects in various tumor cell lines and xenograft mouse models. Human daily dosing of 100 mg QD had previously been shown to be safe and tolerable. Methods The study consisted of two parts: Part A (food effect) and Part B (determination of maximum tolerated dose (MTD) for bi-daily (BID) dosing). E7820 dosing started at 50 mg BID with planned escalation to 60, 80 and 100 mg BID every 28 days. Results Fifteen patients were enrolled in Part A and 26 in Part B. The most frequent adverse events of all grades were constipation, diarrhea, nausea, and fatigue while anemia, neutropenia, and fatigue were most frequent grade ≥3 toxicities. At dose-level 60 mg BID, two patients experienced dose-limiting toxicities (grade 3 neutropenic sepsis and grade 4 neutropenia). Therefore the recommended dose (RD) was 50 mg BID. Food had no effect on E7820 exposure. E7820 exposure following twice daily administration was dose-proportional. Expression of platelet integrin-α2 measured as a response biomarker in Part B, generally decreased by a median 7.7 % from baseline following treatment with 50 mg BID E7820. Reduction was most pronounced within 1-week post treatment. The median duration of treatment was median 54, range 20-111 days. The best overall response in any treatment group was stable disease (SD): 23.1 % in Part A (100 mg QD); at the RD 66.7 % (12 of 18 patients) and 40 % in the 60 mg BID group in Part B.
Food had no effect on E7820 exposure. A dose of 50 mg BID was considered the MTD. Treatment with E7820 is safe and tolerable with 2/3 of patients (66.7 %) at MTD having SD as their best response.

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Many patients with acromegaly do not achieve biochemical control with first-generation somatostatin analogues. A large, multicenter, randomized, Phase III core study demonstrated that pasireotide LAR had significantly superior efficacy over octreotide LAR. This analysis explores the efficacy and safety of switching therapeutic arms in inadequately controlled patients during a 12-month crossover extension.
Patients with inadequate biochemical control (GH ≥2.5 μg/L and/or IGF-1 > ULN) at end of core study (month 12) were eligible to switch to pasireotide LAR 40 mg/28 days (n = 81) or octreotide LAR 20 mg/28 days (n = 38). One dose escalation to pasireotide LAR 60 mg/28 days or octreotide LAR 30 mg/28 days was permitted, but not mandatory, at month 17 or 20.
Twelve months after crossover, 17.3 % of pasireotide LAR and 0 % of octreotide LAR patients achieved GH <2.5 μg/L and normal IGF-1 (main outcome measure); 27.2 and 5.3 % of pasireotide LAR and octreotide LAR patients achieved normal IGF-1, respectively; 44.4 and 23.7 % of pasireotide LAR and octreotide LAR patients achieved GH <2.5 μg/L, respectively. Mean (±SD) tumor volume further decreased from the end of the core study by 25 % (±25) and 18 % (±28); 54.3 % of pasireotide LAR and 42.3 % of octreotide LAR patients achieved significant (≥20 %) tumor volume reduction during the extension. The safety profile of pasireotide LAR was similar to that of octreotide LAR, with the exception of the frequency and degree of hyperglycemia-related adverse events.
Pasireotide LAR is a promising treatment option for patients with acromegaly inadequately controlled with the first-generation somatostatin analogue octreotide LAR.
clinicaltrials.gov, NCT00600886 . Registered 14 January 2008.

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On April 4, 2016 The National Cancer Institute (NCI), part of the National Institutes of Health, reported a Blue Ribbon Panel of scientific experts, cancer leaders, and patient advocates that will inform the scientific direction and goals at NCI of Vice President Joe Biden’s National Cancer Moonshot Initiative (Press release, US NCI, APR 4, 2016, View Source [SID:1234510392]). The panel will serve as a working group of the presidentially appointed National Cancer Advisory Board (NCAB) and will provide scientific guidance from thought-leaders in the cancer community.

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"This Blue Ribbon Panel will ensure that, as NIH allocates new resources through the Moonshot, decisions will be grounded in the best science," said the Vice President. "I look forward to working with this panel and many others involved with the Moonshot to make unprecedented improvements in prevention, diagnosis, and treatment of cancer."

Over the next several months, the panel will consider how to advance the themes that have been proposed for the initiative. The themes include the development of cancer vaccines, highly sensitive approaches to early detection, advances in immunotherapy and combination therapies, single-cell genomic profiling of cancer cells and cells in the tumor microenvironment, enhanced data sharing, and new approaches to the treatment of pediatric cancers.

In addition, the cancer community, including the American public, will be provided a forum to post comments and insights to help inform the panel’s deliberations. Findings of the panel will be reported to the NCAB, which in turn will make its recommendations to NCI and contribute to the overall approach of the initiative.

"Thanks to advances in science, we are now in a historically unique position to make profound improvements in the way we treat, detect, and prevent cancer," said NIH Director Francis S. Collins, M.D., Ph.D. "The Vice President’s deep personal commitment to this noble cause will make a tremendous difference in our ability to lift the terrible burden of cancer. His call to action, including the establishment of this panel, comes at just the right time for all the right reasons."

"The Vice President’s enthusiasm about this effort is welcomed by the community of researchers, health professionals, and patients who share his passion and belief that great things are possible by accelerating cancer research with leadership and resources," said NCI Acting Director Douglas Lowy, M.D. "We are committed to breaking down silos and stimulating the groundbreaking work already underway. To be successful, we must hear a broad range of perspectives to take full advantage of the exceptional current opportunities in cancer research."

The Blue Ribbon Panel members represent a spectrum of scientific areas, including biology, immunology, genomics, diagnostics, bioinformatics, and cancer prevention and treatment. Scientific members also include investigators with expertise in clinical trials and cancer health disparities. Importantly, the members of cancer advocacy groups and pharmaceutical and biotechnology companies will be represented on the panel and its working groups.

The members of the Blue Ribbon Panel are:

Tyler Jacks, Ph.D. (Co-Chair)
Chair, National Cancer Advisory Board, and Director, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge

Elizabeth Jaffee, M.D. (Co-Chair)
Professor and Deputy Director for Translational Research, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore

Dinah Singer, Ph.D. (Co-Chair)
Acting Deputy Director and Director, Division of Cancer Biology, National Cancer Institute, Bethesda, Maryland

Peter Adamson, M.D.
Professor and Director, Experimental Therapeutics in Oncology, The Children’s Hospital of Philadelphia

James Allison, Ph.D.
Professor and Chair of Immunology, University of Texas MD Anderson Cancer Center, Houston

David Arons, J.D.
Chief Executive Officer, National Brain Tumor Society, Newton, Massachusetts

Mary Beckerle, Ph.D.
CEO and Director, Huntsman Cancer Institute, Salt Lake City

Mitch Berger, M.D.
Professor and Chair, Department of Neurological Surgery, University of California, San Francisco

Jeff Bluestone, Ph.D.
Executive Vice Chancellor and Provost, University of California, San Francisco

Mikael Dolsten, M.D., Ph.D.
President, Pfizer Worldwide Research and Development, and Executive Vice President, Pfizer, Inc., New York

James Downing, M.D.
President and CEO, St. Jude Children’s Research Hospital, Memphis, Tennessee

Levi Garraway, M.D., Ph.D.
Associate Professor of Medicine, Harvard Medical School, and Assistant Professor of Medicine, Dana-Farber Cancer Institute, Boston

Gad Getz, Ph.D.
Director, Cancer Genome Computational Analysis Group, Broad Institute of MIT and Harvard, Cambridge, Massachusetts

Laurie Glimcher, M.D.
Professor of Medicine and Dean, Weill Cornell Medical College, and Incoming President and CEO, Dana-Farber Cancer Institute, Boston

Lifang Hou, M.D., Ph.D.
Associate Professor of Preventive Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago

Neal Kassell, M.D.
Professor of Neurosurgery, University of Virginia, Charlottesville

Maria Elena Martinez, Ph.D.
Professor of Family Medicine and Public Health, Reducing Cancer Disparities Program, UC San Diego Moores Cancer Center

Deborah Mayer, Ph.D., R.N.
Professor of Adult and Geriatric Health, University of North Carolina School of Nursing, and Director of Cancer Survivorship, UNC Lineberger Comprehensive Cancer Center, Chapel Hill

Edith Mitchell, M.D., F.A.C.P
Professor of Medical Oncology and Associate Director for Diversity Services, Sidney Kimmel Cancer Center at Thomas Jefferson University, Philadelphia

Augusto Ochoa, M.D.
Professor of Pediatrics and Director, Stanley S. Scott Cancer Center, Louisiana State University, New Orleans

Jennifer Pietenpol, Ph.D.
Professor of Biochemistry and Director, Vanderbilt-Ingram Cancer Center, Nashville

Angel Pizarro, M.S.E.
Technical Business Development Manager, Amazon Web Services Scientific Computing and Research Computing, Philadelphia

Barbara Rimer, Dr.P.H.
Alumni Distinguished Professor and Dean, University of North Carolina Gillings School of Global Public Health, Chapel Hill

Charles Sawyers, M.D.
Chair, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, and Investigator, Howard Hughes Medical Institute, New York

Ellen Sigal, Ph.D.
Founder and Chair, Friends of Cancer Research, Washington, DC

Patrick Soon-Shiong, M.B.B.Ch.
Founder, Chair, and CEO, NantWorks LLC, Los Angeles

Chi Van Dang, M.D., Ph.D.
Professor of Medicine and Director, Abramson Cancer Center, University of Pennsylvania, Philadelphia

Wai-Kwan Alfred Yung, M.D.
Professor of Neuro-Oncology and Chair of Clinical Cancer Care, University of Texas MD Anderson Cancer Center, Houston

The NCAB will advise the NCI director based on its consideration of the Blue Ribbon Panel’s recommendations, expected to be delivered later this summer. A final report by the White House Cancer Moonshot Task Force, chaired by Vice President Biden, will be produced and delivered to President Barack Obama by Dec. 31, 2016.

To meet its milestones, the panel will begin its work immediately, convening its first meeting in the coming weeks. The panel will also consider public comments over the next several months prior to making its recommendations.

Members of the research community and the public can engage in the initiative initially by subscribing to updates on the initiative’s main website (www.cancer.gov/moonshot-cancer-initiative) or by emailing the panel at [email protected]. In addition, an online forum for submitting scientific ideas and comments to the panel will be available on the site in the coming weeks.