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News Article | April 26, 2017
Site: www.sciencedaily.com

Patients who expressed the tumor antigen NY-ESO-1 had more aggressive cancers and were more likely to die early from their disease, according to a large study conducted by Roswell Park Cancer Institute researchers and published online ahead of print in the journal Gynecologic Oncology. "This is the largest study of NY-ESO-1 expression in ovarian cancer patients, and the first time that expression of this antigen has been identified as a marker for more aggressive disease," says the study's first author, J. Brian Szender, MD, MPH, Fellow in the Department of Gynecologic Oncology at Roswell Park. NY-ESO-1 is one of the few tumor antigens that have restricted expression in normal tissue but become aberrantly expressed in epithelial ovarian cancers and other solid tumors. From January 2002 to June 2016, more than 1,000 patients with ovarian cancer were tested at Roswell Park for NY-ESO-1 expression. Their median age at diagnosis was 61 years, and most patients were diagnosed with stage IIIC or stage IV disease. The research team found that NY-ESO-1 expression was associated with shorter duration of both progression-free survival (22 months versus 25 months) and overall survival (42 months versus 50 months). During the study period, the Roswell Park scientists enrolled a total of 68 ovarian cancer patients with NY-ESO-1-positive tumors to cancer vaccine trials targeting NY-ESO-1. The researchers found that patients with NY-ESO-1-expressing tumors who were enrolled in cancer vaccine trials had significantly improved overall survival compared to patients with NY-ESO-1 who did not participate in the cancer vaccine trials, and with patients without NY-ESO-1-expressing tumors. "We suggest that NY-ESO-1 be a high-priority target for future immunotherapy studies, given the high prevalence of NY-ESO-1 expression in ovarian cancer and the association of this tumor antigen with adverse clinical outcomes," says Kunle Odunsi, MD, PhD, FRCOG, Deputy Director of Roswell Park and Chair of the Department of Gynecologic Oncology. "It is possible that in the coming years, NY-ESO-1 expression in ovarian cancer will be as important to the treating oncologist as HER2 expression is for the treatment of breast cancer."


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

Pierian Biosciences, the premier developer of life science technologies providing treatment directing data to aid physicians in selecting the most appropriate therapy for their patients with cancer, has named Mark S. Gelder, MD, as chief medical officer. “We rely on Mark to ensure the delivery of quality diagnostic assays: the immune-proximity assay, CEER®, recently renamed PathwayINTELTM, and our drug response profiling assay, MiCK®, recently renamed ChemoINTELTM,” says Robert Henry, president and chief executive officer of Pierian Biosciences. “We’ll also be looking for Mark to help us maintain our industry presence and guide the development of collaborative agreements with partners such as academic centers, pharmaceutical companies and oncologists.” In addition, Gelder provides medical, clinical and scientific oversight as well as helping to define the company’s strategic direction. Dr. Gelder brings more than 25 years of oncology clinical trial and drug development experience to Pieiran. He is board certified in Internal Medicine, Obstetrics and Gynecology and Gynecologic Oncology. As an experienced researcher and clinician, he has significant regulatory experience working closely with the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) and in various leadership roles at pharmaceutical companies including Pfizer, Wyeth, Bayer, GE Healthcare, Heron Therapeutics and Inovio Pharmaceuticals. A graduate of the University of Virginia School of Medicine, Gelder received his residency training in internal medicine at University of Virginia and an additional residency in obstetrics and gynecology at the University of Alabama at Birmingham. While at UAB, Gelder also completed a fellowship in gynecologic oncology. He is currently a fellow of the American College of Obstetrics and Gynecology. Pierian’s PathwayINTEL is a functional proteomic profiling assay which provides quantitative information on the expression and activation status of proteins of interest to identify the true oncogenic “driver” and allow selection of the most appropriate targeted and/or biologic therapy for cancer patients. ChemoINTEL, the company’s functional drug response profiling assay, provides actionable information to guide selection on the effectiveness of cytotoxic agents to enhance clinical treatment decision-making. About Pierian Biosciences Based in Franklin, Tenn., Pierian Biosciences is a privately held life sciences and clinical pathology laboratory company offering treatment-directing diagnostic data to support more effective and lower cost cancer treatment. The company’s technology includes the ChemoINTEL and the PathwayINTEL Assay platforms. The company has laboratories in Franklin, Tenn. and San Diego, CA. For more information visit http://pierianbio.com.


News Article | October 28, 2016
Site: www.prweb.com

A total of 28 Mercy Medical Center physicians were recognized in Baltimore magazine’s November 2016 “Top Docs” issue, representing 23 separate specialties, ranging from breast cancer surgery to varicose veins. They are (as listed in the magazine): Dr. Kelly Alexander, General Surgery Dr. Mark Applefeld, Cardiology: Interventional Dr. Fermin Barrueto, Urogynecology Dr. John Campbell, Orthopedic Surgery: Foot & Ankle Dr. Bernard W. Chang, Plastic Surgery: Reconstructive and Plastic Surgery: Breast Dr. Teresa Diaz-Montes, Gynecologic Oncology Dr. Susan Dulkerian, Neonatology Dr. R. Mark Ellerkmann, Gynecology: General Dr. J. Lawrence Fitzpatrick, General Surgery Dr. Neil B. Friedman, Breast Surgery and Oncology: Breast Dr. Scott Huber, Gastroenterology Dr. Dwight D. Im, Gynecologic Oncology Dr. Maria Jacobs, Radiation Oncology Dr. Clifford Jeng, Orthopedic Surgery: Foot & Ankle Dr. Peter Ledakis, Oncology: General Dr. Paul Lucas, Surgery for Chronic Venous Disease/Varicose Veins Dr. Lynn Ludmer, Rheumatology Dr. David Maine, Pain Management Dr. Andrea Marx, Rheumatology Dr. Albert Polito, Pulmonary Dr. Neil B. Rosenshein, Gynecologic Oncology Dr. John Salkeld, Radiology: Nuclear Medicine Dr. Armando Sardi, Surgical Oncology Dr. David Sill, Interventional Radiology Dr. Amish Sura, Cardiology: Interventional Dr. Thomas Swope, General Surgery Dr. Debra Vachon, ColoRectal Dr. Linda C. Wang, Dermatology (Medical) Mercy’s Dr. Maria C.E. Jacobs, Director of Radiation Oncology, was among several doctors photographed and profiled for the special edition. Dr. Jacobs works in close collaboration with the cancer surgeons, including fellow Baltimore magazine “Top Doc” honoree, Dr. Neil B. Friedman, Director, The Hoffberger Breast Center to coordinate post surgical treatment for breast cancer patients. Dr. Jacobs and Dr. Friedman were the first team of doctors in the state of Maryland to use Intraoperative Radiotherapy (IORT), a state-of-the-art technology that allows patients to get treated in one single radiation therapy session – a notable advantage over the many multiple visits required prior to IORT. Each Mercy physician was recognized as among the best in their respective fields. Other honorees including Dr. Dwight Im, Dwight D. Im, M.D., FACOG, renowned gynecologic cancer surgeon and leader of Mercy Medical Center’s prestigious gynecology and robotic surgery programs, and been named a “Top Doctor" for 2016 earlier this year by Castle Connolly Medical Ltd.; Armando Sardi, M.D., FACS, respected and renowned Surgical Oncologist who has been honored as a Top Doc in Baltimore magazine multiple times, serves as Medical Director of The Institute for Cancer Care at Mercy and as Chief of Division of Surgical Oncology at Mercy and recognized internationally for his work in the field of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) to treat late stage, complex cancers of the abdominal region; and Teresa P. Diaz-Montes, M.D., MPH, FACOG, Associate Director of The Lya Segall Ovarian Cancer Institute, the first center in the region specifically designed for the treatment of ovarian cancer. Mercy Medical Center in Baltimore, MD, is a 142-year-old university affiliated medical facility named a "Top Hospital" by U.S. News and World Report with a national reputation for women's health care. For more information about Mercy, visit Mercy online at http://www.mdmercy.com; MDMercyMedia on FACEBOOK and TWITTER; or call 1-800-MD-MERCY.


News Article | December 16, 2016
Site: www.eurekalert.org

PHILADELPHIA - Delaying surgery after a diagnosis of uterine cancer can increase a women's risk of death, but operating too soon can be just as detrimental for some, Penn Medicine physicians report in a new study published in the American Journal of Obstetrics and Gynecology. In the study, women who had surgery (usually to remove the uterus) within the first two weeks after diagnosis had a significantly increased risk of death within five years, compared to those who had surgery three or four weeks after their initial diagnosis. The investigators examined more than 200,000 cases in the United States. Nearly two-thirds of the cases studied (140,078) were considered low-risk cancers. Of those, patients who had surgery in the first or second week after diagnosis had a 14 percent increased risk of death within five years compared to patients who had surgery in week three or four. For women with high-risk cancers (68,360), that number jumped to 20 percent. The risk, the authors suggest, is likely rooted in the delivery of care, rather than the cancer itself. In both risk groups, patients undergoing early surgery were more likely to die within 30 days of their operation. These patients were also more likely to be black, have advanced stage disease, have no insurance or be on Medicaid, and receive care at low-volume hospitals. "We suspect that physicians diagnosing endometrial cancer may believe, not unreasonably, that the best thing they can do for those patients is to operate as soon as possible, because if they wait too long the cancer could progress, resulting in a worse outcome," said senior author David I. Shalowitz, MD, a fellow in Gynecologic Oncology at the Perelman School of Medicine at the University of Pennsylvania. "But, the results of our study suggest that pre-surgical care and referring patients to a gynecologic oncologist may be more important." This year, over 60,000 women in the United States will be diagnosed with endometrial cancer, or cancer of the lining of the uterus. That number is expected to grow as obesity rates rise, since being obese increases a woman's risk of endometrial cancer, according to the National Cancer Institute. Endometrial cancer generally occurs in post-menopausal women over 50. In many cases, cancer-related symptoms such as abnormal menstruation send women to the doctor, allowing care providers to diagnose the condition early. Overall, the five-year survival rate is 82 percent. Researchers also observed higher mortality rates in women with low-risk cancers whose surgery took place eight weeks or more after diagnosis. Long wait times have been associated with poorer survival outcomes in breast, rectal and bladder cancers; however, past studies of endometrial cancer have produced mixed findings. Factors such as poor access to care, insurance status, and pre-existing conditions like heart disease, could delay surgeries. Five-year survival rates worsened as time-to-surgery increased, the study found: from 84.5 percent at eight weeks to 82.1 percent at week 11, to 78.6 percent at week 15, for example. There was no increased risk of death for women with high-risk cancers who had surgery after the third week, suggesting that for these women, the type and extent of disease at diagnosis contributes more to survival outcomes than progression of disease during the wait for surgery, the authors said. The team recommends that the target interval between diagnosis and treatment be less than eight weeks, especially for women with low-risk cancers. They also call on gynecologic oncologists and policy makers to make use of these findings to help develop national practice standards for uterine cancer care delivery. "Knowledge is power," Shalowitz said. "The primary goal is to make sure that there is a mechanism in place so that women who have a cancer diagnosis can see a specialist in the appropriate time period, that they are able to physically get to a high-volume treatment center, and that the process of referral and medical optimization for surgery can be done expediently." Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania(founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $5.3 billion enterprise. The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 18 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $373 million awarded in the 2015 fiscal year. The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine. Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2015, Penn Medicine provided $253.3 million to benefit our community.


News Article | October 31, 2016
Site: globenewswire.com

WALTHAM, Mass., Oct. 31, 2016 (GLOBE NEWSWIRE) -- TESARO, Inc. (NASDAQ:TSRO), an oncology-focused biopharmaceutical company, today announced the presentation of data from the ENGOT-OV16/NOVA trial of niraparib at the 2016 International Gynecologic Cancer Society (IGCS) Biennial Meeting in Lisbon, Portugal. These data were presented on Sunday, October 30 during the Best Oral session by Dr. Ursula Matulonis, M.D., Medical Director of the Gynecologic Oncology Program at Dana-Farber Cancer Institute and principal investigator on the ENGOT-OV16/NOVA trial, during the Best Oral session. The results were previously published in the New England Journal of Medicine on October 8, 2016 and presented at the ESMO 2016 Congress. “Many women with recurrent ovarian cancer experience a fear of recurrence in between regimens of platinum-based chemotherapy. The availability of an oral maintenance treatment that could lengthen the progression free survival interval between rounds of platinum-based chemotherapy with a tolerable side effect profile could be very empowering for patients,” said Dr. Matulonis. “The data from ENGOT-OV16/NOVA are extremely encouraging and demonstrate the potential of niraparib to offer a meaningful benefit for our patients with ovarian cancer.” “We are grateful for the patients, their families, and the caregivers that participated in the ENGOT-OV16/NOVA study, and we would like to thank our partners at ENGOT for their diligence in executing this trial,” said Mary Lynne Hedley, Ph.D., President and COO of TESARO. “We believe the results of this Phase 3 study demonstrated a meaningful benefit for women with platinum sensitive, recurrent ovarian cancer. We are pleased that the EMA recently accepted for review the MAA for niraparib, and we are on track to complete the rolling NDA submission imminently.” ENGOT-OV16/NOVA is a double-blind, placebo-controlled, international Phase 3 trial of niraparib that enrolled 553 patients with recurrent ovarian cancer who were in response to their most recent platinum-based chemotherapy. This trial was designed to assess progression free survival (PFS) in a broad population of patients who were assigned to one of two cohorts based upon germline BRCA mutation status. The ENGOT-OV16/NOVA trial successfully achieved its primary endpoint in both cohorts, demonstrating that niraparib treatment significantly prolonged PFS compared to control in patients who were germline BRCA mutation (gBRCAmut) carriers and in patients who were not germline BRCA mutation (non-gBRCAmut) carriers. A high proportion of patients in both treatment groups in both cohorts had received three or more prior lines of chemotherapy. The most common (≥10%) treatment-emergent grade 3/4 adverse events in the niraparib arm were thrombocytopenia (33.8%), anemia (25.3%), and neutropenia (19.6%) with treatment discontinuation for these events of 3.3%, 1.4% and 1.9%, respectively. Thrombocytopenia was not associated with grade 3/4 bleeding events. The majority of these hematological laboratory abnormalities occurred within the first three cycles; following dose modifications the incidence of these lab abnormalities decreased and thrombocytopenia and neutropenia were infrequent beyond cycle 3. The rates of MDS/AML in the niraparib (1.4%) and control (1.1%) arms were similar. There were no deaths among patients during study treatment. About the Phase 3 ENGOT-OV16/NOVA Clinical Trial of Niraparib ENGOT-OV16/NOVA is a double-blind, placebo-controlled, international Phase 3 trial of niraparib that enrolled 553 patients with recurrent ovarian cancer who were in a response to their most recent platinum-based chemotherapy. Patients were enrolled into one of two independent cohorts based on germline BRCA mutation status. One cohort enrolled patients who were germline BRCA mutation carriers (gBRCAmut), and the second cohort enrolled patients who were not germline BRCA mutation carriers (non-gBRCAmut) and included patients with HRD-positive and HRD-negative tumors. Within each cohort, patients were randomized 2:1 to receive niraparib or placebo and were treated continuously with placebo or 300 milligrams of niraparib, dosed as three 100 milligram tablets once per day, until progression. The primary endpoint of this study was progression-free survival (PFS). Secondary endpoints include patient-reported outcomes, chemotherapy-free interval length, PFS 2, overall survival, and other measures of safety and tolerability.  More information about this trial is available at http://clinicaltrials.gov/show/NCT01847274. About Niraparib Niraparib is an oral, once-daily PARP inhibitor that is currently being evaluated in four ongoing pivotal trials. TESARO is building a robust niraparib franchise by assessing activity across multiple tumor types and by evaluating several potential combinations of niraparib with other therapeutics. The ongoing development program for niraparib includes a Phase 3 trial in patients with platinum-sensitive, recurrent ovarian cancer (the NOVA trial); a Phase 3 trial in patients with first-line ovarian cancer (the PRIMA trial); a registrational Phase 2 treatment trial in patients with ovarian cancer (the QUADRA trial); and a Phase 3 trial for the treatment of patients with BRCA-mutant breast cancer (the BRAVO trial). Several combination studies are also underway, including trials of niraparib plus pembrolizumab and niraparib plus bevacizumab. Janssen Biotech has licensed rights to develop and commercialize niraparib specifically for patients with prostate cancer worldwide, except in Japan. The U.S. Food and Drug Administration (FDA) has granted Fast Track designation to niraparib for the treatment of patients with recurrent platinum-sensitive ovarian, fallopian tube, or primary peritoneal cancer. TESARO has initiated a rolling submission of a New Drug Application (NDA) for niraparib to the FDA, and intends to complete this submission during the fourth quarter. The Marketing Authorization Application (MAA) for niraparib has been submitted to and accepted for review by the European Medicines Agency (EMA) for the maintenance treatment of patients with platinum-sensitive, recurrent ovarian cancer who are in response to platinum-based chemotherapy. Niraparib is an investigational agent and, as such, has not been approved by the U.S. FDA, the European Medicines Agency (EMA), or any other regulatory agencies. About Ovarian Cancer Approximately 22,000 women are diagnosed each year with ovarian cancer in the United States, and more than 65,000 women are diagnosed annually in Europe. Ovarian cancer is the fifth most frequent cause of cancer death among women. Despite high response rates to platinum-based chemotherapy in the second-line advanced treatment setting, approximately 85% of patients will experience recurrence within two years. If approved, niraparib may address the difficult “watchful waiting” periods experienced by patients with recurrent ovarian cancer in between cycles of platinum-based chemotherapy. About TESARO TESARO is an oncology-focused biopharmaceutical company dedicated to improving the lives of cancer patients by acquiring, developing and commercializing safer and more effective therapeutics. For more information, visit www.tesarobio.com. To the extent that statements contained in this press release are not descriptions of historical facts regarding TESARO, they are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Words such as "may," "will," "expect," "anticipate," "estimate," "intend," and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. Forward-looking statements in this release involve substantial risks and uncertainties that could cause our clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainties inherent in expectations with respect to regulatory submissions and approvals, and other matters that could affect the availability or commercial potential of our drug candidates. TESARO undertakes no obligation to update or revise any forward-looking statements. TESARO undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of the Company in general, see TESARO's Annual Report on Form 10-K for the year ended December 31, 2015, and its Quarterly Report on Form 10-Q for the quarter ended June 30, 2016.


News Article | November 28, 2016
Site: www.prweb.com

A new clinical study underway at Roswell Park Cancer Institute is the first to test the combination of the immunotherapy pembrolizumab with two other drugs as treatment for recurrent epithelial ovarian cancer, and is also the first ovarian cancer clinical trial to incorporate analysis of patients’ microbiomes — the bacteria present in the human gut and other organs. This new study, led by Principal Investigator Emese Zsiros, MD, PhD, FACOG, Assistant Professor of Oncology in Roswell Park’s Department of Gynecologic Oncology and Center for Immunotherapy, is a phase II clinical trial that will enroll approximately 40 patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, and will evaluate the impact of the combination of the PD1-targeting antibody pembrolizumab (Keytruda) with intravenous bevacizumab (Avastin) and oral cyclophosphamide (Cytoxan) on antitumor immune responses and on progression-free survival. Pembrolizumab has been approved by the U.S. Food and Drug Administration for treatment of advanced melanoma, some metastatic non-small cell lung cancers and recurrent squamous cell head/neck carcinoma, but has only been tested in a small number of ovarian cancer patients, as a single drug and showing modest response. The investigators say a strong scientific rationale supports their hypothesis that the combination of pembrolizumab with two other drugs that have already been approved to treat ovarian cancer — bevacizumab and low-dose oral cyclophosphamide — may have much broader benefit for patients. “Our biggest hope is that by trying these three drugs in combination, we can significantly extend the lives of patients with recurrent ovarian cancer. We also hope to minimize the side effects associated with chemotherapy drugs, and to markedly improve the quality of our patients’ lives,” says Dr. Zsiros. “We will be looking at potential biomarkers that will tell us who can most benefit from this therapy combination and to better understand how cancer cells and immune cells communicate with one another so that we can design better medications to kill cancer efficiently.“ As part of this study, the clinical team will analyze blood, tumor, stool, vaginal and skin microbiome samples, looking to identify possible associations between these markers with clinical outcomes and tumor response. The study, which is supported by a grant from Merck & Co. Inc., maker of pembrolizumab, will be one of the first to analyze these bacteria to determine possible associations with response to immunotherapeutic agents in patients with cancer. “We’re looking at how to improve our immune defenses to cancer, but we’re looking at it from a variety of angles,” says Dr. Zsiros. “There’s a whole new area of research suggesting that what’s going on in our gut, our gut flora, has a huge influence on your overall health and happiness, and this study will extend that work into some new directions.” According to the National Cancer Institute, epithelial ovarian cancer is one of the most common gynecologic malignancies, and is the fifth most frequent cause of cancer death in women. To learn more about the clinical research study, call 1-877-ASK-RPCI (1-877-275-7724) or send an e-mail to ASKRPCI(at)roswellpark(dot)org. Additional details are available at ClinicalTrials.gov. For an online version of this release, please visit: https://www.roswellpark.org/media/news/new-ovarian-cancer-immunotherapy-study-poses-question-can-microbiome-influence-treatment Editor’s note: See a video interview with Emese Zsiros, MD, PhD, FACOG, Principal Investigator of the new study, at https://youtu.be/q-Fi-yxQPNE. The mission of Roswell Park Cancer Institute (RPCI) is to understand, prevent and cure cancer. Founded in 1898, RPCI is one of the first cancer centers in the country to be named a National Cancer Institute-designated comprehensive cancer center and remains the only facility with this designation in Upstate New York. The Institute is a member of the prestigious National Comprehensive Cancer Network, an alliance of the nation’s leading cancer centers; maintains affiliate sites; and is a partner in national and international collaborative programs. For more information, visit http://www.roswellpark.org, call 1-877-ASK-RPCI (1-877-275-7724) or email askrpci(at)roswellpark(dot)org. Follow Roswell Park on Facebook and Twitter.


News Article | February 15, 2017
Site: www.eurekalert.org

A team of 18 University of California San Diego School of Medicine and Moores Cancer Center researchers has developed a new tool to analyze an often overlooked aspect of cancer genetics -- an alteration that results in the loss or gain in a copy of a gene. This change, known as somatic copy-number alterations, may be key to disease progression and might offer new therapeutic approaches for ovarian cancer and other malignancies. "When most people think about cancer genetics, they think about single key mutations that foster tumor formation -- very specific things like the BRCA genes," said Joe R. Delaney, PhD, a fellow in the Clinical Translation program at UC San Diego Moores Cancer Center and lead author of the paper published February 15 in Nature Communications. "These changes are often referred to as tumor drivers but these are not the only deviations that impact cancer growth. We explored other possibilities." More than 90 percent of genetic changes in cancer cells involve the loss or gain of a single copy of a gene, rather than a mutation. A tumor cell might have one copy or three instead of the normal two copies -- one provided by each parent. This area has not been explored in depth, since experience with other diseases has taught scientists that the loss of one gene copy might not lead to disease symptoms because the second copy provided by the other parent fills in. Delaney and team wondered if this were true if several single gene copies that cooperated for the same cellular function were lost, and what the patterns might be in different cancers. The team designed the Haploinsufficient/Triplosensitive Gene (HAPTRIG) computational tool to identify pathways significantly disrupted by the loss and gain of genes. Ovarian cancer in particular is fraught with these alterations -- with more than 60 percent of genes affected. When the team analyzed this malignancy using HAPTRIG, the pathway that stood out was autophagy -- a natural process of cell death that helps maintain normal cellular health. Ovarian cancer cells use autophagy all of the time, but also lose several copies of autophagy genes resulting in a compromised capacity. The researchers then used a combination of existing United States Food and Drug Administration-approved drugs to target autophagy and found ovarian cancer cells to be highly sensitive to these drugs in several different mouse cancer models -- even among cells resistant to standard chemotherapy. The combination of drugs appeared less toxic than standard chemotherapy, were relatively inexpensive and should be clinically evaluated, said Dwayne G. Stupack, PhD, the study's senior author and associate professor in the dDivision of Gynecologic Oncology at Moores Cancer Center. With further work, said the authors, this finding could lead to new approaches to treat chemotherapy-resistant disease, and could enhance treatment of other cancers as well. "Our study suggests that a roadmap of targetable genetic changes in tumors should not be limited to mutations," said Stupack. "HAPTRIG may reveal additional targetable pathways across cancer types. We have provided a free web-tool to allow the community to easily perform a HAPTRIG analysis on 21 cancer types."


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

A team of 18 University of California San Diego School of Medicine and Moores Cancer Center researchers has developed a new tool to analyze an often overlooked aspect of cancer genetics -- an alteration that results in the loss or gain in a copy of a gene. This change, known as somatic copy-number alterations, may be key to disease progression and might offer new therapeutic approaches for ovarian cancer and other malignancies. "When most people think about cancer genetics, they think about single key mutations that foster tumor formation -- very specific things like the BRCA genes," said Joe R. Delaney, PhD, a fellow in the Clinical Translation program at UC San Diego Moores Cancer Center and lead author of the paper published February 15 in Nature Communications. "These changes are often referred to as tumor drivers but these are not the only deviations that impact cancer growth. We explored other possibilities." More than 90 percent of genetic changes in cancer cells involve the loss or gain of a single copy of a gene, rather than a mutation. A tumor cell might have one copy or three instead of the normal two copies -- one provided by each parent. This area has not been explored in depth, since experience with other diseases has taught scientists that the loss of one gene copy might not lead to disease symptoms because the second copy provided by the other parent fills in. Delaney and team wondered if this were true if several single gene copies that cooperated for the same cellular function were lost, and what the patterns might be in different cancers. The team designed the Haploinsufficient/Triplosensitive Gene (HAPTRIG) computational tool to identify pathways significantly disrupted by the loss and gain of genes. Ovarian cancer in particular is fraught with these alterations -- with more than 60 percent of genes affected. When the team analyzed this malignancy using HAPTRIG, the pathway that stood out was autophagy -- a natural process of cell death that helps maintain normal cellular health. Ovarian cancer cells use autophagy all of the time, but also lose several copies of autophagy genes resulting in a compromised capacity. The researchers then used a combination of existing United States Food and Drug Administration-approved drugs to target autophagy and found ovarian cancer cells to be highly sensitive to these drugs in several different mouse cancer models -- even among cells resistant to standard chemotherapy. The combination of drugs appeared less toxic than standard chemotherapy, were relatively inexpensive and should be clinically evaluated, said Dwayne G. Stupack, PhD, the study's senior author and associate professor in the dDivision of Gynecologic Oncology at Moores Cancer Center. With further work, said the authors, this finding could lead to new approaches to treat chemotherapy-resistant disease, and could enhance treatment of other cancers as well. "Our study suggests that a roadmap of targetable genetic changes in tumors should not be limited to mutations," said Stupack. "HAPTRIG may reveal additional targetable pathways across cancer types. We have provided a free web-tool to allow the community to easily perform a HAPTRIG analysis on 21 cancer types."


News Article | October 31, 2016
Site: www.eurekalert.org

Standard-of-care treatment for locally advanced cervical cancer includes radiation, chemotherapy and brachytherapy (in which radiation is implanted internally). A University of Colorado Cancer Center study published in the journal Gynecologic Oncology shows that only 44 percent of patients in a large, national sample received all three components of this accepted, best treatment. Patients who received standard-of-care (SOC) lived longer than women who received any combination of two components of SOC. The major difference in treatments received and overall survival was the presence or absence of brachytherapy. "Unfortunately, not all women have access to a center that offers this technique," says Christine Fisher, MD, MPH, CU Cancer Center investigator and board certified radiation oncologist. Fisher's collaborators included first author Tyler Robin, MD, PhD, resident in the CU School of Medicine Department of Radiation Oncology with growing expertise in women's cancers. The study, which used the data of 15,194 cervical cancer patients from the National Cancer Database, also found that women with low socioeconomic status or who were African American were even less likely to receive SOC. Patients treated at high-volume centers, academic centers, comprehensive community cancer centers, and those who were higher in socioeconomic status or had private insurance were more likely to receive all three components of SOC. "A lot of this has to do with the fact that brachytherapy requires equipment and expertise," Fisher says. "And there's no substitute for it. We see some patients whose care is managed in less specialized settings coming to University of Colorado just for the brachytherapy component of their treatment. Others simply miss out on this important piece of their care." In fact, brachytherapy has been used for more than a century, having been pioneered independently by Pierre Curie and Alexander Graham Bell in the early 20th century. Modern advances in image guidance have made the technique safe in terms of radiation exposure for both physician and patient. "We have a couple take-home messages," says Fisher. "First is that virtually all of these cervical cancers are preventable with vaccination against the HPV virus and by screening, which can catch the precursors of cervical cancer before the development of the disease itself. By far, the best solution is prevention. Then if a woman does develop cervical cancer, she should look for a center that offers brachytherapy. It's critically important."


PRINCETON, N.J., Nov. 11, 2016 (GLOBE NEWSWIRE) -- Advaxis, Inc. (NASDAQ:ADXS), a clinical stage biotechnology company developing cancer immunotherapies, announced new data highlighting the potential therapeutic benefit of Advaxis’ lead immunotherapy candidate, axalimogene filolisbac (AXAL), both as a monotherapy and in combination with antibody-based immunotherapies in multiple patient populations with HPV+ cancers.  These data will be presented at the Society for Immunotherapy of Cancer (SITC) Annual Meeting & Associated Programs this week in National Harbor, MD. This Phase 1 (Part A; 3+3) dose-escalation study was designed to assess the overall safety and select the recommended phase 2 dose (RP2D) of AXAL in combination with durvalumab in patients with recurrent/metastatic cervical or HPV+ HNSCC cancer.  Patients received AXAL (1×109 colony-forming units [CFU]) every four weeks and durvalumab (3 mg/kg or 10 mg/kg) every two weeks. Preliminary results from Part A dose escalation showed that there were no dose limiting toxicities observed, and the safety profile was consistent with previous findings for both AXAL and durvalumab. The recommended phase 2 dose was established as 1×109 CFU for AXAL and 10 mg/kg for durvalumab. One patient with cervical cancer achieved a complete response, which remains ongoing after 12 months of follow-up, and one patient, also with cervical cancer, achieved a partial response with subsequent disease progression. In addition, two patients with HNSCC achieved stable disease.  Treatment related adverse events (TRAE) were reported in 91 percent of patients; the majority were either grade 1 or grade 2 events such as chills, fever, nausea and hypotension. Grade 3 TRAEs occurred in three patients, and one patient experienced a grade 4 event. “When treating or evaluating investigational therapies for these kinds of metastatic, recurrent tumors, it is rare for an immunotherapy to result in a complete response,” said Brian Slomovitz, MD, principal investigator and Director of the Division of Gynecologic Oncology in the Department of Obstetrics and Gynecology at the University of Miami Miller School of Medicine. “These early data show encouraging anti-tumor activity of the combination of AXAL and durvalumab and the regimen was generally well tolerated, which supports continued study of this combination regimen.” A preclinical study evaluated the ability of AXAL to control tumor growth, prolong survival and reprogram the tumor microenvironment in combination with agonistic antibodies of T cell co-stimulatory receptors or with antagonistic antibodies of immune checkpoint inhibitors in an HPV+ tumor model.  Of the monoclonal antibodies (mAbs) tested, anti-CD137 mAb and anti-CTLA-4 mAb were the most effective at synergizing with AXAL to eradicate established HPV+ tumors and to provide long-term survival (>8 weeks).  Complete tumor regression was observed in 28 percent of the AXAL + anti-CD137 mAb treatment group and in 33 percent of the AXAL + anti-CTLA-4 mAb treatment group. The study demonstrated a reprogramming of the tumor microenvironment in favor of antitumor immunity in both of the combination treatment groups. Importantly, there were increased percentages of tumor antigen-specific T cells and mature dendritic cells as well as decreased percentages of regulatory T cells and immunosuppressive macrophages compared to the single-agent treatments. Together, these data show that AXAL in combination with a CD137 agonistic antibody or with a CTLA-4 antagonistic antibody synergize to enhance antitumor immunity. Advaxis’ Phase 3 AIM2CERV trial is a double-blind, placebo-controlled, multinational, multicenter, randomized study (NCT02853604). AIM2CERV is designed to demonstrate the efficacy and safety of AXAL as an adjuvant treatment in patients with stage I-IVA high risk, locally-advanced cervical cancer who have received cisplatin-based concurrent chemoradiation therapy (CCRT).  Following CCRT, patients will receive AXAL for up to one year. A disease-free survival analysis will be conducted following at least 184 events. The study will enroll approximately 450 patients at 150 sites.  Several trial sites are currently open and actively screening patients. In July, Advaxis received a Special Protocol Assessment for the AIM2CERV trial, as well as Fast Track designation for AXAL as an adjuvant therapy for HRLACC patients.  For more information on Advaxis clinical trials, visit www.clinicaltrials.gov. The presentation slides and audio are now available at www.advaxis.com. Located in Princeton, N.J., Advaxis, Inc. is a clinical-stage biotechnology company developing multiple cancer immunotherapies based on its proprietary Lm Technology™. The Lm Technology, using bioengineered live attenuated Listeria monocytogenes (Lm) bacteria, is the only known cancer immunotherapy agent shown in preclinical studies to both generate cancer fighting T cells directed against cancer antigens and neutralize Tregs and myeloid-derived suppressor cells (MDSCs) that protect the tumor microenvironment from immunologic attack and contribute to tumor growth. Advaxis' lead Lm Technology immunotherapy, AXAL, targets human papillomavirus (HPV)-associated cancers and is in clinical trials for three potential indications: Phase 3 in invasive cervical cancer, Phase 2 in head and neck cancer, and Phase 2 in anal cancer. The FDA has granted AXAL orphan drug designation for each of these three clinical settings, as well as Fast Track designation for adjuvant therapy for HRLACC patients and a Special Protocol Assessment for the Phase 3 AIM2CERV trial in HRLACC patients. AXAL has also been classified as an advanced therapy medicinal product for the treatment of cervical cancer by the European Medicines Agency's Committee for Advanced Therapies. Advaxis has two additional immunotherapy products: ADXS-PSA in prostate cancer and ADXS-HER2 in HER2 expressing solid tumors, in human clinical development. In addition, Advaxis and Amgen are developing ADXS-NEO, a preclinical investigational cancer immunotherapy treatment designed to activate a patient's immune system to respond against the unique mutations, or neoepitopes, contained in and identified from each individual patient's tumor, with plans to enter the clinic in 2017. For additional information on Advaxis, visit http://www.advaxis.com/ and connect on Twitter, LinkedIn, Facebook, YouTube and Google+. This press release contains forward-looking statements, including, but not limited to: statements regarding the completion and timing of the offering of shares. These forward-looking statements are subject to a number of risks, including the risk factors set forth from time to time in Advaxis’ SEC filings, including but not limited to its report on Form 10-K for the fiscal year ended October 31, 2015, which is available at http://www.sec.gov, as well as the risks identified or incorporated by reference in the registration statement and the prospectus supplement relating to the offering. Advaxis undertakes no obligation to publicly release the result of any revision to these forward-looking statements, which may be made to reflect the events or circumstances after the date hereof or to reflect the occurrence of unanticipated events, except as required by law. You are cautioned not to place undue reliance on any forward-looking statements.

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