Author Interviews, Biomarkers, Cancer Research, Genetic Research, Ovarian Cancer / 07.08.2023

MedicalResearch.com Interview with: Pei Wang, PhD Professor, Department of Genetics and Genomic Sciences Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA Michael J. Birrer MD PhD Director, Winthrop P. Rockefeller Cancer Institute University of Arkansas for Medical Sciences Little Rock, AR 72205 Amanda G. Paulovich MD PhD Translational Science and Therapeutics Division Fred Hutchinson Cancer Center Seattle WA 98109 MedicalResearch.com: What is the background for this study? How common is serous ovarian cancer? Response: Epithelial ovarian cancer accounts for >185,000 deaths/year worldwide. The most common subtype, high-grade serous ovarian cancer (HGSOC), accounts for 60% of deaths. Despite improvements in surgical and chemotherapeutic approaches, HGSOC mortality has not changed in decades. Five-year survival remains ~30% for the majority of patients. Standard of care involves surgical debulking combined with adjuvant or neoadjuvant chemotherapy with carbo- or cisplatin in combination with a taxane. At diagnosis, HGSOC is among the most chemo-sensitive of all epithelial malignancies, with initial response rates of ~85%, presumably related to DNA repair defects. Platinum is thought primarily to drive the response rate, due to the lower single-agent response rate for taxanes. Unfortunately, 10-20% of HGSOC patients have treatment-refractory disease at diagnosis, fail to respond to initial chemotherapy, and have a dismal prognosis. The poor response to subsequent therapy and median overall survival of ~12 months for these patients has not changed in 40 years. Despite >30 years of literature studying platinum resistance in cancer, there currently is no way to distinguish refractory from sensitive HGSOCs prior to therapy. Consequently, patients with refractory disease experience the toxicity of platinum-based chemotherapy without benefit. Due to their rapid progression, they are commonly excluded from participating in clinical trials. Consequently, there is no ongoing clinical research that could identify effective therapeutic agents for these patients or provide insights into molecular mechanisms of refractory disease.  “Right now, we can’t identify drug-resistant ovarian cancer patients up front,” said co-senior author Michael Birrer, MD, PhD, who directs UAMS’ Winthrop J. Rockefeller Cancer Institute. “We find them by default: They get sick and pass away so quickly that they can’t even be put on new clinical trials.” To address this unmet clinical need, we performed proteogenomic analysis of treatment-naïve HGSOCs (chemo-sensitive and chemo-refractory) to identify molecular signatures of refractory HGSOC and to identify potential treatment targets. (more…)
Author Interviews, JAMA, Ovarian Cancer / 04.08.2023

MedicalResearch.com Interview with: Zai LabRafael Amado, M.D. President, head of Global Oncology Research and Development Zai Lab MedicalResearch.com: What is the background for this study? Response: Zai lab is focused on discovering and developing innovative therapies that will help address medical conditions where there are serious unmet needs. Advanced ovarian cancer, with a low survival and high recurrence rate, is a key focus of our oncology R&D research. In addition to our own discovery program, as part of our open innovation model we partner with companies to license drugs for patients in China and co-develop therapies to address leading causes of cancer death. We currently have a license and collaboration agreement with GSK for the development and commercialization of ZEJULA (niraparib) in mainland China, Hong Kong, and Macau. PRIME was a follow-on study to a previously conducted study called PRIMA, which demonstrated clinical benefit of niraparib in newly diagnosed patients with advanced ovarian cancer regardless of biomarker status. The PRIMA study enrolled a population at high risk of recurrence. Thirty-five percent of patients in PRIMA received an individualized starting dose (ISD) of niraparib based on their baseline weight and platelet count. To further evaluate the efficacy and safety of niraparib with an ISD in a broad population, we decided to conduct the PRIME study. We wanted to explore further whether we could decrease toxicity using an ISD and how it would affect clinical outcomes. The Phase 3 PRIME study was conducted at 29 hospitals in mainland China. PRIME was a randomized, placebo-controlled trial designed to evaluate the efficacy and safety of niraparib at an ISD as first-line maintenance therapy in a broad range of patients with newly diagnosed advanced ovarian cancer. All patients in PRIME received an ISD based on their baseline body weight and platelet count. (more…)
Author Interviews, Cancer Research, JAMA, NCI, Ovarian Cancer / 21.04.2023

MedicalResearch.com Interview with: Lauren Hurwitz, PhD Postdoctoral Fellow Division of Cancer Epidemiology & Genetics National Cancer Institute MedicalResearch.com: What is the background for this study? What are the main findings? Response: Prior studies have demonstrated that frequent (i.e., daily or near daily) use of aspirin is associated with a lower risk of developing ovarian cancer. We sought to determine if this risk reduction is also observed for individuals with greater genetic susceptibility to ovarian cancer, who may benefit more from preventive interventions. Our study found that individuals who took aspirin frequently had a lower risk of ovarian cancer, regardless of whether they had higher or lower genetic susceptibility to ovarian cancer. (more…)
Author Interviews, Breast Cancer, Cancer Research, Genetic Research, Ovarian Cancer / 22.07.2020

MedicalResearch.com Interview with: Prof Ranjit Manchanda MD, MRCOG, PhD Professor of Gynaecological Oncology & Consultant Gynaecological Oncologist NHS Innovation Accelerator (NIA) Fellow Integrated Academic Training Programme Director London Specialty School of Obstetrics & Gynaecology, Health Education England Specialty Research Lead for Gynaecological Cancer, NIHR, North Thames Clinical Research Network Cancer Research UK, Barts Centre | Queen Mary University of London Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine | Charterhouse Square | London Department of Gynaecological Oncology | Barts Health NHS Trust, Royal London Hospital MedicalResearch.com: What is the background for this study? Response: Around 10–20% of ovarian cancers and 6% breast cancers overall are caused by inheritable BRCA1/BRCA2 mutations. Women carrying BRCA1/BRCA2 mutations have a 17–44% risk of ovarian cancer and 69–72% risk of breast cancer until age 80 years. Most of these cancers can be prevented in unaffected BRCA1/BRCA2 women carriers. Women can opt for a range of options including screening, preventive, and reproductive choices to minimise their risk. The current approach uses established clinical-criteria/family-history (FH) based a priori BRCA probability thresholds to identify high-risk individuals eligible for BRCA testing. However, this requires individuals and health practitioners to recognise and act on a significant FH. BRCA carriers, who are unaware of their FH, unappreciative of its risk/significance, not proactive in seeking advice, or lack a strong FH (small families/paternal inheritance/chance) get excluded. Over 50% BRCA carriers do not fulfil clinical criteria and are missed. Despite >25 years of BRCA testing and effective mechanisms for prevention, current guidelines and access to testing pathways remain complex and associated with a massive under-utilisation of genetic testing. Only 20% of eligible women have accessed/undergone genetic testing and our earlier analysis showed that 97% of BRCA carriers in the population remain unidentified. Current detection rates are inadequate to identify all BRCA carriers and even doubling detection rates will not work. Why should we wait for decades for people to develop cancer before identifying BRCA carriers and unaffected at-risk family members to offer prevention?. This highlights substantial missed opportunities for early detection and prevention. A new population testing approach can change this. Jewish population studies show this is feasible, acceptable, has high satisfaction (91–95%), significantly reduces anxiety, doesn’t harm psychological well-being or quality of life, and is extremely cost-effective. However, this has not been evaluated in the general population and in particular across different  countries or health systems. The potential applicability and scope for this approach transcends continents and countries. Additionally, for interventions to be sustainable, they need to be cost-effective and affordable. We have undertaken a cost-effectiveness analysis of population based BRCA testing compared with current standard clinical testing of women designated as high risk, across high income countries (UK/USA/Netherlands), upper-middle income countries (China/Brazil), and low-middle income country (India). (more…)
ASCO, Author Interviews, OBGYNE, Ovarian Cancer / 12.06.2020

MedicalResearch.com Interview with: Robert L. Coleman, MD, FACOG, FACS Chief Scientific Officer US Oncology Research MedicalResearch.com: What is the background for this study? Response: For years, there has been general support for surgery in patients with recurrent ovarian cancer supported by reams of retrospective studies that suggest patients live longer if they have surgery preceding chemotherapy. Suggested hypotheses from these trials were that patients most likely to benefit from the procedure were those with good performance status (could tolerate the procedure), had long platinum-free interval (surrogate for potential for chemotherapy response) and those in whom all disease could be resected. Each of these are also characteristics that would portend a good prognostic cohort in general and would likely do better than other patients without these characteristics. So there was a strong selection bias in these retrospective surveys. Thus, the call for randomized trials. GOG-213 was launched in 2007 with 2 primary endpoints: 1. Determine the impact of adding bevacizumab to paclitaxel/carboplatin in patients with platinum-sensitive recurrent ovarian cancer, and 2. Determine if surgery increases overall survival. (more…)
ASCO, AstraZeneca, Author Interviews, Cancer Research, Ovarian Cancer / 02.06.2020

MedicalResearch.com Interview with: Mark Sims US Franchise Head Women’s Cancer & DNA Damage Response AstraZeneca  MedicalResearch.com: What is the background for this study? What are the main findings? Response: SOLO2 is a Phase III, randomized, double-blind, multicenter trial designed to determine the efficacy and safety of LYNPARZA tablets as a maintenance monotherapy compared with placebo, in patients with platinum-sensitive relapsed or recurrent gBRCA-mutated (BRCAm) ovarian cancer. The trial included 295 patients with germline BRCA1 or BRCA2 mutations who had received at least 2 prior lines of platinum-based chemotherapy and were in complete or partial response. The trial met its primary endpoint in October 2016, showing maintenance treatment with LYNPARZA significantly improved progression-free survival to a median of 19.1 months vs 5.5 months with placebo (a hazard ratio of 0.30; a 95% confidence interval of 0.22 to 0.41; a p value of <0.0001). (more…)
AACR, Author Interviews, Cancer Research, Ovarian Cancer / 23.12.2019

MedicalResearch.com Interview with: Rugang Zhang, Ph.D Professor & Co-Leader, Gene Expression & Regulation Program Deputy Director, The Wistar Institute Cancer Center MedicalResearch.com: What is the background for this study? Response: Although the majority of epithelial ovarian cancer (EOC) patients initially respond well to platinum therapy, relapse ultimately occurs, which remains a major challenge in the clinical management of EOC. Substantial evidence suggests that cancer stem-like cells (CSC) contribute to chemotherapy resistance and elimination of CSC prevents the therapeutic relapse including in EOCs. Thus, therapeutic elimination of EOC CSCs represents a promising approach to achieve a durable therapeutic outcome by preventing chemotherapy resistance. Platinum-based chemotherapies are known to induce senescence that limits the propagation of cells subjected to insults such as cancer chemotherapeutics. In contrast to apoptosis, senescent cells remain viable. Senescent cells secrete a plethora of pro-inflammatory cytokines and chemokines, which is termed senescence-associated secretory phenotype (SASP). Therapy-induced inflammation promotes tumor progression and therapy resistance, and the SASP is known to promote cancer stem-like cells. However, clinically applicable approaches to target stemness associated with therapy-induced senescence remain to be explored.  (more…)
Author Interviews, Breast Cancer, Cancer Research, Genetic Research, JAMA, Ovarian Cancer, USPSTF / 28.08.2019

MedicalResearch.com Interview with: Dr. Carol Mangione, M.D., M.S.P.H., F.A.C.P. Division Chief of General Internal Medicine and Health Services Research Professor of Medicine Barbara A. Levey, MD, and Gerald S. Levey, MD, endowed chair in Medicine David Geffen School of Medicine University of California, Los Angeles (UCLA) Professor of public health at the UCLA Fielding School of Public Health.  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Every year, too many American women are faced with the challenge of dealing with a cancer diagnosis related to potentially harmful mutations of the BRCA1 and BRCA2 genes.  However, the Task Force found that there are several steps women can take to determine if they’re potentially at increased risk for BRCA gene mutations – and if genetic counseling and BRCA testing are needed. It is important to note that while some women can benefit from risk assessment, counseling, and testing, these services are not for everyone. (more…)
Author Interviews, Biomarkers, Ovarian Cancer / 25.09.2018

MedicalResearch.com Interview with: Fabian Coscia PhD Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, German and Ernst Lengyel MD PhD Department of Obstetrics and Gynecology Section of Gynecologic Oncology University of Chicago, Chicago, IL  MedicalResearch.com: What is the background for this study? Response: Ovarian cancer is a very aggressive disease. Only one in six patients survives more than 10 years after the first diagnosis. This high mortality is primarily because the disease is usually detected late in its course, when the tumor has already spread from the ovaries to the surrounding organs in the abdomen. In an interdisciplinary collaboration between the Max Planck Institute of Biochemistry in Martinsried, Munich, the University of Chicago and the University of Copenhagen, we performed deep tissue proteomics on archived biobank material to identify drivers of long-term patient survival.  (more…)
Author Interviews, Breast Cancer, Cancer Research, Genetic Research, JAMA, Ovarian Cancer / 21.08.2018

MedicalResearch.com Interview with: Ambry GeneticsShuwei Li, PhD Principal Statistical Geneticist Ambry Genetics MedicalResearch.com: What is the background for this study? What are the main findings? Response: Breast cancer is the most commonly diagnosed cancer, while ovarian cancer is the fifth leading cause of death due to cancer, in US women. Since the discovery of BRCA1 and BRCA2, multiple genes have been reported as risk factors; however, it is still unclear whether the known findings represent the complete genetic landscape of breast and ovarian cancers. Our team performed exome sequencing on more than 10,000 breast and/or ovarian cancer patients and nearly 4,000 controls. We observed increased risk of breast cancer associated with PALB2, ATM, CHEK2 and MSH6 genes, and increased risk of ovarian cancer associated with MSH6, RAD51C, TP53 and ATM genes.   (more…)
Author Interviews, Brigham & Women's - Harvard, JAMA, Ovarian Cancer / 22.02.2018

MedicalResearch.com Interview with: Michael J. Barry, M.D., Task Force member Director of the Informed Medical Decisions Program Health Decision Sciences Center Massachusetts General Hospital. Professor of Medicine Harvard Medical School and Physician at Massachusetts General Hospital MedicalResearch.com: What is the background for this study? What are the main findings? Response: Ovarian cancer is the fifth leading cause of cancer death among women in the United States. It is hard to detect, and many women diagnosed with ovarian cancer do not show signs or symptoms early on. As a result, ovarian cancer is often diagnosed at a late stage, when it is hard to treat successfully. The U.S. Preventive Services Task Force looked at the latest evidence to see if screening women who do not have signs or symptoms of ovarian cancer can prevent them from dying of the disease. Unfortunately, we found that screening for ovarian cancer does not decrease the number of women who die, but it does lead to some women having unnecessary surgery to remove their ovaries. As a result, we are recommending against ovarian cancer screening in women who are not at high risk. (more…)
Author Interviews, Cancer Research, Ovarian Cancer / 22.01.2018

MedicalResearch.com Interview with: Dr. W.J. van Driel Gynaecologic Oncologist Antoni van Leeuwenhoek Amsterdam  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Our study reports on the results of a randomized phase 3 study in patients with FIGO stage III ovarian cancer who were ineligible for primary cytoreductive surgery and therefore treated with neo-adjuvant chemotherapy and interval cytoreductive surgery. Following optimal or complete cytoreductive surgery another 3 cycles of chemotherapy were given. During the interval cytoreductive surgery patients were randomized between surgery alone or surgery + HIPEC. During hyperthermic intraperitoneal administration of chemotherapy (HIPEC) the abdomen is perfused with cisplatin to expose any remaining minimal or microscopic disease to a high dose of heated chemotherapy. The main findings are that the addition of HIPEC to interval cytoreductive surgery resulted in longer recurrence-free survival and overall survival than surgery alone and the addition of HIPEC did not result in higher rates of side effects.  (more…)
Author Interviews, Chemotherapy, JAMA, Ovarian Cancer / 26.12.2017

MedicalResearch.com Interview with: Debra Richardson, MD, FACOG, FACS Associate Professor, Section of Gynecologic Oncology, Oklahoma TSET Phase I Program Stephensen Cancer Center The University of Oklahoma MedicalResearch.com: What is the background for this study? What are the main findings? Response: Ovarian cancer is the leading cause of gynecologic cancer deaths. Pazopanib is an oral multitarget tyrosine kinase inhibitor of VEGF receptors 1, 2, and 3; platelet-derived growth factor (PDGF) receptors α and β and c-KIT. Weekly paclitaxel is an active agent for recurrent ovarian cancer. This was a national, randomized, double-blind, placebo controlled phase 2b trial of weekly paclitaxel with or without pazopanib for the treatment of recurrent ovarian cancer. The primary objective was to estimate the progression-free survival (PFS) hazard ratio (HR) of the combination of weekly paclitaxel (80mg/m2 D1, 8, 15 every 28 days) and pazopanib (800mg PO daily) compared with weekly paclitaxel and placebo in women with persistent or recurrent ovarian cancer. 106 women were enrolled. There was no difference in median PFS, overall survival (OS), or proportion responding. Severe hypertension was more common on the pazopanib plus paclitaxel arm. More patients discontinued treatment on the paclitaxel arm for disease progression, and more on the pazopanib plus paclitaxel arm for adverse events. Patients with VEGFA CC genotype may be more resistant to weekly paclitaxel than those with the AC or AA genotype. (more…)
Author Interviews, Cancer, CDC, Ovarian Cancer, Race/Ethnic Diversity / 06.12.2017

MedicalResearch.com Interview with: Dr. Sherri Stewart, PhD Division of Cancer Prevention and Control CDC MedicalResearch.com: What do women most need to know about ovarian cancer detection and treatment? Response: There is no effective test to detect ovarian cancer at an early stage where treatment is most likely to be effective.  Many women mistakenly believe that the Pap test can detect ovarian cancer, but it does not. The Pap test is recommended only for the detection of cervical cancer.  Recognizing early symptoms of ovarian cancer and seeking timely care may help lead to detection of the cancer at an earlier stage, where treatment is likely to be more effective.  Symptoms – such  as abdominal and back pain, feeling full quickly after eating, and frequent urination – are often present among women with ovarian cancer.  Women should talk with their doctors if they experience any of these symptoms for 2 weeks or longer and the symptoms persist or worsen. If a woman is diagnosed with ovarian cancer, she should seek treatment from a gynecologic oncologist, a physician specially trained to treat ovarian cancer.  Ovarian cancer patients who have been treated by gynecologic oncologists have been shown to survive longer than those treated by other physicians.           (more…)
Author Interviews, ESMO, Immunotherapy, Ovarian Cancer / 14.10.2016

MedicalResearch.com Interview with: Dr. Mansoor Raza Mirza, MD Medical Director: Nordic Society of Gynecologic Oncology Board of Directors: Gynecologic Cancer Inter-Group (GCIG) Faculty: European Society of Medical Oncology (ESMO) Faculty: International Gynecologic Cancer Society (IGCS) Chief Oncologist, Rigshospitalet Copenhagen University Hospital Copenhagen, Denmark MedicalResearch.com: What is the background for this study? Response: Recurrent ovarian cancer is an area of significant unmet medical need, and there have been few therapeutic advances for these patients in the past few decades. Niraparib was studied to provide patients with recurrent ovarian cancer an option other than “watchful waiting,” potentially redefining the standard of care for the disease. The ENGOT-OV16/NOVA trial was a Phase 3 double-blind, randomized, placebo-controlled international study of maintenance treatment with niraparib compared with placebo. Niraparib successfully achieved the primary endpoint of prolonging progression-free survival versus placebo in all three prospectively defined primary efficacy populations: (more…)
Author Interviews, Nutrition, Ovarian Cancer, Race/Ethnic Diversity, Vitamin D / 19.09.2016

MedicalResearch.com Interview with: Bo (Bonnie) Qin, Ph.D. Post-Doctoral Associate Rutgers Cancer Institute of New Jersey New Brunswick, NJ 08903 MedicalResearch.com: What is the background for this study? Response: Ovarian cancer is the leading cause of death from gynecologic cancer in the US. African-American patients diagnosed with ovarian cancer tend to have a worse 5-year survival rate compared to their European-American patients. Therefore, identifying preventive factors in African-Americans women is particularly important. African Americans tend to consume less calcium and vitamin D from dietary sources, due to a higher prevalence of lactose intolerance, and supplemental intake. Meanwhile, darker color of the skin reduces the synthesis of vitamin D upon sun exposure. They together place African-American women at risk for calcium and vitamin D deficiency. It remains unknown whether calcium, vitamin D, lactose and dairy products are associated with ovarian cancer risk in African-American women and our study aimed to answer this question. (more…)
ASCO, Author Interviews, Journal Clinical Oncology, MD Anderson, Ovarian Cancer / 14.09.2016

MedicalResearch.com Interview with: Larissa A. Meyer, MD MPH F.A.C.O.G. Assistant Professor Dept of Gynecologic Oncology and Reproductive Medicine Houston, TX 77030-1362 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Despite the completion of two randomized controlled trials, controversy regarding the optimal approach for the treatment of advanced ovarian cancer remains. Our observational study highlights the importance of thoughtful selection of individuals for primary cytoreductive surgery for advanced ovarian cancer. Our results suggest that primary cytoreductive surgery may improve survival for patients with stage IIIC ovarian cancer who are likely to achieve an optimal cytoreduction, while neoadjuvant chemotherapy may be the preferred option for many women with stage IV ovarian cancer. (more…)
Author Interviews, Breast Cancer, Genetic Research, Mental Health Research, Ovarian Cancer, Psychological Science / 31.08.2016

MedicalResearch.com Interview with: Mag. Dr. Anne Oberguggenberger PhD Medizinische Universität Innsbruck Department für Psychiatrie, Psychotherapie und Psychosomatik Innsbruck Austria MedicalResearch.com: What is the background for this study? Response: Genetic counseling and testing is increasingly integrated in routine clinical care for breast- and ovarian cancer (BOC). Knowledge on follow-up psychosocial outcomes in all different groups of counselees is essential in order to improve follow-up care and counselees’ quality of life. (more…)
Author Interviews, Environmental Risks, NIH, OBGYNE, Ovarian Cancer / 18.08.2016

MedicalResearch.com Interview with: Clarice Weinberg, Ph.D. Deputy Branch Chief Biostatistics and Computational Biology Branch National Institute of Environmental Health Sciences National Institutes of Health Research Triangle Park, NC 27709 MedicalResearch.com: What is the background for this study? What are the main findings? Response: A number of studies have reported a link between genital use of talc powders and ovarian cancer. We wondered whether the practice of douching could contribute to that risk by moving fibers and chemicals into and up the reproductive tract. We are carrying out the Sister Study, a large cohort study that enrolled more than 50,000 women who each had a sister diagnosed with breast cancer and who are consequently at increased risk of ovarian cancer. During the Sister Study enrollment interview, we asked each of them about their douching and use of talc in the previous 12 months. During approximately 6 years of follow up, 154 participants developed ovarian cancer. Our statistical analyses did not show any relationship between talc use and risk of ovarian cancer, but we estimated that women who had said they douched had almost double the risk for ovarian cancer compared to women who did not douche. (more…)
Author Interviews, Beth Israel Deaconess, Biomarkers, Cost of Health Care, Medical Imaging, Ovarian Cancer / 22.07.2016

MedicalResearch.com Interview with: Katharine Mckinley Esselen, M.D. Instructor in Obstetrics, Gynecology and Reproductive Biology Beth Israel Deaconess Medical Center Brigham and Womens Hospital MedicalResearch.com: What is the background for this study? Response: There is no consensus on how to follow a patient in remission from ovarian cancer in order to detect recurrent disease. However, a 2009 randomized clinical trial demonstrated that using CA-125 blood tests for routine surveillance in ovarian cancer increases the use of chemotherapy and decreases patient’s quality of life without improving survival compared with clinical observation. Published guidelines categorize CA-125 tests as optional and discourage the use of radiographic imaging for routine surveillance. Thus, this study aims to examine the use of CA-125 tests and CT scans at 6 Cancer Centers and to estimate the economic impact of this surveillance testing for ovarian cancer. (more…)
Author Interviews, Ovarian Cancer / 01.07.2016

MedicalResearch.com Interview with: Professor Richard Morgan Director, The Institute of Cancer Therapeutics University of Bradford Richmond Road Bradford UK MedicalResearch.com: What is the background for this study? What are the main findings? Response: Ovarian cancer is the 5th most common cause of cancer-related death in woman and the most deadly gynaecological cancer. One of the reasons for this is its resistance to conventional chemotherapy. Although tumours often respond well at first, showing dramatic shrinkage in the first few months of treatment, they usually grow again and at this point they are no longer sensitive to the drugs. We studied the role of HOX genes in ovarian cancer. The HOX genes play an important role in the early development of the embryo but are usually switched off in adult cells. However, many cancers, including ovarian cancer, turn them back on. Previous work suggested that they might have an important role in promoting the rapid proliferation of cancer cells. (more…)
Author Interviews, Breast Cancer, Genetic Research, Ovarian Cancer / 26.05.2016

MedicalResearch.com Interview with: Sibaji Sarkar Ph.D Instructor of medicine Boston University School of Medicine Boston MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Sarkar: Although breast and ovarian cancers have different clinical presentations, there are certain molecular events that are conserved between the two types of cancers. For example, mutation in a few genes, such as BRCA1, BRCA2, is an indicator of possible development of both breast and ovarian cancers. ARHI, a pro-apoptotic imprinted gene is epigenetically silenced in both breast and ovarian cancers. A similar pattern was observed in microRNA as well. There are also several genes which are differentially expressed in these two types of cancers but few of these striking resemblances led us to investigate whether they have a common origin. In this paper, we compared genetic and epigenetic events in both breast and ovarian cancers and we hypothesize that they may have similar origin (mechanism of formation of cancer progenitor cells), which should be regulated by epigenetic mechanism. (more…)
AACR, Author Interviews, Ovarian Cancer, Technology / 29.02.2016

MedicalResearch.com Interview with: Janet A. Sawicki, Ph.D. Deputy Director and Professor Lankenau Institute for Medical Research 100 Lancaster Ave. Wynnewood, PA 19096 MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Sawicki: This study addresses the need for a more effective therapy for ovarian cancer. HuR is an RNA-binding protein that is present in high amounts in ovarian tumor cells compared to amounts in normal cells. HuR regulates the expression of thousands of genes that promote the survival of tumor cells. Thus, it is an ideal therapeutic target to suppress ovarian tumor growth. In this study, we used a small interfering RNA (siRNA) to investigate the impact of suppressing HuR expression on ovarian tumor growth in an ovarian cancer mouse model. We made use of the ability to conjugate a novel DNA dendrimer nanocarrier, 3DNA®, to both siHuR and a tumor-targeting moiety to suppress HuR expression specifically in tumor cells following systemic administration while avoiding toxicity in healthy cells. Systemic administration of siHuR-conjugated FA-3DNA to ovarian tumor-bearing mice suppressed tumor growth and ascites development, and significantly prolonged lifespan. Gene expression analysis identified multiple HuR-regulated genes in tumor cells as evidenced by changes in their expression upon HuR inhibition. These HuR-regulated genes function in multiple essential cellular molecular pathways, a finding that sets this therapeutic approach apart from other therapies that target a single gene. (more…)
Author Interviews, OBGYNE, Ovarian Cancer, Radiology / 22.01.2016

More on Ovarian Cancer on MedicalResearch.com MedicalResearch.com Interview with: Dirk Timmerman, MD PhD Department of Development and Regeneration Department of Obstetrics and Gynecology University Hospitals Leuven Leuven, Belgium Medical Research: What is the background for this study? What are the main findings? Dr. Timmerman: Ovarian cancer is the most aggressive and lethal gynecological malignant neoplasm. The prognosis of ovarian cancer is poor, with only about 40% of patients still alive five years after being diagnosed. The preoperative characterization of an adnexal tumor is fundamental for selecting the optimal management strategy. An accurate differentiation between benign and malignant masses can lead to optimal referral of patients with malignant diseases to gynecological oncology centers for further diagnostics and treatment, which positively influences the prognosis. On the other hand, it may help in safely selecting patients with benign ovarian masses for minimally invasive or fertility sparing surgery, and in some cases maybe even conservative follow-up. The International Ovarian Tumor Analysis (IOTA) study is the largest diagnostic accuracy study of its kind. Transvaginal ultrasound is a cheap and very accessible imaging technique. Using ultrasound features, which are easy to assess by a trained examiner, we proposed a model to define the individual risk of malignancy for each patient presenting with an adnexal tumor. This could considerably impact on the morbidity and mortality associated with adnexal pathology. (more…)
ASCO, Author Interviews, Immunotherapy, Ovarian Cancer / 02.12.2015

MedicalResearch.com Interview with: Junzo Hamanishi  M.D., Ph.D. Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine Assistant Professor Kyoto Japan Medical Research: What is the background for this study? Dr. Hamanishi: More than 70% of patients with advanced ovarian cancer who achieve remission ultimately relapse and there are few effective treatments for these patients. Because the development of new treatment strategies for these patients is urgently required, we have focused on and studied the potential of cancer cells to escape from host immunity with PD-1/PD-L1 immunosuppressive signal in the tumor microenvironment to find new treatment strategies to overcome this phenomenon, collaborating with Professor Honjo who discovered PD-1 since 2006. Therefore, we conducted a phase II clinical trial in 20 platinum-resistant, recurrent ovarian cancer patients to evaluate the safety and anti-tumor efficacy of anti-PD-1 antibody (nivolumab) with 2 cohort at a dose of 1 or 3 mg/kg (constituting two 10-patient cohorts). Medical Research: What are the main findings? Dr. Hamanishi: This study is the first investigator-initiated phase II clinical trial testing the safety and efficacy of nivolumab against platinum-resistant ovarian cancer. In the 20 patients in whom responses could be evaluated, the best overall response was 15%, including two patients with a durable complete response (3mg/kg cohort). The disease control rate in all 20 patients was 45%. The median progression-free survival was 3.5 months, with a median overall survival of 20.0 months. Especially in the 3 mg/kg cohort, two patients achieved a complete response, and disease stabilized in another two patients. The objective response rate in 3mg/kg cohort cohort was 20% and disease was controlled in 40% of the higher-dose group. In the four patients who demonstrated an antitumor response, responses were durable and evident. Grade 3 or 4 treatment-related adverse events (AE) occurred in eight out of 20 patients or 40% overall. However, the frequency of AEs were not different in 2 cohorts. (more…)
Author Interviews, Ovarian Cancer, Technology / 18.11.2015

MedicalResearch.com Interview with: Professor John McDonald PhD Director of its Integrated Cancer Research Center School of Biology at the Georgia Institute of Technology Medical Research: What is the background for this study? What are the main findings? Response: Ovarian cancer is a deadly disease because it cannot be diagnosed at early stages when it can be most effectively effectively treated. It has long been recognized that there is a great need for an accurate diagnostic test for early stage ovarian cancer. Until now, efforts to develop a highly accurate way to detect early stage ovarian cancer have been unsuccessful. We have used a novel approach that integrates advanced methods in analytical chemistry with advanced machine learning algorithms to identify 16 metabolites that collectively can detect ovarian cancer with extremely high accuracy (100% in the samples tested in our study) (more…)
AACR, Author Interviews, NIH, Nutrition, Ovarian Cancer, Race/Ethnic Diversity / 13.11.2015

MedicalResearch.com Interview with: Bo (Bonnie) Qin, PhD Postdoctoral associate at Rutgers Cancer Institute of New Jersey Medical Research: What is the background for this study? What are the main findings? Response:  Ovarian cancer is among the top five causes of cancer death among women in the US. Compared to white women, African-American women tend to have a worse 5-year survival rate of ovarian cancer. It highlights a critical need for identifying preventive factors in African Americans, particularly through dietary modification, which is relatively low cost and low risk compared to medical treatments. We found that adherence to an overall healthy dietary pattern i.e. Alternate Healthy Eating Index (AHEI)-2010 may reduce ovarian cancer risk in African-American women, and particularly among postmenopausal women. Adherence to the current Dietary Guidelines for Americans i.e. Healthy Eating Index-2010, were also strongly associated with reduced risk of ovarian cancer among postmenopausal African-American women. (more…)
Author Interviews, Ovarian Cancer / 18.08.2015

Oleh Taratula,PhD Assistant Professor Oregon State University/Oregon Health & Science University College of PharmacyMedicalResearch.com Interview with: Oleh Taratula, PhD Assistant Professor Oregon State University/Oregon Health & Science University College of Pharmacy MedicalResearch: What is the background for this study? Dr. Taratula: The background for the study consists of previous work we had published in the lab using photodynamic therapy (PDT) as the stand alone treatment modality. We were successful in synthesizing and incorporating the photodynamic nanoplatform in the treatment for ovarian cancer, but our current graduate student, Canan Schumann said he could make the therapy more efficient using his current research on gene therapy. The gene therapy he is currently working on is the delivery of siRNA targeted to the multifaceted oncogenic protein DJ-1 which has been implicated in antioxidative stress defense as well as the overall survival of ovarian cancer. Cancer is highly intelligent able to adapt quickly to new insults that it comes across, even ROS formed inside the cell. Cancer cells can even upregulate a whole host of antioxidant stress response proteins to combat the formation of or scavenge already created ROS. The idea was can we combine our currently used PDT, which uses the generation of reactive oxygen species (ROS) as its cytotoxic mechanism of action, coupled with gene therapy targeted to DJ-1, in hope to drastically increase ROS inside the cell leading to a more pronounced cell death. (more…)
Author Interviews, Breast Cancer, Genetic Research, JAMA, Ovarian Cancer / 13.08.2015

Leif W. Ellisen, M.D., Ph.D Professor of Medicine, Harvard Medical School Program Director, Breast Medical Oncology Co-Leader, Breast Cancer Program MGH Research Scholar MGH Cancer Center Boston, MA 02114MedicalResearch.com Interview with: Leif W. Ellisen, M.D., Ph.D Professor of Medicine, Harvard Medical School Program Director, Breast Medical Oncology Co-Leader, Breast Cancer Program MGH Research Scholar MGH Cancer Center Boston, MA 02114 Medical Research: What is the background for this study? What are the main findings? Dr. Ellisen: The traditional approach to genetic testing for women with suspected hereditary breast and/or ovarian cancer risk is to test for BRCA1 and BRCA2 alone. Recent studies have shown that testing with a multi-gene panel finds relevant risk gene mutations in substantially more women than does testing for BRCA1 and BRCA2 alone. However, one of the concerns about broader multi-gene testing has been that the results really wouldn’t change what you told women about their risk and management – either because the risk associated with the other genes may not be as high as for BRCA1/2, or because the clinical practice guidelines associated with some of the other genes are less specific. Our study sought to determine how often testing such women using a multi-gene panel would find mutations in genes other than BRCA1/2, and more importantly to ask whether finding those mutations would change how you would manage the patient and their family. We found that multi-gene panel testing finds relevant risk gene mutations in substantially more women (approximately 40% more) than does testing for BRCA1 and BRCA2 alone. Furthermore, in a case-by-case analysis we showed that finding mutations in these other genes is likely to change the clinical management that is considered or recommended for the majority of the mutation-positive women and their families.  Notably, our analysis of the predicted management change is based not just on the gene mutation alone, but on how the gene appears to be behaving in that particular family. (more…)