Author Interviews, Ovarian Cancer / 04.11.2024

MedicalResearch.com Interview with: Alessia Baccarini, PhD Assistant Professor Dept. of Immunology and Immunotherapy (DII) Icahn School of Medicine at Mount Sinai New York, New York 10029 MedicalResearch.com: What is the background for this study? Response: Ovarian cancer is characterized by a complex tumor microenvironment (TME) that significantly contributes to resistance against immunotherapy, particularly immune checkpoint blockade (ICB) therapies like anti-PD-1. Understanding the extracellular signals—such as cytokines and chemokines—that ovarian cancer cells utilize to create an immunosuppressive TME is critical for improving treatment outcomes. Our research focuses on elucidating how these signaling factors contribute to tumor growth and immune evasion. We utilized a novel genomic functional approach called Perturb-map to study intratumoral heterogeneity (ITH) in ovarian cancer within a mouse model, allowing us to investigate the communication between ovarian cancer cells and immune cells.  (more…)
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…)