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News Article | May 23, 2017
Site: www.eurekalert.org

DALLAS - May 23, 2017 - Patients with non-small cell lung cancer (NSCLC) often respond to standard chemotherapy, only to develop drug resistance later, and with fatal consequences. But what if doctors could identify those at greatest risk of relapse and provide a therapy to overcome or avoid it? Researchers at UT Southwestern Medical Center believe they have an answer: a 35-gene signature that identifies tumor cells most likely to develop resistance to treatment. The study, published today in Cell Reports, points to a new pharmacologic approach to target chemo-resistant lung cancer and even prevent development of such resistance in the first place. "Cancer relapse after chemotherapy poses a major obstacle to treating lung cancer, and resistance to chemotherapy is a big cause of that treatment failure," said study co-author Dr. John Minna, a Professor and Director of in the Hamon Center for Therapeutic Oncology Research at UT Southwestern. "These findings provide new insights into why resistance develops and how to overcome it." Dr. Minna, with additional appointments in Pharmacology and Internal Medicine, also holds the Sarah M. and Charles E. Seay Distinguished Chair in Cancer Research and the Max L. Thomas Distinguished Chair in Molecular Pulmonary Oncology. Investigators studied mouse and cellular models of NSCLC, a type of lung cancer that the American Cancer Society estimates accounts for 85 percent of all lung cancer cases in the United States. "Previous studies have shown that up to 70 percent of those cancers develop resistance to standard therapy, such as the platinum-taxane two-drug combo that is often given," said study senior author Dr. Elisabeth D. Martinez, Assistant Professor of Pharmacology and in the Hamon Center. Both she and Dr. Minna are also members of UTSW's Harold C. Simmons Comprehensive Cancer Center. Using long-term on/off drug cycles, lead author and former postdoctoral researcher Dr. Maithili Dalvi developed a series of cellular models of progressive tumor resistance to standard chemotherapy that ranged from very sensitive to highly insensitive. Next, the researchers identified genes commonly altered during the development of resistance across multiple cell line and mouse models and identified a 35-gene signature that indicated a higher genetic likelihood of chemotherapy resistance. "It's like a fingerprint for resistance," Dr. Martinez said, adding that it was predictive in both cells and mouse models. Next they compared this resistance biomarker using genetic profiles from human tumors in their National Cancer Institute (NCI) lung cancer Specialized Programs of Research Excellence (SPORE) database at UT MD Anderson Cancer Center in Houston. The database contained information on patient outcomes and those who had been treated with the two-drug chemotherapy. The genetic fingerprint for resistance correlated with cancer relapse in NSCLC patients in the database, she said. Researchers discovered that as cancer cells developed greater resistance to chemotherapy, they progressively made higher amounts of enzymes called JumonjiC lysine demethylases. Dr. Martinez said these enzymes facilitate resistance by changing the expression of - or turning on and off - genes. "Cancer cells use these enzymes to change, or reprogram, gene expression in order to survive the toxic stress of the chemotherapy. By changing the expression of genes, the tumor cells can adapt and survive the toxins," she said. Investigators then tested two potential drugs, both JumonjiC inhibitors. One of them, JIB-04, was found by UT Southwestern researchers in the Martinez lab during a small-molecule screen conducted at the National Center for Advancing Translational Sciences' Chemical Genomics Center in Bethesda, Maryland. "I believe this is the first report of NSCLC tumors taking advantage of multiple JumonjiC enzymes to reprogram gene expression in order to survive chemotoxic stress. In addition, and this is the most fascinating part: Dr. Dalvi found that greater chemotherapy resistance defines a new susceptibility to the JumonjiC inhibitors," she said. "The cancer cells develop a new Achilles' heel that we can hit." Because the chemo-resistant cancer cells are dependent on JumonjiC enzymes for survival, inhibiting those enzymes returns cancer cells to mortality and vulnerability to cell death, she explained. "We think these JumonjiC inhibitors have the potential to be used either to treat tumors once they become resistant to standard therapies, or to prevent resistance altogether," she said. "In our experiments these inhibitors appear to be much more potent in killing cancer cells than normal cells." Later, researchers tested whether the Jumonji inhibitors JIB-04 or GSK-J4 prevented chemotherapy resistance. This strategy succeeded in cell cultures and partially prevented resistance in animal models, Dr. Martinez said. Other UT Southwestern researchers involved in this work were Dr. Luc Girard, Assistant Professor, Dr. Lei Wang, senior research associate, and Dr. Juan Bayo, postdoctoral researcher, all with the Hamon Center and of Pharmacology; Dr. Rahul Kollipara, a computational biologist in the Eugene McDermott Center for Human Growth and Development; Hyunsil Park, a research associate, and Dr. Brenda Timmons, a research scientist, both of the Hamon Center; Paul Yenerall, graduate student; Dr. Yang Xie, Associate Professor of Clinical Sciences and of Bioinformatics; Dr. Adi F. Gazdar, Professor in the Hamon Center, the Simmons Comprehensive Cancer Center, and Pathology and holder of the W. Ray Wallace Distinguished Chair in Molecular Oncology Research; and Dr. Ralf Kittler, Assistant Professor in the McDermott Center, Pharmacology, and the Simmons Comprehensive Cancer Center as well as a CPRIT Scholar and a John L. Roach Scholar in Biomedical Research. Researchers at MD Anderson Cancer Center, the Perelman School of Medicine at the University of Pennsylvania, and The Ohio State University College of Medicine also contributed. The study received support from the NCI, the Department of Defense, the Cancer Prevention and Research Institute of Texas (CPRIT), the Friends of the Cancer Center, The Welch Foundation, and an LLS Robert Arceci Scholar Award. UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution's faculty has received six Nobel Prizes, and includes 22 members of the National Academy of Sciences, 18 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The faculty of more than 2,700 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 100,000 hospitalized patients, 600,000 emergency room cases, and oversee approximately 2.2 million outpatient visits a year. This news release is available on our website at http://www. . To automatically receive news releases from UT Southwestern via email, subscribe at http://www.


RosettaGX Reveal™ Available in all 50 States PHILADELPHIA, PA and REHOVOT, ISRAEL / ACCESSWIRE / May 4, 2017 / Rosetta Genomics Ltd. (NASDAQ: ROSG), a genomic diagnostics company that improves treatment decisions by providing timely and accurate diagnostic information to physicians, announces it has received final approval for RosettaGX Reveal™ (Reveal), its novel microRNA classifier for the diagnosis of indeterminate thyroid cases from the New York State Department of Health (NYSDOH) under the Company's Molecular Oncology permit. RosettaGX Reveal is the only molecular test in the thyroid market that has been validated in a multicenter, international, blinded study using convenient, routinely prepared cytology slides. The Rosetta Laboratory is CLIA-certified, but New York State requires an additional license from the NYSDOH for Lab Developed Tests to be offered to patients in the state. The assay had previously received conditional approval and now that approval has become final. "We are very pleased to have final approval for this important cancer diagnostic for the benefit of physicians and patients in New York State. The NYSDOH has a very rigorous approval process and this final approval further confirms the overall robust performance of our Reveal assay," stated Kenneth A. Berlin, President and Chief Executive Officer of Rosetta Genomics. "Reveal is a truly differentiated assay being promoted in an established market that has substantial room for further penetration. Reveal's convenience and performance advantages are strongly resonating with clinicians, allowing us to continue to win business from the competition and to expand Reveal sales into untapped parts of the market. Continuing to have access for Reveal to the vast New York market will significantly enhance these efforts." "It is estimated that nearly 550,000 FNAs are performed on thyroid nodules each year in the U.S. and that approximately 740,000 are performed annually in Europe. Interpretation of FNA samples is not always straightforward, leading to an indeterminate result in up to 30% of the samples. Many patients with indeterminate results undergo surgery as a precaution despite the fact that up to 80% of these cases are benign. This exposes patients to unnecessary surgical risk and costs the healthcare system hundreds of millions of dollars. Through an analysis of our validation study data, we believe we can help prevent up to 75% of unnecessary thyroid surgeries," added Mr. Berlin. Rosetta is pioneering the field of molecular diagnostics by offering rapid and accurate diagnostic information that enables physicians to make more timely and informed treatment decisions to improve patient care. Rosetta has developed a portfolio of unique diagnostic solutions for oncologists, urologists, endocrinologists, cytopathologists and other specialists to help them deliver better care to their patients. RosettaGX Reveal™, a Thyroid microRNA Classifier for the diagnosis of cancer in thyroid nodules, as well as the full RosettaGX™ portfolio of cancer testing services are commercially available through the Company's Philadelphia, PA- and Lake Forest, CA-based CAP-accredited, CLIA-certified labs. Various statements in this release concerning Rosetta's future expectations, plans and prospects including, but not limited to statements relating to creating long term revenue opportunities via Reveal, achieving further market penetration and market acceptance from clinicians, expanding Reveal sales into untapped parts of the market, and growing global interest in this assay and statements containing the words "expect," "believe," "will," "may," "should," "project," "estimate," "anticipated," "scheduled," and like expressions, and the negative thereof, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various risks and uncertainties, including, but are not limited to the following: we will require substantial additional funds to continue our operations and, if additional funds are not available, we may need to significantly scale back or cease our operations; we have a history of losses and may never be profitable; if we are unable to expand sales of our diagnostic tests in the United States, it would have a material adverse effect on our business and financial condition; the intensely competitive biotechnology market could diminish demand for our tests and products; the market may not be receptive to any diagnostic tests or therapeutic products using our microRNA technology; we currently have limited sales, marketing or distribution experience and may in the future depend significantly on third parties to commercialize microRNA-based diagnostic tests or therapeutic products we may develop; we are largely dependent upon our distributors for the success of commercialization of our current diagnostic tests; health insurers and other third-party payors may decide not to cover our diagnostic products or may provide inadequate reimbursement, which could jeopardize our commercial prospects; because of Medicare billing rules, we may not receive reimbursement for all tests provided to Medicare patients; if we fail to comply with our obligations under any licenses or related agreements, we could lose license rights that may be necessary for developing microRNA-based diagnostics and therapeutics; if we fail to comply with the complex federal, state, local and foreign laws and regulations that apply to our business, we could suffer severe consequences that could materially and adversely affect our operating results and financial condition; we contract with a single manufacturer for the purchase of microarray chips for certain tests, and the failure of this manufacturer to supply sufficient quantities on a timely basis could have a material adverse effect on our business; and other risk factors discussed under the heading "Risk Factors" in Rosetta's most recently filed Annual Report on Form 20-F, as filed with the SEC. In addition, any forward-looking statements represent Rosetta's views only as of the date of this release and should not be relied upon as representing its views as of any subsequent date. Rosetta does not assume any obligation to update any forward-looking statements unless required by law. RosettaGX Reveal™ Available in all 50 States PHILADELPHIA, PA and REHOVOT, ISRAEL / ACCESSWIRE / May 4, 2017 / Rosetta Genomics Ltd. (NASDAQ: ROSG), a genomic diagnostics company that improves treatment decisions by providing timely and accurate diagnostic information to physicians, announces it has received final approval for RosettaGX Reveal™ (Reveal), its novel microRNA classifier for the diagnosis of indeterminate thyroid cases from the New York State Department of Health (NYSDOH) under the Company's Molecular Oncology permit. RosettaGX Reveal is the only molecular test in the thyroid market that has been validated in a multicenter, international, blinded study using convenient, routinely prepared cytology slides. The Rosetta Laboratory is CLIA-certified, but New York State requires an additional license from the NYSDOH for Lab Developed Tests to be offered to patients in the state. The assay had previously received conditional approval and now that approval has become final. "We are very pleased to have final approval for this important cancer diagnostic for the benefit of physicians and patients in New York State. The NYSDOH has a very rigorous approval process and this final approval further confirms the overall robust performance of our Reveal assay," stated Kenneth A. Berlin, President and Chief Executive Officer of Rosetta Genomics. "Reveal is a truly differentiated assay being promoted in an established market that has substantial room for further penetration. Reveal's convenience and performance advantages are strongly resonating with clinicians, allowing us to continue to win business from the competition and to expand Reveal sales into untapped parts of the market. Continuing to have access for Reveal to the vast New York market will significantly enhance these efforts." "It is estimated that nearly 550,000 FNAs are performed on thyroid nodules each year in the U.S. and that approximately 740,000 are performed annually in Europe. Interpretation of FNA samples is not always straightforward, leading to an indeterminate result in up to 30% of the samples. Many patients with indeterminate results undergo surgery as a precaution despite the fact that up to 80% of these cases are benign. This exposes patients to unnecessary surgical risk and costs the healthcare system hundreds of millions of dollars. Through an analysis of our validation study data, we believe we can help prevent up to 75% of unnecessary thyroid surgeries," added Mr. Berlin. Rosetta is pioneering the field of molecular diagnostics by offering rapid and accurate diagnostic information that enables physicians to make more timely and informed treatment decisions to improve patient care. Rosetta has developed a portfolio of unique diagnostic solutions for oncologists, urologists, endocrinologists, cytopathologists and other specialists to help them deliver better care to their patients. RosettaGX Reveal™, a Thyroid microRNA Classifier for the diagnosis of cancer in thyroid nodules, as well as the full RosettaGX™ portfolio of cancer testing services are commercially available through the Company's Philadelphia, PA- and Lake Forest, CA-based CAP-accredited, CLIA-certified labs. Various statements in this release concerning Rosetta's future expectations, plans and prospects including, but not limited to statements relating to creating long term revenue opportunities via Reveal, achieving further market penetration and market acceptance from clinicians, expanding Reveal sales into untapped parts of the market, and growing global interest in this assay and statements containing the words "expect," "believe," "will," "may," "should," "project," "estimate," "anticipated," "scheduled," and like expressions, and the negative thereof, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various risks and uncertainties, including, but are not limited to the following: we will require substantial additional funds to continue our operations and, if additional funds are not available, we may need to significantly scale back or cease our operations; we have a history of losses and may never be profitable; if we are unable to expand sales of our diagnostic tests in the United States, it would have a material adverse effect on our business and financial condition; the intensely competitive biotechnology market could diminish demand for our tests and products; the market may not be receptive to any diagnostic tests or therapeutic products using our microRNA technology; we currently have limited sales, marketing or distribution experience and may in the future depend significantly on third parties to commercialize microRNA-based diagnostic tests or therapeutic products we may develop; we are largely dependent upon our distributors for the success of commercialization of our current diagnostic tests; health insurers and other third-party payors may decide not to cover our diagnostic products or may provide inadequate reimbursement, which could jeopardize our commercial prospects; because of Medicare billing rules, we may not receive reimbursement for all tests provided to Medicare patients; if we fail to comply with our obligations under any licenses or related agreements, we could lose license rights that may be necessary for developing microRNA-based diagnostics and therapeutics; if we fail to comply with the complex federal, state, local and foreign laws and regulations that apply to our business, we could suffer severe consequences that could materially and adversely affect our operating results and financial condition; we contract with a single manufacturer for the purchase of microarray chips for certain tests, and the failure of this manufacturer to supply sufficient quantities on a timely basis could have a material adverse effect on our business; and other risk factors discussed under the heading "Risk Factors" in Rosetta's most recently filed Annual Report on Form 20-F, as filed with the SEC. In addition, any forward-looking statements represent Rosetta's views only as of the date of this release and should not be relied upon as representing its views as of any subsequent date. Rosetta does not assume any obligation to update any forward-looking statements unless required by law.


News Article | December 15, 2016
Site: www.businesswire.com

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Synlogic, a privately-held biopharmaceutical company developing novel medicines based on its proprietary synthetic biology and microbiome platform, today announced the appointment of biotech industry veteran Samantha Truex as Chief Operating Officer (COO) and Head of Corporate Development. “We expect 2017 to be a pivotal year for Synlogic as we further demonstrate the breadth and power of our platform. Sam’s drug development background at both large and small biotechnology organizations will serve as a valuable asset to our team as we prepare to take our lead programs into the clinic,” said Jose Carlos Gutierrez-Ramos, Ph.D., CEO of Synlogic. “In addition, her deep experience leading corporate development efforts will serve us well as we seek to execute strategic partnerships that will fuel Synlogic’s growth into a fully-integrated biotechnology company focused on bringing a new class of drugs -- synthetic biotics -- to patients.” As COO and head of corporate development, Sam will be broadly responsible for developing and executing on a strategic plan that integrates internal programs and business development activities, including the development of financing strategies. In addition to strategic planning, corporate development and legal activities, Sam will also provide leadership for Synlogic’s corporate communications and alliance management activities. Sam comes to Synlogic with more than 20 years of industry experience, most recently from Padlock Therapeutics where she was integral to Padlock's operations and led the business development process culminating in its acquisition by Bristol-Myers Squibb earlier this year. Prior to Padlock, Sam spent several years each at Biogen and Genzyme. At Biogen, Sam served as vice president of corporate development, leading the negotiations for multiple licensing, collaboration and acquisition transactions and serving as program executive of FAMPYRA® during its launch phase and of ELOCTATE™ and ALPROLIX™ during the preclinical and early clinical phases. At Genzyme, Sam handled licensing and M&A transactions across multiple business units, including for Genzyme Molecular Oncology and Genzyme Genetics. Earlier in her career, Sam worked for Chiron Diagnostics and Health Advances. Sam earned a B.A. in biology from Dartmouth College, a B.E. in biomedical engineering from the Thayer School at Dartmouth and a MBA from the Tuck School at Dartmouth. Synlogic is a privately-held biopharmaceutical company based in Cambridge, Massachusetts, pioneering the development of a novel class of therapeutics, called synthetic biotics, based on its proprietary synthetic biology and microbiome platform. Synlogic’s two lead therapeutic programs are being developed for the potential treatment of rare inborn errors of metabolism of Urea Cycle Disorder (UCD) and Phenylketonuria (PKU). In addition to the company’s proprietary pipeline focused on rare diseases, the company is leveraging the broad potential of its synthetic biotics platform for novel drug development in major disease areas through partnerships with pharmaceutical and biotechnology companies. Synlogic is collaborating with AbbVie to develop synthetic biotics-based treatment for inflammatory bowel disease (IBD). Synlogic is backed by leading life sciences investors, including Atlas Venture, New Enterprise Associates (NEA), Orbimed, Deerfield and the Bill & Melinda Gates Foundation. For more information, please visit http://synlogictx.com/.


News Article | December 6, 2016
Site: www.eurekalert.org

DALLAS - Dec. 6, 2016 - Researchers at UT Southwestern Medical Center have found a new biomarker for glioma, a common type of brain cancer, that can help doctors determine how aggressive a cancer is and that could eventually help determine the best course of treatment. Researchers from the Harold C. Simmons Comprehensive Cancer Center found that high expression of a gene called SHOX2 predicted poor survival in intermediate grade gliomas. "As an independent biomarker, SHOX2 expression is as potent as the currently best and widely used marker known as IDH mutations," said Dr. Adi Gazdar, Professor of Pathology in the Nancy B. and Jake L. Hamon Center for Therapeutic Oncology and a member of the Simmons Cancer Center. According to the National Cancer Institute, cancers of the brain and nervous system affect nearly 24,000 people annually. In 2013, there were an estimated 152,751 people living with brain and other nervous system cancer in the United States. The overall 5-year survival rate is 33.8 percent. Knowing the probable survival status of an individual patient may help physicians choose the best treatment. In combination with IDH mutations or several other biomarkers, SHOX2 expression helped to identify subgroups of patients with a good prognosis even though other biomarkers had predicted a bad prognosis. "Our findings are based on analysis of previously published studies. They will have to be confirmed in prospective studies, and their clinical contribution and method of use remain to be determined," said Dr. Gazdar, who holds the W. Ray Wallace Distinguished Chair in Molecular Oncology Research. The findings are published in EBiomedicine. This work in brain cancer research is supported by the National Institutes of Health. Long-term goals of Dr. Gazdar's lab are to the determine molecular and genetic basis of human cancers, and to develop molecular insights to provide prognostic and diagnostic therapies in the treatment of human cancers. A former researcher at the National Cancer Institute, Dr. Gazdar's efforts there and at UT Southwestern have resulted in the collection and analysis of more than 2,500 human tumor specimens as well as the establishment of more than 400 lung, breast, ovary, and other types of tumor cell lines. Additional UT Southwestern researchers who contributed to the current study include Dr. Yu-An Zhang, Instructor in the Hamon Center for Therapeutic Oncology Research; Dr. Yunyun Zhou, Computational Biologist in the Department of Clinical Sciences; Dr. Xin Luo, Data Scientist in the Department of Bioinformatics; Dr. Luc Girard, Assistant Professor in the Hamon Center for Therapeutic Oncology Research; and Dr. Guanghua Xiao, Associate Professor in the Department of Clinical Sciences and a member of the Simmons Cancer Center. The Harold C. Simmons Comprehensive Cancer Center is the only NCI-designated Comprehensive Cancer Center in North Texas and one of just 47 NCI-designated Comprehensive Cancer Centers in the nation. Simmons Cancer Center includes 13 major cancer care programs. In addition, the Center's education and training programs support and develop the next generation of cancer researchers and clinicians. Simmons Cancer Center is among only 30 U.S. cancer research centers to be designated by the NCI as a National Clinical Trials Network Lead Academic Participating Site. Generally speaking, gliomas arise due to aberrations in normal brain cells. Depending on the nature of the aberration, the glioma can be fast- , intermediate- or slow-growing. Gliomas do not metastasize or travel to other parts of the body. Patients with gliomas commonly present with headaches, seizures, weakness, or vision changes. Decades ago, patients were treated with aggressive regimens that resulted in significant side effects without an improvement in the quantity or quality of life. Today, treatments for gliomas are much more sophisticated. Because scientists have a better understanding of the underlying biology and genetics of gliomas, physicians are able to tailor treatments to maximize effectiveness while minimizing unwanted side effects. UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution's faculty includes many distinguished members, including six who have been awarded Nobel Prizes since 1985. The faculty of almost 2,800 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in about 80 specialties to more than 100,000 hospitalized patients and oversee approximately 2.2 million outpatient visits a year. This news release is available on our website at http://www. . To automatically receive news releases from UT Southwestern via email, subscribe at http://www. .


News Article | October 11, 2016
Site: www.medicalnewstoday.com

Researchers at the University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute (UPCI) have demonstrated how Rad4, a protein involved in DNA repair, scans the DNA in a unique pattern of movement called 'constrained motion' to efficiently find structural faults in DNA. The findings, reported in the journal Molecular Cell, could lead to therapies that boost existing drug treatments and counter drug-resistance. "Rad4 is like the cop who is the first responder at an accident," said senior author Bennett Van Houten, Ph.D., Richard M. Cyert Professor of Molecular Oncology, Pitt School of Medicine, and co-leader of UPCI's Molecular and Cellular Cancer Biology Program. "The cop can move quickly to recognize where the incident is, and regulate traffic while directing the paramedics arriving in an ambulance." Constrained motion allows Rad4 to be fast enough to scan large lengths of DNA quickly, yet slow enough that it does not miss structural errors in DNA that could be caused by chemicals or ultraviolet (UV) light. Mutations in Rad4, called XPC in humans, and other proteins in the DNA repair machinery are known to cause a genetic condition called xeroderma pigmentosum, where individuals have sensitivity to sunlight and are at an extremely high risk for developing skin cancer. Muwen Kong, a graduate student in Dr. Van Houten's laboratory, along with his collaborators, tagged normal and mutant Rad4 molecules with light-emitting quantum dots. They then watched them move across strands of DNA suspended between beads using a fluorescence microscope. The results obtained suggest that the first responder, consisting of Rad4 and another protein, Rad23, quickly scans the DNA for accidents by attempting to bend it. Alterations in the structure of DNA, such as those caused by chemicals or UV light, change the ease with which DNA can be bent. Once a potential accident is recognized, the Rad4-Rad23 first-responder team slows down to a 'constrained motion' pattern to more carefully examine a smaller region of 500-1,000 base pairs in the DNA. When structural damage is confirmed, Rad4-Rad23 stays near the scene and flags down the 'paramedics,' comprised of the rest of the DNA repair machinery, to fix the damage. This mechanism, which Dr. Van Houten calls 'recognition-at-a-distance,' allows Rad4 to be near the error without impeding the rest of the DNA repair crew. Though much work is needed before these results can be translated to the clinic, the results provide new avenues to improve treatment methods, especially in cancer. Resistance is a major problem with current treatments, such as the drug cisplatin, which kills cancer cells by introducing DNA crosslinks similar to UV light. By developing drugs that target Rad4/XPC or other repair proteins, it could be possible to enhance the effects of current treatments when they are used together, and also reduce the chances of tumor cells developing resistance, Dr. Van Houten said. Co-investigators include Lili Liu Ph.D., Stefanie Böhm, Ph.D., Simon C. Watkins, Ph.D., and Kara A. Bernstein, Ph.D., all of the Pitt School of Medicine; Xuejing Chen, Ph.D., and Jung-Hyun Min, Ph.D., both of the University of Illinois at Chicago; Peng Mao, Ph.D., and John J. Wyrick, Ph.D., both of Washington State University; and Neil M. Kad, Ph.D., of the University of Kent, U.K. The research was funded by National Institutes of Health grants 5R01ES019566, 5R01ES024872, 5R01ES002614 and 2P30CA047904; and National Science Foundation grant MCB-1412692.


News Article | December 13, 2016
Site: www.eurekalert.org

Follicular lymphoma (FL), the second most common form of non-Hodgkin lymphoma, is a largely incurable disease of B cells, yet in many cases, because of its indolent nature, survival can extend to well beyond 10 years following diagnosis. Yet in a small number of cases, histological transformation - where fast-growing cells outnumber the smaller, slow-growing cells - or early progression to aggressive lymphoma occurs. The events leading to this increased and early mortality are poorly understood. In a study published in PLOS Medicine, Sohrab Shah and colleagues from the BC Cancer Agency in Vancouver, Canada, investigate the molecular events underlying transformation and progression and show that disparate evolutionary trajectories and mutational profiles drive these two distinct clinical endpoints. Using whole genome sequencing, the authors analyse the genome sequence of tumours and matched normal specimens from 41 patients and classify them according to their clinical endpoints: 1) patients who presented with transformation, 2) patients who experienced tumor progression within 2.5 years after starting treatment, without evidence of transformation, 3) and those who had neither transformation nor progression up to 5 years post-diagnosis. In addition, the authors use targeted capture sequencing of known follicular lymphoma associated genes in a larger cohort of 277 patients to investigate discrete genetic events that drive transformation and early progression. The authors show that tumors that progress early evolve in different ways than those that transform. Assessing mutations at two time points and following treatment they show that for tumours that transform, the cells or clones which constitute the majority of the aggressive tumour were extremely rare at diagnosis, if at all present. In contrast, for early progressive disease the clonal architecture remains similar from the time of diagnosis to relapse, indicating that the diagnostic tumour may already contain the properties that confer resistance to treatment. Analysis of the larger cohort pinpointed key genes and biological processes that were associated with transformation and progression. These findings provide a basis for future research on prognostic assay development and potential strategies for monitoring and treatment of patients with FL. This study was supported by a Program Project Grant from the Terry Fox Research Institute, Grant No. 1023) to SS, MM, RDG, CS and JC. We also wish to acknowledge generous long term funding support from the BC Cancer Foundation. SS is supported by a Canada Research Chair and a Michael Smith Foundation for Health Research, MSFHR scholar award. RK was supported by a Postdoctoral Trainee Fellowship Award from MSFHR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. I have read the journal's policy and the authors of this manuscript have the following competing interests: SPS is a founder and shareholder of Contextual Genomics Inc., developer of clinical genomic tests for cancer. Kridel R, Chan FC, Mottok A, Boyle M, Farinha P, Tan K, et al. (2016) Histological Transformation and Progression in Follicular Lymphoma: A Clonal Evolution Study. PLoS Med 13(12): e1002197. doi:10.1371/journal.pmed.1002197 Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver, British Columbia, Canada Bioinformatics Graduate Program, University of British Columbia, Vancouver, British Columbia, Canada Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia, Canada Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada Jewish General Hospital, Montreal, Quebec, Canada Translational Cell and Tissue Research Lab, Department for Imaging and Pathology, University of Leuven (KU Leuven), Leuven, Belgium Department of Pathology, Universitaire Ziekenhuizen Leuven (UZ Leuven), Leuven, Belgium Department of Laboratory and Pathology, Mayo Clinic, Rochester, Minnesota, United States of America Departments of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America IN YOUR COVERAGE PLEASE USE THIS URL TO PROVIDE ACCESS TO THE FREELY AVAILABLE PAPER:


News Article | November 3, 2016
Site: www.eurekalert.org

Combination therapy utilizing two approved immunotherapy drugs for cancer treatment may cause rare and sometimes fatal cardiac side effects linked to an unexpected immune response. In a study led by Vanderbilt University Medical Center (VUMC) investigators and published in the Nov. 3 issue of The New England Journal of Medicine, researchers describe two cases of acute and unexpected fatal myocarditis (inflammation of the heart muscle) that occurred in melanoma patients following treatment with a combination of ipilimumab and nivolumab. Both drugs are FDA-approved immune checkpoint inhibitors which stimulate an anti-tumor response in cancer patients. Ipilimumab is an anti-cytotoxic T-lymphocyte- associated antigen 4 (CTLA-4) antibody, and nivolumab, an anti-programmed death-1 (PD-1) antibody. The use of these immune checkpoint inhibitors, especially in combination using two such therapies, has enhanced the treatment of several types of malignancy. Common side effects of these agents such as inflammation of the skin, colon, liver, endocrine glands and lung, are thought to arise from off-target activation of T cells in the immune system. In the two study cases, a 65-year-old woman and a 63-year-old man, both with metastatic melanoma, were hospitalized nearly two weeks after initiation of the combination therapy. Javid Moslehi, M.D., assistant professor of Medicine, director of the Cardio-Oncology Program at VUMC and corresponding author of the study, said both patients had seemingly mild symptoms at the time of hospitalization. "The patients came with rather vague symptoms including fatigue and muscle aches. What made us take notice, however, were blood tests for cardiac damage that were extremely elevated and the electrocardiograms (EKG) that were abnormal in both cases. The problems quickly advanced such that the patients each needed a pacemaker to control the heart's electrical activity. The degree of cardiac arrhythmia was striking," Moslehi explained. "Even aggressive combinations of these immune therapies are usually well tolerated with very selective activity against the tumor instead of self," said study first author Douglas Johnson, M.D., M.S.C.I., assistant professor of Medicine and clinical director of Melanoma. "But we occasionally observe these cases of wildly dysregulated autoimmune activation." Johnson said VUMC physicians quickly treated the patients with high-dose corticosteroids (methylprednisolone). Despite aggressive treatment, both patients died from myocarditis. The two similar cases stimulated a cross-disciplinary effort at VUMC to investigate the mechanisms of toxicity and potential treatments for patients with such rare reactions. The investigators collaborated with colleagues at Harvard Medical School, Johns Hopkins School of Medicine, and Bristol-Myers Squibb, the company that makes both drugs. Justin Balko, Pharm.D., Ph.D., assistant professor of Medicine and Cancer Biology and leader of Molecular Oncology in the Center for Cancer Targeted Therapies at Vanderbilt-Ingram Cancer Center (VICC), said on autopsy and biopsy of the cardiac tissue it was clear that there was an immune reaction to the heart. VUMC pathologists found robust T cell and macrophage infiltrates. Importantly, there were shared populations of T cells infiltrating the myocardium which were identical to those present in tumor and skeletal muscle. "One hypothesis based on the data is that essentially the body is seeing the heart and muscle tissue as foreign, just like the tumor," Balko said. "This gives us a starting point to develop a model to see how consistent this is with other cases as they appear and once we have that model, determine the right way to intervene so that we can keep other patients safe." Study authors said global data reveal that myocarditis has occurred in less than one percent of patients treated with the ipilimumab/nivolumab combination therapy to date, suggesting this is a rare, potentially fatal T cell-driven drug reaction. Johnson suggested "presumably the treatment strategy would involve high-dose steroids and possibly other intensive immune-suppressive drugs, as well. The best regimen is unclear at this point." Other investigators on the study include Margaret Compton, Yaomin Xu, Mellissa Hicks, Matthew Alexander, Tyler Bloomer, Jason Becker, David Slosky, Elizabeth Phillips, Mark Pilkinton, Laura Craig-Owens, Robert Hoffman, and Dan Roden, VUMC; Igor Puzanov, VUMC and Roswell Park Cancer Institute, Buffalo, New York; Jeffrey Sosman, VUMC and Robert H. Lurie Comprehensive Cancer Center, Evanston, Illinois; Spyridon Chalkias, Igor Koralnik, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Joshua Gorham, Jonathan Seidman, Harvard Medical School, Boston; Benjamin Olenchock, Christine Seidman, Brigham and Women's Hospital, Boston; Janis Taube, Luis Diaz, Robert Anders, Johns Hopkins University School of Medicine, Baltimore, Maryland; Nina Kola, Gregory Plautz, Daniel Reshef, Jonathan Deutsch, Bristol-Myers Squibb, New York City; and Raquel Deering, Neon Therapeutics, Cambridge, Massachusetts. The authors have received funding from the Bready Family Foundation, NIH/NCI (6R00CA181491), VICC ambassadors, the VICC Breast Cancer Specialized Program of Research Excellence (SPORE) grant (P50 CA098131),and the National Comprehensive Cancer Network Young Investigator Award.


DALLAS--(BUSINESS WIRE)--The 2016 recipients of the Brinker Awards for Scientific Distinction will be recognized for their vital contributions to research today at the prestigious 39th annual San Antonio Breast Cancer Symposium (SABCS). Charles Perou, Ph.D. and Monica Morrow, M.D., FACS, will both deliver keynote lectures during the symposium, and will be honored at a reception this evening. Established by Komen in 1992, the Brinker Awards for Scientific Distinction recognize the efforts of pioneers in two critically important areas of the fight to end breast cancer: Clinical Research and Basic Science. This year’s winners join the ranks of an esteemed group of scientists who have been recognized for advancing breast cancer research and medicine with the Brinker Awards – the highest scientific honor awarded by Susan G. Komen, the world’s leading breast cancer organization. The 2016 Brinker Award for Scientific Distinction in Basic Science will be presented to Dr. Perou, the May Goldman Shaw Distinguished Professor of Molecular Oncology and Professor of Genetics and Pathology & Laboratory Medicine at the University of North Carolina School of Medicine and co-program leader of the breast cancer research program and member of the UNC Lineberger Comprehensive Cancer Center. Dr. Perou’s work has helped to characterize the diversity of breast tumors, demonstrating that breast cancers can be classified into at least five molecular subtypes. His work also led to the discovery of the basal-like/triple-negative breast cancer (TNBC) subtype. Further, he and his colleagues were among the first to discover that the breast cancer subtypes were of prognostic and predictive value, and to associate specific genetic mutations with specific breast cancer subtypes. Dr. Morrow, chief of the Breast Surgery Service and Anne Burnett Windfohr Chair of Clinical Oncology at Memorial Sloan Kettering Cancer Center and Professor of Surgery at Weill Cornell Medical College, will receive the Brinker Award for Scientific Distinction in Clinical Research. Dr. Morrow has been a champion of the idea that “more is not necessarily better” when it comes to breast cancer treatments, devoting her career to advancing clinical practice and empowering women to make treatment decisions. She was instrumental in showing that sentinel lymph node dissection is an effective and safe alternative to complete (axillary) lymph node dissection for many women with early metastatic breast cancer. More than 60 other Komen representatives including Scientific Advisory Board members, Komen Scholars and grantees will join Dr. Perou, Dr. Morrow and thousands of other leading physicians and researchers from around the globe at SABCS, contributing to discussions around experimental biology, etiology, prevention, diagnosis and therapy of breast cancer. Advancing breast cancer research has been a priority for Komen since opening its doors in 1982. To date, Komen has invested more than $920 million in breast cancer research, and is the largest nonprofit funder of breast cancer research outside of the U.S. government, currently funding nearly 300 research grants worldwide. Susan G. Komen is the world’s largest breast cancer organization outside of the federal government, funding more breast cancer research than any other nonprofit while providing real-time help to those facing the disease. Since its founding in 1982, Komen has funded more than $920 million in research and provided more than $2 billion in funding to screening, education, treatment and psychosocial support programs. Komen has worked in more than 60 countries worldwide. Komen was founded by Nancy G. Brinker, who promised her sister, Susan G. Komen, that she would end the disease that claimed Suzy’s life. Visit komen.org or call 1-877 GO KOMEN. Connect with us on social at ww5.komen.org/social.


News Article | February 15, 2017
Site: www.PR.com

The 2017 Women in Oncology Award Winners Honored by PRIMO Education The winners of the 2017 Women in Oncology Award were announced this morning at the 2nd Annual Practical Recommendations in Immuno and Molecular Oncology (PRIMO) Meeting. The Women in Oncology Awards are presented annually to three outstanding women in academia, industry, and advocacy, and seeks to recognize women who have made outstanding contributions to the lives of those fighting cancer. Wailea, HI, February 13, 2017 --( The Women in Oncology Awards are presented annually to three outstanding women in academia, industry, and advocacy, and seeks to recognize women who have made outstanding contributions to the lives of those fighting cancer. The 2017 the Women in Oncology Award Winners are: Academic Nancy Davidson, MD, is the Executive Director of the Fred Hutchinson and University of Washington Cancer Consortium, located in Seattle, WA. She is a world-renowned breast cancer researcher, who has dedicated her career to the study of cancer biology and treatment. In addition to her role at Fred Hutchinson, she is the President of the American Association for Cancer Research, and the Past-President of the American Society of Clinical Oncology. Advocacy Kathy Giusti is a Founder and Executive Chairman of the Multiple Myeloma Research Foundation (MMRF) and the Multiple Myeloma Research Consortium (MMRC), as well as the Faculty Co-Chair of the Harvard Business School Kraft Precision Medicine Accelerator. As Executive Chairman of the MMRF, she established innovative research models to accelerate the pace of development for lifesaving treatments, earning her recognition not only as a pioneer of precision medicine, but also as a strong advocate for patient engagement. Due to her and her foundation’s success, Ms. Giusti has earned numerous career accolades, including a #19 ranking in Fortune Magazine’s “World’s 50 Greatest Leaders”, and an appointment to President Obama’s 2015 Precision Medicine Initiative Working Group. Industry Jill DeSimone is the Head of US Oncology at Merck. Under her leadership, pembrolizumab received FDA approval in metastatic melanoma, non-small cell lung cancer, and head and neck squamous cell carcinoma, positively impacting a large number of patients across the US. Prior to her time at Merck, Ms. DeSimone was a Senior Vice President at Teva Pharmaceuticals, where she established the Global Women’s Health Unit, as well as a Senior Vice President at Bristol-Meyers Squibb. The organizers of this award, PRIMO Education and Cancer Expert Now, thank these three outstanding women for their commitment to the advancement of cancer care and advocacy, and look forward to their continuing contributions to oncology in the future. Wailea, HI, February 13, 2017 --( PR.com )-- The winners of the 2017 Women in Oncology Award were announced this weekend at the 2nd Annual Practical Recommendations in Immuno and Molecular Oncology (PRIMO) Meeting. The awards were Introduced by Charles Balch, MD, PhD(hc), of the MD Anderson Cancer Center, and presented by meeting Co-chairs Julie Brahmer, MD, MSc, of Johns Hopkins School of Medicine and Julie Vose, MD, MBA, of the University of Nebraska Medical Center.The Women in Oncology Awards are presented annually to three outstanding women in academia, industry, and advocacy, and seeks to recognize women who have made outstanding contributions to the lives of those fighting cancer. The 2017 the Women in Oncology Award Winners are:AcademicNancy Davidson, MD, is the Executive Director of the Fred Hutchinson and University of Washington Cancer Consortium, located in Seattle, WA. She is a world-renowned breast cancer researcher, who has dedicated her career to the study of cancer biology and treatment. In addition to her role at Fred Hutchinson, she is the President of the American Association for Cancer Research, and the Past-President of the American Society of Clinical Oncology.AdvocacyKathy Giusti is a Founder and Executive Chairman of the Multiple Myeloma Research Foundation (MMRF) and the Multiple Myeloma Research Consortium (MMRC), as well as the Faculty Co-Chair of the Harvard Business School Kraft Precision Medicine Accelerator. As Executive Chairman of the MMRF, she established innovative research models to accelerate the pace of development for lifesaving treatments, earning her recognition not only as a pioneer of precision medicine, but also as a strong advocate for patient engagement. Due to her and her foundation’s success, Ms. Giusti has earned numerous career accolades, including a #19 ranking in Fortune Magazine’s “World’s 50 Greatest Leaders”, and an appointment to President Obama’s 2015 Precision Medicine Initiative Working Group.IndustryJill DeSimone is the Head of US Oncology at Merck. Under her leadership, pembrolizumab received FDA approval in metastatic melanoma, non-small cell lung cancer, and head and neck squamous cell carcinoma, positively impacting a large number of patients across the US. Prior to her time at Merck, Ms. DeSimone was a Senior Vice President at Teva Pharmaceuticals, where she established the Global Women’s Health Unit, as well as a Senior Vice President at Bristol-Meyers Squibb.The organizers of this award, PRIMO Education and Cancer Expert Now, thank these three outstanding women for their commitment to the advancement of cancer care and advocacy, and look forward to their continuing contributions to oncology in the future.

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