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…)
Author Interviews, Cancer Research, Chemotherapy, JNCI, MD Anderson, Ovarian Cancer / 26.05.2015

Wei Zhang, Ph.D., Professor Department of Pathology Director, Cancer Genomics Core Lab University of Texas MD Anderson Cancer Center Houston, Texas 77030MedicalResearch.com Interview with: Wei Zhang, Ph.D., Professor Department of Pathology Director, Cancer Genomics Core Lab University of Texas MD Anderson Cancer Center Houston, Texas 77030 Medical Research: What is the background for this study? What are the main findings? Dr. Zhang: Epithelial ovarian cancer remains the most lethal gynecological malignancy. The 5-year survival rate for patients with advanced ovarian cancer is only 30-40%, and acquired resistance to platinum is considered a major factor in disease relapse. A major challenge in cancer treatment is the resilient ability of cancer cells to repair DNA damage caused by chemotherapy agents.  In this study, we found that adding a molecule called miR-506 to standard chemotherapy can help cells overcome drug resistance, so that the chemotherapy drugs remain effective against ovarian cancer. This research supports a new combination approach, which may substantially benefit patients with this deadly disease. (more…)
Author Interviews, Lancet, Ovarian Cancer, Surgical Research / 22.05.2015

MedicalResearch.com Interview with: Mr Matthew Nankivell MRC Clinical Trials Unit at University College London Institute of Clinical Trials and Methodology Aviation House, London UK Medical Research: What is the background for this study? What are the main findings? Response: Ovarian cancer is diagnosed in over 7000 women each year in the UK. Over 75% of these already have advanced disease, for which the standard treatment is surgery followed by platinum based chemotherapy. The prognosis for these patients remains poor however, with less than 25% surviving for 5 years. There is consistent evidence that achieving optimal debulking (meaning less than 1cm of residual tumour after surgery) is key to increasing survival. The theory tested in Chorus is that giving the chemotherapy before surgery (neo-adjuvantly) would be as least as effective as giving it post-operatively, and may in fact increase the chance of achieving optimal debulking, and subsequently living for longer. In Chorus we randomised 552 women to receiving either the current standard of immediate surgery followed by chemotherapy, or chemotherapy followed by surgery. The trial met its primary aim of showing that neo-adjuvant chemotherapy was no worse than post-operative chemotherapy, with median survival times of 24.1 and 22.6 months respectively. The proportion of women achieving optimal debulking increased from 41% in the post-operative chemotherapy group to 73% in the neo-adjuvant chemotherapy group. Additionally we saw that fewer women experienced serious post-operative complications having had neo-adjuvant chemotherapy (14% vs 24%), and fewer women died within 28 days of surgery (<1% vs 6%). There is a planned meta-analysis, to combine the data from Chorus with those from a similar European trial, which will allow further investigations to take place, and may allow the identification of groups of women who are more likely to benefit from one or other of the approaches. (more…)
AACR, Author Interviews, Breast Cancer, NIH, Ovarian Cancer / 03.05.2015

Dr. Victoria L. Chiou, MD Medical Oncology Fellow Women’s Malignancies Branch National Cancer InstituteMedicalResearch.com interview with Dr. Victoria L. Chiou, MD Medical Oncology Fellow Women’s Malignancies Branch National Cancer Institute MedicalResearch: What is the background for this study? What are the main findings? Dr. Chiou: We studied the effects of different treatments in ovarian and breast cancer cell lines with and without BRCA1 mutation in the laboratory. Our discovery that olaparib pretreatment before carboplatin led to decreased carboplatin-induced DNA damage in tumor cells carrying BRCA1 mutation led us to a novel clinical question. We wanted to further understand whether there was an optimal way to deliver a combination of the new tablet formulation of olaparib with carboplatin chemotherapy in women with gynecologic and breast cancers. We launched our clinical trial to test this important question. Overall, we are pleased that the drug combination of olaparib and carboplatin chemotherapy can be given safely together, with preliminary activity in women with breast and ovarian cancer associated with germline BRCA mutations. We are excited to report the findings of this study, which is the first to report preclinical and clinical data on sequence specificity for this drug combination in this patient population. (more…)
Author Interviews, Nature, Ovarian Cancer / 29.01.2015

Dr. Terry Magnuson PhD Vice Dean for Research Department of Genetics, School of Medicine University of North Carolina at Chapel Hill Chapel Hill, North Carolina 27599MedicalResearch.com Interview with: Dr. Terry Magnuson PhD Vice Dean for Research Department of Genetics, School of Medicine University of North Carolina at Chapel Hill Chapel Hill, North Carolina 27599 Medical Research: What is the background for this study? What are the main findings? Response: Ovarian clear-cell carcinoma is a lethal form of ovarian cancer with limited therapeutic options. Recent patient-derived tumor sequencing studies support a strong genetic basis for the disease, but the roles of gene mutations in cancer causation are still unclear. We observed rapid induction of ovarian clear-cell carcinoma in mice that were genetically engineered to carry mutations in ARID1A and PIK3CA−the two most frequently mutated genes. Comparisons between human and mouse tumors uncovered a downstream role for the Interleukin-6 (IL-6) cytokine-signaling pathway in tumor progression. Thus, ARID1A and PIK3CA mutations cause ovarian clear-cell carcinoma and promote tumor cell growth by acting upon the IL-6 signaling pathway. (more…)
Author Interviews, Biomarkers, BMJ, Ovarian Cancer / 03.11.2014

Ben Van Calster PhD Department of Development and Regeneration KU Leuven, Herestraat Leuven, BelgiumMedicalResearch.com Interview with: Ben Van Calster PhD Department of Development and Regeneration KU Leuven, Herestraat Leuven, Belgium   MedicalResearch: What is the background for this study? What are the main findings? Dr. Van Calster: Ovarian cancer is a very common type of cancer among women, with over 200,000 new cases per year worldwide. It is the most lethal of gynecological malignancies. Research has shown that the referral of patients with ovarian cancer to specialized gynecological oncologists in high volume centers improves survival. However, audits in Europe and the United States also show that only a minority of women with ovarian cancer are appropriately triaged to receive specialist care. In addition, different types of malignancies are not treated in the same way. Hence optimal personalized management of an ovarian tumor hinges on the detailed preoperative diagnosis of its nature. Unfortunately, current prediction models focused on the discrimination between benign and malignant tumors without further specification of the likely type of malignancy. Various prediction models and rules have been developed to help predict whether an ovarian mass is benign or malignant. A recent systematic review meta-analysis has shown that the IOTA model LR2 and simple rules perform better than any other previous test. However none of these tests give anything other than a dichotomous outcome – i.e. cancer or non-cancer. In practice the position is more nuanced. The ADNEX model estimates the likelihood that a tumor is benign, borderline malignant, stage I cancer, stage II-IV cancer, or secondary metastatic cancer. This model is the first that is able to differentiate between benign and these four subtypes of malignancy. To do so, ADNEX uses three clinical predictors (age, serum CA-125 level, and type of center), and six ultrasound characteristics of the tumor (maximum diameter of lesion, proportion of solid tissue, more than 10 cyst locules, number of papillary projections, acoustic shadows, and ascites). The model is based on data from almost 6,000 women recruited at 24 centers in 10 countries. (more…)
Ovarian Cancer / 06.06.2014

Sean C. Dowdy, MD, FACS Professor and Chair, Division of Gynecologic Surgery Vice-Chair for Research, Department of Obstetrics and Gynecology Co-Leader, Women’s Cancer Program Mayo Clinic College of Medicine MedicalResearch.com Interview with: Sean C. Dowdy, MD, FACS Professor and Chair, Division of Gynecologic Surgery Vice-Chair for Research, Department of Obstetrics and Gynecology Co-Leader, Women’s Cancer Program Mayo Clinic College of Medicine MedicalResearch.com: What are the main findings of the study? Dr. Dowdy: This study was a collaboration between four groups in 3 countries to determine if a genetic “signature” could predict which patients with ovarian cancer benefit from Bevacizumab (a very expensive drug with marginal benefit in patients with ovarian cancer). We hypothesized that while benefit may be marginal in a large group, patients with specific genetic changes could derive significant benefit from it. Using gene expression arrays (analyzing over 18,000 genes) we separated patients into four subgroups as described by The Cancer Genome Atlas (TCGA). We show that patients in the proliferative and mesenchymal groups had a 8-10 month improvement in outcome compared to a 3 month improvement for the other two groups (immunoreactive and differentiated). (more…)
OBGYNE, Ovarian Cancer / 15.04.2014

Barbara A. Cohn, Ph.D. Director, Child Health and Development Studies A Project of the Public Health Institute Berkeley, CA 94709MedicalResearch.com Interview with: Barbara A. Cohn, Ph.D. Director, Child Health and Development Studies A Project of the Public Health Institute Berkeley, CA 94709   MedicalResearch.com: What are the main findings of the study?
  • Women with irregular menses had a statistically significant 2.4 fold increase in risk of death due to any form ovarian cancer, and a statistically significant 3-fold increase in risk of death due to late stage serous disease. Consistent with these findings, the incidence of late stage disease at diagnosis, and late stage serous cancer was increased about 2-fold in women with irregular menses.
  • Irregular menses was defined as irregular cycles (variation of 10 days or more) or infrequent cycles (>35 days) or history of annovulatory cycles identified during an in-person interview with women at an average age of 26 years or mentioned in their medical records. (more…)
Cancer Research, Heart Disease, MD Anderson, Ovarian Cancer / 08.10.2013

Anil K. Sood MD Department of Gynecologic Oncology The University of Texas MD Anderson Cancer Center Unit 1362, PO Box 301439, Houston, TX, 77030MedicalResearch.com Interview with: Anil K. Sood MD Department of Gynecologic Oncology The University of Texas MD Anderson Cancer Center Unit 1362, PO Box 301439, Houston, TX, 77030 MedicalResearch.com: What are the main findings of the study? Dr. Sood: For women with newly diagnosed ovarian cancer, high heart rate at diagnosis (tachycardia), venous thromboembolism (VTE) occurring after diagnosis and pulmonary hypertension post-diagnosis are independently related to reduced survival after controlling for tumor stage, grade, and extent of cytoreduction.  Women with tachycardia lived an average of 4.0 years after diagnosis compared with 5.9 years for women without tachycardia, a 32% reduction in duration of survival.  Patients who experienced VTE lived a median 4.1 years after diagnosis, compared with 6.4 yrs for patients who did not experience VTE. (more…)