Author Interviews, Biomarkers, Cancer Research / 28.11.2018

MedicalResearch.com Interview with: Ricardo Alvarez MD MSc Medical Director of the Breast Cancer Center Director of Cancer Research Cancer Treatment Centers of America, CTCA Atlanta MedicalResearch.com: What is the background for this study? What are the main findings? Response: “The background of this study comes from five years of experience in one of our precision medicine programs that was launched in 2013 and this is the experience of a group of personnel from a hospital that helps physicians in five different hospitals that are a part of the CTCA network and for physicians who order a next generation sequencing test. In this particular report, we have only one vendor, and that is Foundation Medicine and we analyze three different genomic platforms, Foundation One test, Foundation Act and Foundation One Hem. In total, approximately 8,800 tests have been analyzed and that was the presentation at ESMO 2018. It’s important that the Precision Medicine Program (PMed) helps physicians to identify actionable and potentially actionable targets for the result of this test so patients can be treated with targeted therapy, and this can be done by selecting clinical trials or recommending patients to be treated off-label agents. When we say off label, meaning that they are not specifically FDA-approved drugs for this indication that we are treating.” (more…)
Author Interviews, Cancer Research, Cost of Health Care, JAMA, Pharmacology / 26.11.2018

MedicalResearch.com Interview with: Abiy Agiro, PHD HealthCore Inc Wilmington, Delaware  MedicalResearch.com: What is the background for this study? Response: Biosimilar approval pathway, authorized in 2010 by the Biologics Price Competition and Innovation Act as part of the Affordable Care Act, aims to increase adoption of biosimilar products and generate significant cost savings to payers and patients alike. Biosimilar filgrastim, used to prevent febrile neutropenia, is one of the first biosimilars to be approved in the United States. A large scale, post-approval real-world analysis was needed that compares biosimilar filgrastim to the original drug for safety and efficacy. (more…)
Author Interviews, Cancer Research, JAMA / 26.11.2018

MedicalResearch.com Interview with: Ola Landgren, MD, PhD Professor of Medicine Chief, Myeloma Service Department of Medicine Memorial Sloan Kettering Cancer Center New York, NY 10065 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Meta-analysis show that minimal residual disease (MRD) negativity is a strong predictor of longer progression-free survival (PFS). Emerging data show that an increasing proportion of newly diagnosed multiple myeloma patients obtain MRD negativity after modern combination therapy, even in the absence of bone marrow transplant. The first generation of 3-drug combination therapy (RVd) was associated with quite high rates of peripheral neuropathy which may be life-long. The current study was designed to define the rates of peripheral neuropathy in newly diagnosed multiple myeloma treated with the second generation of 3-drug combination therapy (KRd), and per default delayed transplant (i.e. collection of stem cells which were stored for potential future use). This single arm, phase 2 study found no cases of grade 3 peripheral neuropathy. The rates of MRD negativity wereunprecedented; 28 of 45 patients achieved MRD-negative CR (62%). The durability of MRD-negative CR has been observed up to 70 months (median duration 52.4 months). Patients who achieved MRD negativity by the end of cycle 8 had a 78% reduced risk of progression. The results were regardless of age or cytogenetic risk category. The results from this second generation of 3-drug combination therapy (KRd) without transplant,  compare favorably to first generation of 3-drug combination therapy (RVd) followed by stem cell transplant. (more…)
Author Interviews, Breast Cancer, Cancer Research, JNCI / 09.11.2018

MedicalResearch.com Interview with: Angela Mariotto PhD Chief of the Data Analytics Branch Surveillance Research Program (SRP) Division of Cancer Control and Population Sciences National Cancer Institute (NCI MedicalResearch.com: What is the background for this study? Response: Progressing to metastatic breast cancer (MBC) is one of the major concerns for women diagnosed with early-stage breast cancer. Before our study there were no reliable numbers on risk of metastatic breast cancer recurrence after a (non-metastatic) breast cancer diagnosis, as registries do not routinely collect this data. (more…)
Author Interviews, Cancer Research, Exercise - Fitness / 10.10.2018

MedicalResearch.com Interview with: Laurien Buffart, PhD Chair Amsterdam eXercise in Oncology (AXiON) research Departments of Epidemiology & Biostatistics and Medical Oncology VUmc  Amsterdam | The Netherlands MedicalResearch.com: What is the background for this study? What are the main findings?  Response: There is evidence from randomized controlled trials that exercise has beneficial effects on physical fitness, fatigue, quality of life and self-reported physical function during and following cancer treatment. The magnitude of the effects, however, often appear modest, possibly because interventions rarely target patients with worse symptoms and quality of life. Based on individual patient data from 34 randomized controlled trials, we found that exercise interventions during cancer treatment are effective in maintaining muscle strength and quality of life, regardless of their baseline values. Offering exercise interventions post cancer treatment to patients with a relatively high muscle strength and quality of life does not appear to further improve these outcomes. For aerobic fitness, exercise interventions during treatment had larger effects in patients with higher baseline aerobic fitness, whereas all patients were able to improve aerobic fitness post treatment. Greater effects on fatigue and self-reported physical function were found for patients with worse baseline fatigue and physical function, both during and post-treatment.  (more…)
AACR, Author Interviews, Cancer Research, MD Anderson, University Texas / 01.10.2018

MedicalResearch.com Interview with: Filip Janku, MD, PhD Associate Professor, Investigational Cancer Therapeutics (Phase I Clinical Trials Program) Center Medical Director, Clinical and Translational Research Center The University of Texas MD Anderson Cancer Center Houston, TX 77030 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Clostridium novyi-NT is an attenuated strain of bacteria Clostridium, which induced a microscopically precise, tumor-localized response in a rat brain tumor model and in companion dogs bearing spontaneous cancers. Clostridium novyi-NT can only grow in hypoxic (low-oxygen) tumor environment and destroys cancer cells by secreting lipases, proteases, and other hydrolytic enzymes; recruiting inflammatory cells to tumors eliciting anti-tumor immune responses in animals. Furthermore, intratumoral injection can plausibly induce an immune mediated abscopal effect in non-injected tumor sites. Therefore, we designed a phase I dose-finding study to test for safety and tolerability of the single intratumoral injection of Clostridium novyi-NT in 24 patients with advanced cancers with no available standard therapies. We also designed experiments to study activation of antitumor immune response in blood and tumor samples from patients undergoing the therapy. We demonstrated that single dose of intratumoral injection of Clostridium novyi-NT is feasible and has led to significant destruction of injected tumor masses. Adverse events, which were often related to the tumor destruction at the infected site, could have been significant but mostly manageable. Correlative studies of pre-treatment and post-treatment tumor and blood samples suggested immune response to therapy. (more…)
Author Interviews, Cancer Research, HPV, UCLA / 28.09.2018

MedicalResearch.com Interview with: Manon Eckhardt, PhD Gladstone Institutes The Quantitative Biosciences Institute University of California San Francisco  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Infection with Human Papillomavirus (HPV) causes 5% of all cancers worldwide, including cervical cancer and an increasing number of head and neck cancers. Most cancers are caused by mutations in genes, leading to the production of malfunctioning proteins that result in unconstrained cell division. However, certain viruses like HPV can cause cancer without introducing mutations. In this study, we compared cancers of the same type (i.e. head and neck) that are caused by either mutation or virus infection to identify important processes that are dysregulated in both subsets. We hypothesized that identifying which proteins the virus binds can lead the way to prioritize which of the proteins and cellular processes (pathways) that are affected in cancer cells are most important. To do this, we identified the complete set of human proteins that interact with HPV. We next determined genes that were more frequently mutated in non-viral cancers, and combined both data sets. The proteins we find to be both binding to HPV and mutated in non-viral cancers will be potential targets for new, more specific drug development, and help better understand the development of head and neck cancer. From the many pathways we identified in this study, we highlighted two pathways with further mechanistic studies: the oxidative stress response, which helps cancer cells survive, as well as a pathway that allows the cancer to spread to other parts of the body. (more…)
Author Interviews, Cancer Research, Gastrointestinal Disease, Microbiome, Science / 27.09.2018

MedicalResearch.com Interview with: Joao Xavier PhD Associate Faculty Member | Computational & Systems Biology Memorial Sloan Kettering Cancer Center New York, NY 10065  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Our team at Memorial Sloan Kettering has been investigating the intestinal microbiota of patients receiving bone marrow transplantations for more than eight years now. We have found through several studies that these patients lose important healthy bacteria from their microbiota, and that these losses are mostly caused by the antibiotics given as prophylaxis or to treat infections. We also found that the drastic changes in the microbiota composition, especially the intestinal dominations by bacteria such as Enterococcus, increase the risk of transplant-related complications and lowered patient survival. We aimed to determine the feasibility of autologous microbiota transplant (auto-FMT) as a way to reconstitute lost bacteria. This randomized study found that indeed auto-FMT could reconstitute important microbial groups to patients.  (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, Cancer Research, Genetic Research, JAMA, Yale / 22.09.2018

MedicalResearch.com Interview with: Michael F. Murray, MD, FACMG, FACP Director for Clinical Operations in the Center for Genomic Health Yale School of Medicine MedicalResearch.com: What is the background for this study? Response: Population screening for the cancer risk associated with the BRCA1 and BRCA2 genes has been suggested by some.  We screened a cohort of about 50,000 adult patient volunteers at Geisinger Health System in Pennsylvania for this risk.  (more…)
Author Interviews, Breast Cancer, Cancer Research, Chemotherapy, Radiation Therapy / 22.08.2018

MedicalResearch.com Interview with: Kathleen Horst, MD Associate Professor of Radiation Oncology (Radiation Therapy) Stanford University Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: We were interested in focusing on young women with breast cancer as this is a high-risk patient population that is not studied on its own in clinical trials. Furthermore, the available data on treating breast cancer with neoadjuvant chemotherapy (NAC) does not include detailed outcomes for women under the age of 40 years. Because most women who are diagnosed with breast cancer in this age group will have aggressive disease, most of them will be treated with NAC followed by surgery. From prospective randomized trials we know that women with breast cancer who attain a pathologic complete response (PCR) to neoadjuvant chemotherapy fare significantly better than those who do not. In addition, existing data suggest that a complete response in the lymph nodes also portends a better prognosis. This is the foundation for the currently ongoing NSABP B-51/RTOG 1304 trial, which is evaluating the role of nodal irradiation in those women who attain a pathologic complete response in the lymph nodes after NAC. We wanted to know whether differences in pathologic response in the breast versus lymph nodes led to different clinical outcomes in this patient group. We evaluated outcomes following neoadjuvant chemotherapy for breast cancer in 155 women age 40 and younger. We focused on pathologic response in the breast and lymph nodes as predictors of disease recurrence and survival. We found that any residual disease in either the breast or lymph nodes lessened the chance of cure significantly. Importantly, women who attained a complete response in the lymph nodes but continued to have residual disease in the breast fared just as poorly as those who remained lymph node positive following neoadjuvant chemotherapy.  (more…)
Author Interviews, Cancer Research, JAMA, Prostate Cancer / 26.07.2018

MedicalResearch.com Interview with: Alison L. Allan, PhD Department of Oncology, Western University London Regional Cancer Program, London Health Sciences Centre London, Ontario, Canada  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: This was an international collaborative study between Lawson Health Research Institute (London, ON), Memorial Sloan Kettering Cancer Center (New York), the Royal Marsden (London, UK) and molecular diagnostics company Epic Sciences (San Diego, CA). The study used a liquid biopsy test developed by Epic Sciences that examines circulating tumour cells (CTCs) in blood samples from patients with advanced prostate cancer who are deciding whether to switch from hormone-targeting therapy to chemotherapy. CTCs are cancer cells that leave a tumour, enter the blood stream and invade other parts of the body, causing the spread of cancer. The test identifies whether or not a patient’s CTCs contain a protein in the nucleus called AR-V7. The research team set out to determine whether the presence of this protein predicted which treatment would best prolong a patient’s life. They found that patients who tested positive for the protein responded best to taxane-based chemotherapy while those who tested negative for the protein responded best to hormone-targeting therapy with drugs called androgen-receptor signaling (ARS) inhibitors. These are the two most widely used drug classes to treat advanced prostate cancer. (more…)
Author Interviews, Cancer Research, Testosterone / 19.07.2018

MedicalResearch.com Interview with: Traver Wright, Ph.D. Research Assistant Professor Department of Health and Kinesiology Texas A&M University College Station, TX MedicalResearch.com: What is the background for this study?   Response: Many cancer patients suffer from a loss of body mass known as cachexia which results in not only a loss of fat, but a debilitating loss of muscle mass and function. This cachexia negatively impacts patient mobility and quality of life, and can also reduce their eligibility to undergo treatments such as radiation and chemotherapy.  Despite the profound negative consequences of cachexia, there are no established therapies to directly address this debilitating loss of body mass during treatment. In this National Cancer Institute funded double-blind, placebo-controlled study we examined the effectiveness of 7 weeks of treatment with the muscle-building hormone testosterone to preserve the body condition of men and women with cervical or head and neck cancer.  Twenty-one patients received weekly injections of either placebo or testosterone.  Over the 7 weeks of treatment, patients were monitored for changes in body composition, activity level, physical ability, and questionnaires regarding quality of life and well-being. (more…)
Author Interviews, Cancer Research, Lancet / 10.07.2018

MedicalResearch.com Interview with: Paul Lyon DPhil, MRCS Academic Clinical Fellow in Radiology Oxford University Hospitals NHS Foundation Trust Oxford, UK MedicalResearch.com: What is the background for this study? What are the main findings? Response: Delivering therapeutic doses of systemic chemotherapy to solid tumours, whilst ensuring side effects remain tolerable, has a presented a long-standing and unsolved challenge in oncology. With the advent of smart nanomedicines for clinical use, such as Lyso-Thermosensitive Liposomal Doxorubicin (LTLD, ThermoDox®, Celsion, USA), which has been formulated to release its doxorubicin content at 2.5°C above body temperature, there is now opportunity for targeted tumour therapy in combination with therapeutic devices. Much like a magnifying glass can focus energy from the sun to burn a hole in paper, ultrasound can be focused deep within the body to induce therapeutic effects in tumours, including ablation, hyperthermia and other bioeffects. Since its inception in the 1940s, focused (or therapeutic) ultrasound has evolved and is now FDA-approved for a variety of indications including ablation of several tumour types, virtue of being safe, non-invasive and non-ionising. Building on decades of preclinical research efforts worldwide, the TARDOX study is the first clinical trial to attempt triggered drug delivery to a target tumour non-invasively using an external focused ultrasound device. This phase 1 study which ran between March 2015-March 2017 in Oxford, UK, treated 10 patients with inoperable primary or secondary liver tumours which were either stable or refractory to previous chemotherapies. In each patient, a single intervention under general anaesthetic was performed during which a selected liver tumour was targeted and gently heated with focused ultrasound following an intravenous infusion of LTLD. Biopsies were used to determine the quantity of intratumoral doxorubicin before and after the ultrasound exposure.  (more…)
Author Interviews, Cancer Research, Nutrition / 29.06.2018

MedicalResearch.com Interview with: Ulrich Pfeffer, PhD Head of the Functional Genomics lab IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro Genova, Italy  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Curcumin is well known as a dietary integrator and in alternative medicine. Many previous studies showed its anti-cancer and many other beneficial activities. We and others had shown that these activities rely on its ability to reduce inflammation, which is an important factor in cancer development. This activity had also been described in much detail. It appears that curcumin inhibits the master regulator of the inflammatory program, the so called Nuclear factor kappa B, NFκB. In the present study, we asked whether Curcumin also affects tumor cell metabolism and if so, how. We show that curcumin inhibits a central enzyme of the cell metabolism, the ATP-Synthase, that stands at the end of the chain that burns sugar and produces energy. In tumor cells, this also leads to the production of reactive oxygen species, ROS, that kill the cancer cell. (more…)
ASCO, Author Interviews, Cancer Research, Technology / 22.06.2018

MedicalResearch.com Interview with: Alexandra Urman, MPH Clinical Research Manager Clinical Development IBM Watson Health  MedicalResearch.com: What is the background for this study?  Response: Cancer statistics show only 3-5% of cancer patients participate in clinical trials although up to 20% may be eligible. Dr. Tufia Hadad, a medical Oncologist at the Mayo Clinic in Rochester, Minnesota sought to address this issue and spearheaded a project conducted at the Rochester facility in collaboration with IBM Watson Health. The objective was to determine if the use of cognitive computing increased clinical trial enrollment and screening efficiency in the breast cancer clinic. Watson for Clinical Trial Matching (CTM) is a cognitive system which utilizes natural language processing to derive patient and tumor attributes from unstructured text in the electronic health record that can be further used to match a patient to complex eligibility criteria in trial protocols. (more…)
Author Interviews, Biomarkers, Cancer Research, JAMA, UCSD / 15.06.2018

MedicalResearch.com Interview with Aaron Goodman, MD Hematologist/Medical Oncologist Assistant Professor of Medicine UC San Diego Health  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Response rates to PD-1/PD-L1 blockade in solid tumors are reported at 10-20%.  Remarkably, response rates of 65% to 87% have been reported in patients with refractory classical Hodgkin lymphoma treated with checkpoint inhibitors. In nodular sclerosing Hodgkin lymphoma, amplification of the chromosomal region 9p24.1, which contains the genes PD-L1 (CD274), PDCD1LG2 (PD-L2)and JAK2, is directly correlated with increased expression of these proteins on Reed–Sternberg cells. Overall, 105 of 108 (97%) biopsies from patients with newly diagnosed classical Hodgkin lymphoma have increased PD-L1 and PDCD1LG2 copy numbers.  The prevalence and utility of PD-L1amplification as a response biomarker to PD-1/PD-L1 blockade is unknown in other tumors. We sought to determine the prevalence and utility of PD-L1 amplification as a response biomarker to PD-1/PD-L1 blockade in solid tumors.  (more…)
Author Interviews, Cancer Research, Genetic Research, Nature, Prostate Cancer / 13.06.2018

MedicalResearch.com Interview with: Fredrick R. Schumacher, PhD, MPH. Associate Professor, Department of Population & Quantitative Health Sciences Case Western Reserve University Cleveland MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Our study examines the genetic underpinnings of prostate cancer initiation using technology to test variants across the genome. Our study focused on men of European ancestry and included over 80,000 men with prostate cancer and 60,000 men without disease. We discovered 63 novel genetic variants associated with prostate cancer risk, which increases our knowledge of prostate cancer genetic risk factors by more than 60%. A genetic risk score created from the combination of 163 new and known prostate cancer risk variants revealed men with the highest genetic risk score are nearly seven times more likely to develop disease compared to the average man. Additionally, men with the lowest genetic risk score have a 85% risk reduction of developing prostate cancer compared to the average. Lastly, these new discoveries uncover several biological mechanisms involved in the initiation of prostate cancer. (more…)
ASCO, Author Interviews, Cancer Research / 07.06.2018

MedicalResearch.com Interview with: Axel Le Cesne, MD Institute de Cancerologie Gustave-Roussy Villejuif, France MedicalResearch.com: What is the background for this study? What are the main findings? Response: With the exception of a study in translocation-related sarcomas (TRS) (Kawai, TLO 2015), trabectedin was never compared to best supportive care (BSC) in a randomized study in patients with all STS histotypes. This trial required by French Health Authorities in 2014. The tumor control rate after 6 cycles of trabectedin is similar (30%) to previous study in French referral centers (T-DIS trial, Le Cesne, Lancet Oncol 2015) evaluating trabectedin in all subtypes of STS. As already reported, trabectedin was well tolerated with no cumulative toxicities This study met its first endpoint as a preplanned PFS analysis showed a significant improvement in median PFS with trabectedin  over BSC in patients with pretreated ASTS including multiple histologies (HR: 0.39). A major impact of trabectedin was observed in the L-STS cohort (liposarcomas and leiomyosarcomas) with a median PFS of 1.4 months in the BSC arm and 5.13 m (HR: 0.29, p<0.0001) in the trabectedin arm. respectively). The benefit observed with trabectedin in the L-STS cohort of patients is similar to those observed in the US trial in the same population (4.2 vs 1.5m for DTIC) (Demetri, JCO 2016) and in the Japanese trial mentioned above (5.8 vs 0.9m for BSC) (Kawai, TLO 2015) After the crossing over allowed by the protocol (trabectedin for patients progressing in the BSC arm), safety and efficacy profiles of trabectedin remains similar. We did not observe a difference in terms of OS between the two arms, probably due to the cross-over planned by the protocol.  (more…)
ASCO, Author Interviews, Dermatology, Melanoma, Merck, University of Pittsburgh / 05.06.2018

MedicalResearch.com Interview with: Dr. Diwakar Davar, MD Assistant Professor of Medicine Division of Hematology/Oncology University of Pittsburgh  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The optimal surveillance strategy to detect recurrence in cutaneous melanoma remains elusive. Risk of recurrence increases with higher stage, and is especially high for patients with stage IIIC disease. Although consensus guidelines agree on surveillance imaging for high-risk (stage IIB-IIIC) MEL, there is no consensus regarding optimal frequency/modality in these patients. NCCN guidelines suggest chest radiography (CXR) at 6- to 12-month intervals for stage IA-IIA melanoma  patients; although this is controversial. There exists a great deal of practice variation in the surveillance of these patients. (more…)
Author Interviews, Global Health, JAMA, Leukemia / 21.05.2018

MedicalResearch.com Interview with: Andrew J. Cowan, MD Seattle Cancer Care Alliance Division of Medical Oncology University of Washington, Seattle MedicalResearch.com: What is the background for this study? What are the main findings?   Response: Multiple myeloma (MM) is a plasma cell neoplasm with substantial morbidity and mortality. A comprehensive description of the global burden of multiple myeloma is needed to help direct health policy, resource allocation, research, and patient care. Myeloma cases and deaths increased from 1990 to 2016, with middle-income countries contributing the most to this increase. Treatment availability is very limited in countries with low socioeconomic development. (more…)
Author Interviews, Cancer Research, JAMA, Yale / 15.05.2018

MedicalResearch.com Interview with: Jeremy O'Connor, MD Section of General Internal Medicine Department of Internal Medicine Postdoctoral Fellow, National Clinician Scholars Program Yale University MedicalResearch.com: What is the background for this study?   Response: There has been a lot of enthusiasm for the use of novel therapies in cancer care, and in particular for novel anticancer agents known as immune checkpoint inhibitors. But very little is known about how quickly providers have adopted immune checkpoint inhibitors into clinical practice. Existing studies suggest, in fact, that the process of clinical adoption is slow, with conventional wisdom holding that it takes an average of 17 years for new evidence to change practice. Our study evaluated whether the adoption of novel therapies might be much faster in certain contexts with the early use of immune checkpoint inhibitors as a notable example. (more…)
Author Interviews, BMJ, Cancer Research, Gender Differences / 14.05.2018

MedicalResearch.com Interview with: “Faecal Coliforms analysis” by SuSanA Secretariat is licensed under CC BY 2.0Dr. Mahiben Maruthappu Public Health Registrar MedicalResearch.com: What is the background for this study? What are the main findings? Response: Gender disparities in the fields of science and technology have been documented, and  it becomes increasingly apparent at higher levels of seniority. In this analysis, we found a quantifiable difference in cancer research funding awarded to female principle investigators compared to male principle investigators (PIs). Across all cancer research funding grants that we identified, male PIs received 3.6 times the total investment value, and 1.6 times the average award value compared with their female counterparts.  (more…)
AACR, Author Interviews, Genetic Research / 18.04.2018

MedicalResearch.com Interview with: Ed Liu, M.D President and CEO The Jackson Laboratory (JAX) MedicalResearch.com: What is the background for this study? What are the main findings? Response: A few years ago we and others identified a complex genomic instability profile commonly found in the genomes of breast, ovarian and endometrial carcinomas, which is characterized by hundreds of isolated head-to-tail duplications of DNA segments, called tandem duplications. We refer to this configuration as the tandem duplicator phenotype, or TDP. In this study, we perform a meta-analysis of over 2,700 cancer genomes from over 30 different tumor types and provide a detailed description of six different types of TDP, distinguished by the presence of tandem duplications of different sizes. Collectively, these profiles are found in ~50% of breast, ovarian and endometrial carcinomas as well as 10-30% of adrenocortical, esophageal, stomach and lung adeno-carcinomas. We show that distinct genetic abnormalities associate with the distinct TDPs, clearly suggesting that distinct molecular mechanisms are driving TDP formation. In particular, we provide strong evidence of a casual relationship between joint abrogation of the BRCA1 and TP53 tumor suppressor genes and the emergence of a short-span (~11 Kb) TDP profile. We also observe a significant association between hyper-activation of the CCNE1 pathway and TDP with medium-span (~230 Kb) tandem duplications, and between mutation of the CDK12 gene and medium- and large-span TDP (coexisting 230 Kb and 1.7 Kb tandem duplications). Importantly, we find that different forms of TDP result in the perturbation of alternative sets of cancer genes, with short-span TDP profiles leading to the loss of tumor suppressor genes via double transections, and larger-span TDP profiles resulting in the duplication (i.e. copy number gain) of oncogenes and gene regulatory elements, such as super-enhancers and disease-associated SNPs.  (more…)
AACR, Author Interviews, Cancer Research / 17.04.2018

MedicalResearch.com Interview with: Mark E. Hatley, M.D., Ph.D. Assistant Member Molecular Oncology Division, Department of Oncology St. Jude Children's Research Hospital Memphis, TN 38105 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma occurring in children. Tumors appear histologically and genetically as undifferentiated skeletal muscle and are thus thought to solely originate from early skeletal muscle cells. However, tumors occur throughout the body, including sites devoid of skeletal muscle. In addition, tumor location is a key feature of staging and 40% of patients develop RMS in the head and neck. Interestingly, head and neck muscle development is distinct from the development of trunk and limb muscle. Previously we described a model of rhabdomyosarcoma which occurred specifically in the head and neck and originated from non-muscle cells. In this study we investigated how normal development programs are hijacked to drive rhabdomyosarcoma location. We demonstrated that RMS can originate from immature blood vessel cells that lie in between muscle fibers specifically in the head and neck. During development, these cells are hijacked, and become reprogrammed into rhabdomyosarcoma rather than mature endothelial cells. These RMS cells express factors important in head and neck muscle development. Our findings highlight that cell of origin contributes to RMS location and may explain why a high proportion of RMS occurs in the head and neck.  (more…)
Author Interviews, Cancer Research, JAMA / 16.04.2018

MedicalResearch.com Interview with: Lindor Qunaj BSc MD'19 Medical student, Warren Alpert Medical School of Brown University Brown Center for Biomedical Informatics Providence, Rhode Island MedicalResearch.com: What is the background for this study? What are the main findings? Response: Our study was motivated by growing concerns that incomplete or delayed release of clinical trial data may put patients at risk of harm or suboptimal treatment and slow the pace of biomedical innovation. Especially in a field as rapidly evolving as oncology, complete and timely dissemination of clinical trial results is critical to the advancement of both patient care and scientific discovery. In an analysis of press releases from eight large pharmaceutical companies, we found that the median delay from presumed availability of Phase 3 trial data to peer-reviewed publication or public posting of results was 300 days. Studies reporting positive findings were published more rapidly than those with negative results. (more…)
Author Interviews, Cancer Research, JAMA, Johns Hopkins / 16.12.2017

MedicalResearch.com Interview with: Gonzalo Torga, MD Urology Department Johns Hopkins Hospital Baltimore, MD 21287 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Liquid biopsy is a new and noninvasive alternative to tumor tissue sequencing, and it is intended to specifically detect and sequence tumor DNA circulating in patients’ blood. The results are used to help guide oncologists to tailor the best treatment for patients at each point of their disease. Our research was initially aimed at finding the best commercial lab to test samples from metastatic prostate cancer patients. We wanted to make the best choice for our patients, so we started submitting the samples to both places at the same time to compare results. However, we found significant disparities in the results from identical patient samples submitted to two different commercial liquid biopsy providers, and we believed it would be important to share them with the oncology community. The two liquid biopsy panels compared were the Guardant360, from Guardant Health, Inc., which sequenced at least part of the coding sequences of 73 genes; and the PlasmaSELECT panel from Personal Genome Diagnostics, which sequenced coding segments of 64 genes.  Both laboratories were licensed by Clinical Laboratory Improvement Amendments (CLIA) and accredited by the College of American Pathologists (CAP), and report having high sensitivity (in this case, the ability to correctly identify mutations when they occur) and high specificity (the ability to correctly report as negative when those mutations are not present). The two companies differ in which genes, and regions within each gene, are covered. Just 25 of the 40 patients in the study had at least one genetic mutation reported within the overlapping genetic sequences covered by both companies. Even when the companies were analyzing DNA from the same blood drawn, their results rarely matched each other. When comparing results within the overlapping genetic sequences, the results from both companies completely matched for all the mutations reported in only 7.5 percent (3 of 40 patients) of cases. In 15 percent of the patients (6 of 40), both companies’ results matched for at least one of the reported mutations. In 40 percent (16 of 40) of the patients, no mutations reported that were potentially covered by both panels were detected by both companies. (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Genetic Research, JAMA / 15.12.2017

MedicalResearch.com Interview with: Annette S. Kim, MD, PhD Associate Professor, Harvard Medical School Brigham & Women's Hospital Boston MA 02115  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The recent debate on laboratory developed tests (LDTs) and FDA-approved companion diagnostics (FDA-CDs) has centered upon both the regulatory and performance aspects of LDTs and we, at the College of American Pathologists (CAP), had the data through our proficiency testing (PT) programs to address the latter point, performance that we wanted to share with the community.  We analyzed almost 7000 PT responses on three molecular oncology tests, those for BRAF, EGFR, and KRAS mutations, and found that both LDTs and FDA-CDs demonstrated excellent performance, with both test types exceeding 97% accuracy overall. The second key finding of the study was that more than 60% of all laboratories in our study that were using an FDA-CD kit report using it with modifications from the FDA-approved protocol.  These modifications in fact render these test LDTs.  These modifications appear to be driven by the exigencies of real day-to-day clinical practice that requires adapting the assays to meet the needs of a variety of clinical situations that may not be accommodated by the FDA-approved protocol.  These modifications include, for example, the testing of other tumor types that may carry targetable variants, different types of input specimen preparations available in pathology such as cytology smears or other fresh specimens rather than paraffin blocks, and availability of different methods of DNA quantification that those mandated by the FDA approval based upon pre-existing technologies in the laboratories.  In the clinical laboratory, we are always acutely aware that there is a patient awaiting this result. Therefore, we validate our assays to ensure that we can provide reliable and accurate results from our laboratory under as many varied clinical situations as possible. These data support that practice. (more…)
Author Interviews, Chemotherapy, Lung Cancer, Science / 24.07.2017

MedicalResearch.com Interview with: Prof. Gerhard Hamilton Department of Obstetrics and Gynecology Medical University of Vienna MedicalResearch.com: What is the background for this study? What are the main findings? Response: Small cell lung cancer (SCLC) is a highly aggressive tumor (15 % of all lung cancers) mainly of patients with high tobacco consumption which shows an extremely poor survival (< 5% 2-year survival rate). Unfortunately the low survival rates of advanced SCLC cases has not improved significantly during the last decades, with platinum drugs/etoposide and topotecan employed for first- and second-line chemotherapy, respectively. All kinds of new chemotherapeutics, targeted drugs and immunotherapies either failed or resulted in prolongation of survival of several months at best. SCLC responds well to first-line therapy but relapses within a short time as chemoradioresistant tumor. The failure of hundreds of registered studies seem to be linked to the lack of knowledge of the mechanism of resistance of SCLCs and proper ways to reverse the refractoriness. Small cell lung cancer is distinguished by excessive numbers of circulating tumor cells (CTCs) in advanced stages. CTCs contain the founder of metastasis and seem to constitute a highly chemoresistant cell population. Thus, we ware able to establish a panel of permanent CTC lines in vitro for the first time (8 SCLC lines so far from blood samples). Although CTCs were considered to be chemoresistant we detected that they are chemosensitive in vitro in form of single cell suspensions. However, all CTC lines developed spontaneously into large multicellular aggregates, termed tumorospheres, which grow up to 1-2 mm in size and exhibit high chemoradioresistance due to limited drug perfusion as well as content of quiescent and hypoxic cells. Resistance to irradiation seems to be caused by lack of oxygen, such limiting the generation of oxygen radicals. High resistance mediated by the occurrence of tumorospheres easily explains the failure of a large number of drugs - if one is not able to achieve a sufficient concentration of a drug in cancer cells and the cells are quiescent, the respective compounds will not be able to destroy the target cells, regardless of their chemical nature. (more…)