Author Interviews, Cancer Research, Heart Disease, Journal Clinical Oncology / 07.02.2016

MedicalResearch.com Interview with: Saro H. Armenian, DO, MPH Associate Professor Departments of Pediatrics and Population Sciences City of Hope Comprehensive Cancer Center Director of the Childhood Cancer Survivorship Clinic Duarte, CA     Medical Research: What is the background for this study? What are the main findings? Dr. Armenian: There are an estimated 14 million cancer survivors living in the U.S. today, and this number is expected to reach 19 million by 2024. Among these cancer survivors, nearly two-thirds will have survived more than five years beyond their cancer diagnosis, and two out of every five will be considered a ten-year survivor, contributing to a growing population of aging cancer survivors. Until now, very little was known about the cardiovascular health of adult long-term cancer survivors. For the current study, we relied on diagnosis/procedures routinely recorded in a large integrative healthcare system that includes racially/ethnically and socioeconomically diverse members who are broadly representative of the residents in Southern California. Cardiovascular outcomes were captured from a wide variety of healthcare delivery settings (inpatient and outpatient, primary and sub-specialty care). Importantly, cancer survivors included in the current study continued to receive their primary and subspecialty care within this system well-beyond their initial cancer diagnosis (5- and 10-year retention rate: 81% and 70%, respectively), providing us with reliable population-based estimates of long-term cardiovascular disease (CVD) risk. We found an up to 70% higher risk of CVD (ischemic heart disease, stroke, or cardiomyopathy/ heart failure) in patients diagnosed with breast, kidney, lung/bronchus, multiple myeloma, non-Hodgkin lymphoma, and ovarian cancer when compared with an age- sex- and zip-code matched non-cancer controls. Cancer survivors who had multiple modifiable risk factors such as hypertension, diabetes, dyslipidemia were at highest risk of developing cardiovascular disease  later in life, irrespective of cancer diagnosis. Importantly, cancer survivors who developed CVD were significantly more likely to die from all causes when compared to cancer survivors who did not develop CVD. While the reasons for these findings are not clear, it is possible that the presence of CVD can markedly diminish treatment options or planned duration of therapy at the time of cancer recurrence, thus compromising the optimal long-term management of a cancer patient. (more…)
Author Interviews, Cancer Research, Heart Disease, JAMA, Pharmacology / 06.02.2016

MedicalResearch.com Interview with: Jonathan Douxfils Pharm.D. - Ph.D. Research assistant Faculty of Medicine - Department of Pharmacy NAmur Research Institute for LIfe Sciences (NARILIS) Namur Thrombosis and Hemostasis Center (NTHC) Medical Research: What is the background for this study? What are the main findings? Dr. Douxfils: We decided to perform this study based on the release of the FDA regarding the risk of arterial occlusive events associated with ponatinib. We then hypothesize that the risk was not only restricted to ponatinib but also to other TKIs. This study shows that dasatinib, nilotinib and ponatinib increase the risk of vascular occlusive events compared to imatinib. Medical Research: What should clinicians and patients take away from your report? Dr. Douxfils: We suggest that patients treated with these molecules should be more frequently monitored, i.e. by an intensive support of associated comorbidities. In addition, even if they appear to have a better efficacy in terms of molecular response, new generation TKIs does not improve the overall survival at one year. As we have not access to individual data, it was impossible to clearly identify categories of patients for whom the risk of cardiovascular occlusive events is predominant. Therefore, the intensive monitoring proposed should be applied to all patients treated with these molecules. Regarding the choice of the therapy, the physician should certainly consider the goals of the treatment. For elderly patients, improving survival is the main objective and in this context, imatinib remains an excellent choice. For patients with a life expectancy greater than 10 years in whom we aim to achieve a deep molecular response to potentially reach a point of treatment cessation, dasatinib and nilotinib could be preferred. However, the choice of dasatinib or nilotinib as first-line treatments should involve a screening for potential risk factors such as diabetes, prior vascular occlusive events or any risk that could increase these adverse events. For second- and third-line treatments, the choice of the treatment has to be based on mutational analysis, previous adverse events, and the medical condition of the patient. Thus, in case of intolerance or resistance, the switch to one of the other TKIs approved for first-line therapy is an option. If treatment failure still occurs, a more potent TKI, i.e. bosutinib, is preferred. Importantly, ponatinib is reserved to patients with the T315I mutation and must be avoided in patients with good prognosis. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Genetic Research, Pediatrics, University of Pennsylvania / 04.02.2016

MedicalResearch.com Interview with: Dr. Adam C. Resnick, Ph.D Assistant Professor of Neurosurgery Faculty, Abramson Cancer Center Director of Children's Brain Tumor Tissue Consortium Division of Neurosurgery Director, CHOP/PENN Department of Neurosurgery Brain Tumor Tissue BiorepositoryDirector for Neurosurgical Translational Research, Division of Neurosurgery Children's Hospital of Philadelphia   Payal Jain, PhD Candidate Division of Neurosurgery, Children's Hospital of Philadelphia Department of Neurosurgery Cell and Molecular Biology Graduate Group Gene Therapy and Vaccines Program Perelman School of Medicine University of Pennsylvania Philadelphia, Pennsylvania   Medical Research: What is the background for this study? What are the main findings? Response: This study originates from our long-standing interest in studying pediatric low-grade gliomas (PLGGs), which are the most commonly diagnosed brain tumor in children. While several PLGGs have been found to harbor mutations/gene fusions driving the mitogen-associated protein kinase (MAPK) pathway leading to clinical trials testing MAPK inhibitors, these tumors remain poorly categorized and not enough is known about specific genetic mutations driving different tumor sub-types and the potential for specific targeted therapeutics. Our current study encompasses analysis of the largest combined genomic dataset of pediatric low-grade gliomas samples.  In doing this we, identified the MYB-QKI gene fusion, a non-MAPK related event, as the common genetic event driving a rare PLGG sub-type, called angiocentric gliomas. We have reported a novel tri-partite mechanism by which MYB-QKI mediates its oncogenic effect, this being the first report of a single gene rearrangement utilizing three different paths to cause cancer.
  • First, this gene rearrangement activates MYB, which is a proto-oncogene that is normally not expressed in the developed brain.
  • Second, we found that the rearrangement leads to translocation of QKI-related enhancers close to MYB’s promoters, thereby driving MYB-QKI expression in these tumors. Furthermore, MYB-QKI can also regulate its expression in a positive feedback loop.
  • Third, the tumor suppressor activities of QKI are disrupted in MYB-QKI. Such collaboration of genetic and epigenetic dysregulation in a single genetic rearrangement has previously not been reported.
(more…)
Cancer Research / 03.02.2016

MedicalResearch.com Prof. Norbert Stefan, MD Department of Molecular Epidemiology German Institute of Human Nutrition Potsdam-Rehbruecke Nuthetal, Germany MedicalResearch: What is the background for this study? Prof. Stefan: Cardiovascular disease, type 2 diabetes, and cancer are among the most important causes of morbidity and mortality worldwide. Although the body mass index and waist circumference are established variables that help to predict the risk of these disease, adult height also predicts mortality independently of adiposity measures. However, compared to these risk factors, it has been somewhat neglected in clinical practice. Based on the finding that in recent decades the height of children and adults has steadily increased throughout the world, the question arises whether this secular trend in height might be a marker of a yet not well understood mechanism that affects not only stature, but also the development of cardiometabolic disease and cancer.  MedicalResearch: What are the main findings? Prof. Stefan: We summarized and interpreted data from different areas of research and also could provide some novel data to better understand the causes of the worldwide increase in height and its relationships with cardiometabolic disease and incidence of cancer. There is strong epidemiological evidence that tall people, in comparison to short people, have a lower risk of cardiovascular disease and type 2 diabetes but have a higher cancer risk. Per 6.5 cm in height the risk of cardiovascular mortality decreases by six percent, but cancer mortality, by contrast, increases by four percent. We suspect that the increase in body height is a marker of overnutrition of high-calorie food rich in animal protein during different stages of growth. Thus, already in utero, lifelong programming might take place that until now has mainly been established for the insulin-like growth factor 1 and 2 and the IGF-1/2 system. Among other consequences, activation of this system causes the body to become more sensitive to insulin action, thus positively influencing the lipid metabolism. Accordingly, our new data show that tall people are more sensitive to insulin and have lower fat content in the liver, which may explain their lower risk for cardiovascular disease and type 2 diabetes. However, this activation of the IGF-1/2 system and other signaling pathways may be related to an increased risk of certain cancers, especially breast cancer, colon cancer, and melanoma because cell growth is permanently activated. (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Lancet, Pediatrics, Radiation Therapy / 02.02.2016

MedicalResearch.com Interview with: Dr. Torunn Yock, MD Director, Pediatric Radiation Oncology Associate Professor, Harvard Medical School Radiation Oncology Quality Assurance Massachusetts General Hospital, Proton Center Boston, MA Medical Research: What is the background for this study? Dr. Yock: Proton radiotherapy is a highly targeted form of radiation therapy that can spare normal tissues better than standard x-ray/photon based radiotherapy. Because, all side effects from radiotherapy come from radiation dose to normal healthy tissues, it is widely believed that proton radiotherapy has great potential to mitigate the side effects of treatment, both acute and long term side effects. There have been many planning studies that show that proton radiation can achieve a more highly conformal dose distribution and appear to spare 50% or more normal tissue from unnecessary irradiation.  However, there have been only a handful of retrospective studies that report disease control and side effects of treatment. While the technology looked promising, the definitive clinical data has been lacking to date. Because of this lack of clinical outcome data, the role and benefit of proton radiotherapy has been a subject of great debate in the oncology community.  Critics assert that proton radiotherapy is expensive and unproven and therefore a leading culprit in escalating costs of oncologic health care. Proponents assert that when used in the appropriate patient setting, the margin of benefit in terms of improved health outcomes, outweighs the increased cost of treatment. We embarked on this study to answer help answer the call for prospectively collected clinical outcome data to better define the most appropriate role for proton radiotherapy. Importantly, this study addresses both disease control and side effects of treatment in a pediatric medulloblastoma cohort of children. Medical Research: What are the main findings? Dr. Yock: This study shows that disease control in the pediatric medulloblastoma population is very much the same as that which is achieved by photon based radiotherapy treatments. However, more importantly, late side effects commonly attributed to radiotherapy such as neurocognitive decline over time and hearing loss appear to be improved compared with published photon treated cohorts of pediatric medulloblastoma patients.  Additionally, adverse late side effects on the cardiopulmonary, GI, and reproductive systems were essentially eliminated. (more…)
Author Interviews, BMJ, Colon Cancer, Gastrointestinal Disease, Global Health / 31.01.2016

MedicalResearch.com Interview with: Dr. Melina Arnold Section of Cancer Surveillance International Agency for Research on Cancer Lyon, France MedicalResearch.com: What is the background for this study? What are the main findings?  Dr. Arnold: In this study, we looked at patterns and time trends in the incidence in and mortality from colorectal cancer on the global scale. In the analyses, we used data from the Globocan database, Cancer Incidence in Five Continents, both hosted by the International Agency for Research on Cancer (IARC), and the World Health Organisation mortality database. We documented a ten-fold variation in colorectal cancer incidence and mortality rates worldwide. We also found distinct gradients across human development levels, meaning that changes in patterns and trends of this cancer could be linked to economic development and that the adoption of a Western lifestyle may have a role. While incidence and mortality rates are on the increase in many countries in socioeconomic transition, stabilizing or decreasing trends are seen in highly-developed countries where rates remain among the highest in the world. These observations point to widening disparities and an increasing burden in transitioning countries. (more…)
Author Interviews, Cancer, Colon Cancer, Surgical Research / 29.01.2016

More on Colon Cancer on MedicalResearch.com MedicalResearch.com Interview with: Samantha Hendren, MD, MPH Associate Professor of Surgery Colorectal Surgery University of Michigan  Medical Research: What is the background for this study? What are the main findings? Response: We studied colorectal cancer nationally, and found that about 1 in 7 colorectal cancer patients in the U.S. (that is, 14.7%) is diagnosed before the age of 50.  We also found that these younger colorectal cancer patients were diagnosed when their cancers were more advanced (higher “stage”, meaning more of them had spread to lymph nodes and/or to other organs).  Part of the reason for this is that these young patients are often diagnosed only after their cancers start to cause symptoms such as anemia, bowel bleeding or a blockage in the colon. The age of 50 is when screening for colorectal cancer is started in the U.S.  This study means that a pretty large proportion of colorectal cancers are  happening in people who are too young to receive screening tests.  To put this in context, breast cancer screening often begins at age 40, and less than 5% of invasive breast cancers occur in women under that age. Our study found that about 15% of colorectal cancers are diagnosed before the screening age of 50. Fortunately, the young patients with colorectal cancer do a little better than you might predict, knowing that they are diagnosed at a worse cancer “stage”.  For the young patients under 50, about 68% survived 5 years, while about 67% of the patients 50 and older survived 5 years.  It looks like patients’ young age helps them in their cancer treatment and survival; our study found that treatment may be a bit more aggressive in the younger patients. (more…)
Author Interviews, Cancer Research, Genetic Research, PNAS / 28.01.2016

MedicalResearch.com Interview with: Nina Bhardwaj, MD, PhD and Director of Immunotherapy and professor of Hematology and Medical Oncology Benjamin Greenbaum, PhD Assistant Professor The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai   Medical Research: How did the discovery of the group of non-coding RNA molecules in cancer cells that sets off an immune response come about? Dr. Greenbaum: Our work is a collaboration between my lab, which is computational, and the Bhardwaj lab, focused on cancer immunology. I had previously made the observation that certain RNA viruses were avoiding certain motifs, such as CpG dinucleotide containing motifs, and the Bhardwaj lab tested whether those motifs could set off an immune response. Recent work had shown that tumors transcribe unusual RNA with immunological consequences, so we investigated whether the same sort of approaches we had used for viral RNA worked here. Dr. Bhardwaj: It has recently become clear that, due to epigenetic alterations, tumors transcribe non-coding RNAs that are typically silenced. Often such RNA emanates from the “dark matter” genome. Many of these regions consist of repetitive elements and endogenous retroelements that are rarely transcribed in normal tissue. At the same time, due to immunotherapy, understanding the role of the immune system and immune activation in tumors has become critically important. The activation of specific elements of the innate immune system in a tumor may have either beneficial or detrimental effects for patients. Moreover, recent work has suggested that endogenous element activation can lead to improved immunotherapy outcomes. Therefore, it is critically important to understand the nature of innate immune activation in tumors and what triggers are responsible for these responses. We have been developing methods to detect abnormal patterns in viral RNA that may indicate activation of the innate immune system. We have found that patterns of motif usage avoided in the evolution of viruses, such as influenza, indicate RNA features that provoke an innate immune response. The innate immune system is capable of sensing motifs in viruses. We tested directly whether these avoided patterns are immunostimulatory. Medical Research: What are the main findings? Dr. Bhardwaj: We used a novel quantitative approach, derived from methods in statistical physics, to characterize all of the non-coding RNA transcribed by normal tissue and compared them to the non-coding RNA found in tumors. We found that while the non-coding RNA transcribed in normal tissue displays patterns of motif usage consisting with that of coding RNA, the RNA transcribed in tumors, yet rarely found in normal tissue, can have motif usage more typically associated with viral and bacterial genomes. We predicted a handful of such RNA are immunostimulatory and validated this prediction in antigen presenting cells. We then showed that this sensing may come from a subset of the innate immune system associated with pathogen RNA sensing. We called these RNA “i-ncRNA”, for immunostimulatory non-coding RNA. (more…)
Author Interviews, Cancer Research, Infections / 27.01.2016

MedicalResearch.com Interview with: Yvonne Kapila, DDS, PhD Professor, Division of Periodontics Department of Periodontics and Oral Medicine University of Michigan School of Dentistry Ann Arbor, MI   Medical Research: What is the background for this study? What are the main findings? Dr. Kapila: Our research showed that the preservative nisin induces cancer cell death. When tested on normal control cells to see if they were affected, the control cells were not affected. Thus, the most recent project began in order to find out more details as to why this occurred. We used a cancer mouse model (head and neck cancer) to show that nisin can retard tumor growth and extent the life of these mice. Another thing that we published about the preservative is nisin’s role on biofilms. Biofilms are communities of bacteria that can cause diseases. Nisin has been tested in bacterial biofilms that contain bacteria that cause gum disease and dental decay and nisin has been found to be effective in this setting as well. In laboratory settings, nisin is also cytotoxic to superbugs, including the most resistant bugs found in hospitals, and therefore nisin holds promise for several therapeutic applications. (more…)
Author Interviews, Cancer Research, Genetic Research, Personalized Medicine, UCLA / 24.01.2016

MedicalResearch.com Interview with: Dr. Chirag Patil, MD American Board Certified Neurosurgeon Brain & Spine Tumor Program Lead Investigator, Precision Medicine Initiative Against Brain Cancer Program Director, Neurosurgical Residence training program Director, Center for Neurosurgical Outcomes Research Cedars-Sinai Medical Center, Los Angeles, California MedicalResearch.com Editor’s note: Dr. Patil’s research is focused on developing a method of personalized cancer treatment through the harnessing of genome wide mutational analysis of a specific patient’s cancer. MedicalResearch.com: Would you tell us a little about yourself and your research interests? Dr. Patil: I am a Stanford-trained, Board Certified Neurosurgeon and cancer researcher at Cedars-Sinai Medical Center in Los Angeles, California. I primarily focus on the care of patients with malignant brain tumors, particularly glioblastomas. I received my undergraduate degree from Cornell, followed by a medical degree from the University of California, San Francisco (UCSF), where I was a Regent’s scholar. I completed a residency in neurosurgery and a fellowship in stereotactic radiology at Stanford University. I also have a master’s degree in epidemiology with a focus on clinical trial design and mathematical modeling from Stanford. MedicalResearch.com: Can you tell us about some of your research interests? Dr. Patil: I am keenly interested in and focused on developing precision science-powered novel brain tumor therapies, immuno-therapies, and patient-centered “big data” outcomes research. I lead the recently-funded Cedars-Sinai Precision Medicine Initiative Against Brain Cancer, which utilizes tumor genomics to build a mathematical computer model, i.e., a virtual cancer cell of each patient’s unique tumor. The White House and several other stakeholders have taken keep interest in this research initiative as an example of a leading precision medicine program. (more…)
Author Interviews, HPV, JAMA / 22.01.2016

More on HPV on MedicalResearch.com  MedicalResearch.com Interview with: Ilir Agalliu, M.D., Sc.D. Assistant Professor, Department of Epidemiology & Population Health and Department of Urology Albert Einstein College of Medicine Jack and Pearl Resnick Campus Bronx, NY Medical Research: What is the background for this study? Dr. Burk: We performed this study since we had previously detected an unusually high prevalence of HPV types found on the skin and skin cancers in the oral cavity in addition to HPV16 and other high-risk (HR) types (as defined by their association with cervix cancer) (see Journal of Infectious Diseases 204:787, 2011). We wished to determine if these types were associated with risk of head and neck cancers (HNSCCs). In addition, we wished to determine if HPV detection preceded the diagnosis of HNSCCs and might serve as a biomarker. Currently there are no good screening tests for HNSCC. Dr. Agalliu: To-date, there have been no prospective studies examining the temporal relationship between oral HPV detection and risk of head and neck squamous cell carcinoma (HNSCC). In this manuscript we examined prospectively associations between detection of a wide spectrum of oral HPVs (alpha, beta and gamma) with incident HNSCC in a nested case-control study among ~100,000 participants who provided mouthwash samples in the American Cancer Society-CPS II cohort and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Dr. Agalliu: Oral HPV16 detection, which preceded cancer development on average for 4 years, was associated with a 22-fold increased risk for incident oropharyngeal cancer. Detection of other oral HPVs (beta1 HPV5, and gamma11 and 12 species) were associated with a 3.3 to 5.5-fold higher risk of  head and neck squamous cell carcinoma after adjustment for smoking, alcohol and HPV16. Associations of beta and gamma HPVs, which have been identified in the skin, with risk of HNSCC suggest a broader role for HPVs in HNSCC etiology. (more…)
Author Interviews, Cancer Research, PNAS / 21.01.2016

MedicalResearch.com Interview with: Dr. Elizabeth Murchison Menzies Institute for Medical Research University of Tasmania Save the Tasmanian Devil Program Tasmanian Department of Primary Industries, Parks, Water and the Environment Hobart Australia Department of Veterinary Medicine University of Cambridge, Cambridge UK Medical Research: What is the background for this study? Dr. Murchison: Transmissible cancers are cancers that can be transmitted between individuals by the transfer of living cancer cells. Transmissible cancers emerge only very rarely in nature, and until now only three examples were known. One of the three known naturally occurring transmissible cancers affects Tasmanian devils, the world’s largest carnivorous marsupial. This disease, which causes disfiguring facial tumours, was first observed in the late 1990s, and since then the disease has spread widely through the Tasmanian devil population. This transmissible cancer first emerged as a cancer in a single individual Tasmanian devil that probably lived about 30 years ago; this devil’s cancer cells have continued to survive by transmitting between hosts by biting. Medical Research: What are the main findings? Dr. Murchison: In late 2014, routine monitoring of the Tasmanian devil population led to the discovery of a male devil with facial tumours that resembled the known Tasmanian devil transmissible facial cancer. However, genetic analysis of this tumour indicated that the tumour in this devil was derived from a second transmissible cancer that was genetically unrelated to the first transmissible cancer in this species. Indeed, the genetic profile of this second cancer indicated that it had originally emerged from a male animal. This second cancer has subsequently been found in nine additional devils in the same part of Tasmania. (more…)
ASCO, Author Interviews, Cancer Research, Lymphoma / 18.01.2016

More Cancer Research on MedicalResearch.com MedicalResearch.com Interview with: Erin E. Hahn, PhD, MPH Research Scientist Southern California Permanente Medical Group Kaiser Permanente Research Department of Research & Evaluation Pasadena, CA 91101 Medical Research: What is the background for this study? Dr. Hahn:  Adolescent and young adults, or AYAs, who are diagnosed and treated for Hodgkin lymphoma have very high overall survival rates. However, these patients are at high risk for short and long term health issues related to their cancer treatment, including cancer recurrence, cardiac and pulmonary problems, and developing new primary cancers. Some of these issues arise during treatment and persist over time, called long-term effects, and some develop years later, called late effects. Evidence and consensus based guidelines are available from organizations like the National Comprehensive Cancer Network and the Children’s Oncology Group to help manage the post treatment care of  Adolescent and young adults Hodgkin lymphoma survivors. Examining adherence to guidelines is an important part of high quality care, and can help us find and address gaps in care. Guideline recommended care for these patients includes: oncology visits, imaging and labs, preventive care, counseling and education, risk based screening for late effects. Risk-based screening is based on a patient’s treatment. The type of health screening a patient needs is determined by the treatment exposure they had, such as certain types of chemotherapy or high-dose radiation that have known late effects  Medical Research: What are the main findings? Dr. Hahn: For this pilot study, I was interested to see if post-treatment  Adolescent and young adults Hodgkin lymphoma patients in an integrated health care system received recommended short and long term care. The study setting is Kaiser Permanente Southern California (KPSC). KPSC provides care for almost 4 million members with 14 medical centers, and they have a long-standing electronic medical record. For our population, we included AYA patients diagnosed with classical Hodgkin lymphoma between 15 and 39 years of age, diagnosed between 2000 and 2010. We wanted to find patients who were diagnosed, treated, and followed for at least 2 years within this single system. We have a sample of 354 patients, which is great. It has been traditionally difficult to find and follow these patients/obtain accurate medical information that isn’t only self-report data. We were able to extract chemotherapy, radiation, and other care details from the electronic medical record. We first looked at receipt of short term recommended care, within the first year after treatment had ended. We looked specifically at oncology visits, use of recommended CT scan and lab tests, and preventive care, such as the flu vaccine. The great majority of patients had the recommended oncology visits, CT scan, and lab tests. However, receipt of the flu vaccine was lower, at 20%. When we looked at a composite measure of all 4 recommended services, only about half of the patients received all four recommended services within the first year after treatment. We also looked at use of a longer term recommended service for cardiac issues. Cardiac screening is recommended for patients who are 10 years out from their treatment and who received high-dose anthracyclines, plus radiation to the chest. This is the highest risk group for cardiac damage. Almost everyone received annual blood pressure screening, but only about 30% received screening with an electrocardiogram, echocardiogram, or MUGA scan. (more…)
Author Interviews, Cancer Research, Technology / 15.01.2016

More on Cancer Research on MedicalResearch.com MedicalResearch.com Interview with: Elena V. Batrakova, Ph.D. Associate Professor Center for Nanotechnology in Drug Delivery Division of Molecular Pharmaceutics Eshelman School of Pharmacy University of North Carolina at Chapel Hill Chapel Hill, NC  Medical Research: What is the background for this study? What are the main findings? Dr. Batrakova: Deep down I was always was fascinated by the ability of biological systems to deliver various compounds to the disease sites. I believe, we have a lot to learn from living things. For example, immune cells, macrophages can feel inflammation and travel to this sited to deal with the problem, for example, kill bacteria, virus, or regenerate and support dying cells. So, when I realized that specific and targeted transport of therapeutics to cancer cells is very difficult task, I turned to nature. Exosomes are naturally occurring vesicles (bubbles) that offer distinct advantages that uniquely position them as highly effective drug carriers. They consist of cellular membranes with multiple sticky proteins on their surface. Exosomes by nature specialize in cell-cell communication and provide an approach for the delivery drugs to target disease sites. Plus, exosomes released by patient’s white blood cells are not immunogenic, because they are part of the immune system, so these tiny bubbles can be used for very precise and effective delivery of anticancer drugs to treat metastases, as well as primary tumors. (more…)
Author Interviews, Cancer Research / 14.01.2016

More on Protein Kinases on MedicalResearch.com MedicalResearch.com Interview with: Dr Angus Cameron Kinase Biology Laboratory Barts Cancer Institute at Queen Mary University of London and Professor Peter Parker Protein Phosphorylation Laboratory The Francis Crick Institute Medical Research: What is the background for this study? What are the main findings? Response: A particular family of candidate targets for cancer therapies (the three members of the protein kinase, or PKN, family) have been largely overlooked in terms of our understanding of their roles in normal biology and also in disease. Since any programme to develop new treatments is well informed by understanding the normal roles of the drug targets in non-tumour settings, our research teams ‘knocked-out’ these genes in a model mammalian system, in mice, and observed the effect. A key finding is that whilst two of the protein kinases, PKN1 and PKN3, are not necessary for mammalian development or adulthood, for PKN2 there is an absolute requirement in embryo development, but evidence of little requirement in adulthood. Our teams then analysed in some detail the genetics and pathology of the developmental defects for PKN2 knock-outs. This established the importance of PKN2 in mesenchymal cell survival and proliferation during development. Mesenchymal cells are dynamic contractile cells which provide structure and shape to the developing embryo. This finding has profound effects on multiple developmental events. Mesenchymal cells are also important in many connective tissue conditions, including fibrosis of the lungs, and in cancer where mesenchymal cells can support invasion of cancer cells into tissues. (more…)
Author Interviews, Cancer Research, JAMA, Transplantation / 11.01.2016

MedicalResearch.com Interview with: Sergio A. Acuna, MD Graduate Student at St. Michael's Hospital and IHPME University of Toronto Medical Research: What is the background for this study? Dr. Acuna: Solid organ transplant recipients are known to be at greater risk of developing cancers compared to the general population; however, because they are also at high increased risk of mortality from non-cancer causes, the risk of cancer morality in this population is unclear. As previous studies on this topic have reported disparate findings, the cancer mortality risk in this population remained uncertain. Medical Research: What are the main findings? Dr. Acuna: Our study provides conclusive evidence that solid organ transplant recipients are at increased risk of cancer mortality. Our findings demonstrate that solid organ transplant recipients are at increased risk of cancer death compared to the general population regardless of age, transplanted organ, and year of transplantation, and indicate cancer is a substantial cause of death in this population. (more…)
Author Interviews, Cancer Research, Heart Disease, Pediatrics / 07.01.2016

MedicalResearch.com Interview with: Daniel A. Mulrooney, MD, MS Cancer Survivorship Jude Children's Research Hospital TN 38105-3678 Medical Research: What is the background for this study? What are the main findings?  Dr. Mulrooney:  This is a cross-sectional analysis performed in the St. Jude Lifetime Cohort Study (SJLIFE), an ongoing study designed to facilitate longitudinal evaluation of health outcomes among adults previously treated for childhood cancer.  Following patients over the life spectrum can be challenging making it difficult to understand the long-term health effects of childhood cancer therapy.  Previous studies have relied on self-report, registry, or death certificate data.  Our study is novel because we clinically evaluated cancer survivors on the St. Jude campus and identified substantial, asymptomatic cardiac disease (cardiomyopathy, coronary artery disease, valvular disease, and conduction/rhythm disorders).
  • Cardiomyopathy was present in 7.4% of survivors and newly identified by screening in 4.7%.
  • Coronary artery disease was present in 3.8% of survivors and newly identified by screening in 2.2%.
  • Valvular disease (regurgitation or stenosis) was present in 28% of survivors and newly identified by screening in 24.8%.
  • Conduction or rhythm abnormalities were present in 4.4% of survivors and newly identified by screening in 1.4%.
The prevalence of these cardiac findings might be expected in an older population but not necessarily in this young adult (median age at time of study 31 years, range: 18-60) population.    (more…)
Author Interviews, Cancer Research, Genetic Research, Personalized Medicine, Technology / 06.01.2016

MedicalResearch.com Interview with: Dr Bissan Al-Lazikani Team leader in computational biology The Institute of Cancer Research London Medical Research: What is the background for the canSAR database? What are the main uses for the tool? Dr. Al-Lazikani: Drug discovery is a difficult, time consuming and expensive venture that frequently ends in late stage drug failures - especially in oncology. As with any complex venture, decisions throughout the drug discovery pipeline can be empowered by having access to the right information at the right time. But for drug discovery this means bringing together billions of experimental data from very diverse areas of science spanning genomics, proteomics, chemistry and more. We developed canSAR to help guide our own drug discovery efforts by integrating these huge, diverse data and by analysing the data and deriving hidden links and knowledge from them. This means that we can answer questions in minutes that would have taken weeks using previously available public resources. But, more importantly, canSAR analyses and links these data in a way that allows us  to derive knowledge that was hidden before. For example, one of the main ways canSAR is used is to help select the best druggable targets for drug discovery. Using canSAR we were able to uncover many druggable cancer proteins that were previously overlooked, and we are delighted to see that several of these proteins are now the subjects of drug discovery and development projects both by us and by others. We took the decision to make canSAR publicly and freely available because we believe that cancer drug discovery is a vast challenge that requires openness and data sharing worldwide. It has been embraced by the community is being used by tens of thousands of cancer scientists worldwide, both in academia and industry, to generate hypotheses for experiments and select targets for drug discovery. (more…)
Author Interviews, Breast Cancer, Cancer Research, Chemotherapy, JAMA / 24.12.2015

MedicalResearch.com Interview with: Filippo Montemurro, M.D. Director, Investigative Clinical Oncology (INCO) Fondazione del Piemonte per l'Oncologia Candiolo Cancer Institute (IRCCS) Torino, Italy Medical Research: What is the background for this study? Dr. Montemurro: The evaluation of treatment-related side effects is a critical step in cancer patient management. It is important in the clinical practice, where the decision to modify doses, omit administrations or establish supportive care measures is based on treatment tolerance and side effects severity and duration. It is also important in the context of clinical trials. In the latter setting, the mere information of the antitumor activity of a new drug or regimen under investigation is worth little if it not accompanied by an accurate reporting of the side effect profile. For this reason, over the years reference protocols to standardize the process of toxicity reporting in clinical trials have been established. The most recent and widespread is the Common Terminology Criteria for Adverse Events (CTCAE), that is issued and constantly updated by the National Cancer Institute. The CTCAE allows the description of the incidence and on the grade of severity on a scale ranging from 0 (no toxicity) to 5 (death due to that toxicity). Normally, the medical or nursing staff data collects information to fill in the CTCAE reports either by interviewing patients or extracting data from the clinical notes taken by physicians. The "indirectness" of this process has consequences that are becoming acknowledged for their potential implications. The incidence and severity of toxicities results often underestimated by doctors when their reports are compared with corresponding reports provided directly by patients without intermediaries (so called Patient reported outcomes-PRO). If this phenomenon is described in the context of clinical trials, it might occur to a greater extent also in the clinical practice, where the process of toxicity reporting is not mandated by a protocol and no reference standard is recommended. Based on these premises, we designed a study to pursue two aims;
  • the first was to assess whether a 10-item questionnaire derived by the CTCAE could be used by breast cancer patients receiving adjuvant chemotherapy after surgery in the daily clinical practice;
  • the second was to compare doctors and patients reports of toxicities at corresponding time-points.
Medical Research: What are the main findings? Dr. Montemurro: We administered the 10-item questionnaire after the first and third cycle of adjuvant chemotherapy to 601 women who had undergone surgery for breast cancer. To develop this questionnaire, CTCAE definitions of severity for each item (nausea, vomiting, constipation, anorexia, dysgeusia, diarrhea, fatigue, pain, paresthesia, and dyspnea) were translated into Italian and rephrased into statements. Patients were asked to choose the statement that best represented the worst experience with that side effect after the reference cycle of chemotherapy. At the same time-points, research nurses extracted information from the medical charts and reported them in paired doctor questionnaires. A total of 99% and 97% of the patient returned filled in questionnaires. Pairwise comparisons showed that doctors systematically underestimated both incidence and severity for all the side effects. Interestingly, comparison of the two patient questionnaires revealed temporal changes that were possibly related to the effect of prophylactic measures taken after the first cycle (i.e. reduction in vomiting, diarrhea and pain) or to cumulative toxicties (i.e. worsening dysgeusia and dyspnea). No such changes except for worsening dyspnea were observed comparing the two doctors questionnaires. Finally, we found a direct relationship between number of patients and magnitude of discrepancy in side effects reporting was observed, suggesting that the workload could be a factor influencing this phenomenon. (more…)
Author Interviews, Cancer Research, Colon Cancer, Cost of Health Care, JAMA, Social Issues, University of Michigan / 23.12.2015

MedicalResearch.com Interview with: Christine Veenstra MD Clinical Lecturer, Internal Medicine Medical Oncology University of Michigan Ann Arbor, MI  48109-5343 MedicalResearch: What is the background for this study? What are the main findings? Dr. Veenstra: Patients with cancer face many costs and incur financial burden as they go through diagnosis and treatment. For working patients, cancer diagnosis and treatment may come with the additional burden of time away from work, lost income, and even long-term job loss. Although 40% of US workers do not have access to paid sick leave, we hypothesized that availability of paid sick leave could reduce the need to take unpaid time away from work during cancer treatment and might therefore be associated with job retention and reduced personal financial burden. In a survey of over 1300 patients with Stage III colorectal cancer, we found that only 55% of those who were employed at the time of their cancer diagnosis retained their jobs. Working patients with paid sick leave were nearly twice as likely to retain their jobs compared with working patients who did not have paid sick leave. This held true even when controlling for income, education and health insurance. Furthermore, working patients without paid sick reported significantly higher personal financial burden than those who had paid sick leave available. (more…)
Author Interviews, Cancer Research, JAMA, Lung Cancer, Surgical Research / 23.12.2015

MedicalResearch.com Interview with: Dr Najib Rahman D Phil MSc MRCP Consultant and Senior Lecturer Lead for Pleural Diseases Oxford Centre for Respiratory Medicine Clinical Director, Oxford Respiratory Trials Unit Tutor in Clinical Medicine University College, Oxford Medical Research: What is the background for this study? Dr. Rahman : Up to TIME1, the evidence base behind optimal pleurodesis for malignant pleural effusion in terms of tube size and analgesia was poor. Optimal pleurodesis in this context is one which is successful (i.e. the patient needs no further pleural interventions for that malignant effusion), but occurs with the minimum discomfort. This is particularly important as the treatment intent in malignant effusion pleurodesis is palliative. This is the first adequately powered randomized trial to address two important issues in pleurodesis for malignant pleural effusion - that of whether NSAIDs reduce pleurodesis efficacy, and if smaller chest tubes (12F) are "as good as" larger chest tubes (24F) for pleurodesis success and in terms of pain. Medical Research: What are the main findings? Dr. Rahman : The main and somewhat surprising findings are that:
  1. NSAIDs given short term but at high dose do not impair pleurodesis - they are no better than morphine for pain control (in fact, they needed modestly more rescue medication), but can be freely used during malignant effusion pleurodesis with no fear of reducing pleurodesis success.
  1. Smaller tubes were marginally less painful than larger tubes - but this difference was not clinically very relevant
  1. Smaller tubes cannot now be said to be "as good as" larger tubes for malignant effusion pleurodesis. Our data shows that they failed in non-inferiority to larger tubes for pleurodesis success at 3 months. 
  1. Smaller tubes resulted in higher fall our rates, a higher incidence of not being able to administer talc and were associated with more complications during insertion .
(more…)
Author Interviews, Cancer Research / 21.12.2015

MedicalResearch.com Interview with: Amye Tevaarwerk, M.D. Assistant Professor of Medicine Hematology/Oncology Section University of Wisconsin School of Medicine and Public Health Carbone Comprehensive Cancer Center Wisconsin Institute for Medical Research (WIMR) Madison, WI  Medical Research: What is the background for this study? What are the main findings? Dr. Tevaarwerk: These patients were enrolled on a larger clinical trial known as the Symptom Outcomes and Practice Patterns study (SOAPP). SOAPP recruited breast, prostate, colon and lung cancer patients directly during outpatient oncology follow-up visits. All of the patients were recruited between May 2006 and May 2008. The parent study recruited 3123 patients, of these 680 patients had metastatic disease and 668 had employment data. Patients were asked if they were working and if there had been a change due to illness. We were able to compare those stably working with those who had changed to "no longer working" and look at factors that associated with this change (age, gender, cancer type, race/ethnicity, time since diagnosis, location of metastatic disease, type of treatment, performance status, number of metastases, symptom burden.) (more…)
Author Interviews, Cancer Research, Genetic Research, Nature / 17.12.2015

MedicalResearch.com Interview with: Dr. Li Ding PhD Director, Medical Genomics group McDonnell Genome Institute Department of Medicine Washington University in St. Louis St. Louis, Missouri Medical Research: What is the background for this study? What are the main findings? Dr. Li Ding:  Next-generation sequencing technologies have provided unprecedented opportunities for building a comprehensive catalog of point mutations, simple insertion and deletion mutations (indels) and structural variants in human cancers. Although significant progress has been made for documenting these common events through studies from individual research labs and large consortiums, there has been little progress in the discovery of complex indels after the transition from Sanger sequencing to NGS technologies.  It is well known in the scientific community that indel detection using short next generation sequencing reads is a challenging problem. Our study, for the first time, directly addresses complex indel detection that has been barely touched in the cancer field. More importantly, our analysis discovered 285 complex indels in cancer genes such as PIK3R1, GATA3, and TP53, revealing an unexpected high prevalence of these events in human cancers. (more…)
Author Interviews, Breast Cancer, Cancer Research, Depression / 17.12.2015

MedicalResearch.com Interview with: Ruhi Kanani  Cancer Epidemiology and Population Health Research Oncology King's College London London, UK  MedicalResearch.com: What is the background of this study? What are the main findings? Response: There is a long history of research investigating the possible association between psychological and physical health. This study is the first to analyse cancer registration information and hospital records of depression for a large group of women with breast cancer in South East England. 77, 173 women diagnosed with breast cancer between 2000 and 2009 were included and followed until the end of 2010. 955 women had a record of depression, 422 before, and 533 in the year after their cancer diagnosis. The results showed that women with a record of depression had a worse overall survival. This was particularly so for those with a  new record of depression after the cancer diagnosis, who had a 45% higher risk of death from all causes compared to those who didn’t develop depression after their cancer diagnosis. (more…)
Author Interviews, Cancer Research / 14.12.2015

MedicalResearch.com Interview with: Lindsey Torre, MSPH  Epidemiologist, Surveillance Research Surveillance Research group at the American Cancer Society Medical Research: What is the background for this study? What are the main findings? Response: This study updates a previous study published in 2010 using the latest available data on cancer incidence and mortality from cancer and vital registration around the world. We found that while high-income countries still have the highest cancer rates in the world, some low- and middle-income countries now also have elevated cancer rates. Also, mortality rates for common cancers such as lung, breast, and colorectum are declining in high-income countries, while they are increasing in low-income countries. At the same time, low-income countries still have a disproportionate burden of infection-related cancers, such as stomach, liver, and cervix. (more…)
Author Interviews, Cancer Research, Depression, MD Anderson, Tobacco / 11.12.2015

MedicalResearch.com Interview with: Dr. Eileen H. Shinn PhD Assistant Professor, Department of Behavioral Science Cancer Prevention and Population Sciences MD Anderson Cancer Center The University of Texas Houston, TX  Medical Research: What is the background for this study? What are the main findings? Dr. Shinn: Recent studies with leukemia, breast, lung, renal and liver cancer patients have shown that patients with depression have worsened survival.  These effect sizes are small, but independent of any of the traditional factors that are known to impact survival, such as extent of cancer, types of treatment administered and baseline health and age of the patient.  The current thinking is that cancer patients who are depressed have chronically heightened responses to stress; the constant release of stress hormones trigger changes in the tumor itself (such as noradrenergically-driven tumor angiogenesis) or may weakens the body’s immune function and ability to resist tumor growth. When we measured depression in newly diagnosed patients with oropharyngeal cancer (cancer of the base of tongue and tonsil), we found that those patients who scored as depressed were 3.5 times more likely to have died within the five year period after their diagnosis, compared to nondepressed patients.  We also found that patients who were depressed were also 3.8 times more likely to have their cancer recur within the first five years after diagnosis.  We also found that patients who continued to smoke after diagnosis were more likely to recur within the first five years. These effect sizes were larger than those typically found in recent studies.  We believe that the larger effect size may be due to the tight eligibility criteria ( e.g., we did not include patients who already had recurrent disease, we only included patients with one specific type of head and neck cancer, oropharyngeal) and also due to controlling other known factors (all patients completed individualized treatment regimens of radiation/ chemoradiation at a comprehensive cancer center and patients with more advanced disease stage were more likely to have received treatment intensification compared to patients with early stage disease).  In all, we had 130 patients, one of the largest prospective studies with oropharyngeal cancer to examine the effect of depression on cancer outcome. (more…)
Author Interviews, Cancer Research, Chemotherapy, Dermatology, JAMA / 11.12.2015

MedicalResearch.com Interview with: Chia-Yu Chu, MD, PhD Associate Professor, Department of Dermatology National Taiwan University Hospital Medical Research: What is the background for this study? What are the main findings? Dr. Chia-Yu Chu: It has been well known that EGFR TKIs could cause skin toxicities (acneiform eruptions, pruritus, xerosis and paronychia). However, incidences of these skin toxicities have varied according to the different clinical trials, some of which even simply use “skin rash” instead of specific cutaneous findings in the reports. Afatinib, in contrast to first generation EGFR TKIs like gefitinib and erlotinib, is a second generation EGFR TKI with irreversible inhibition to not only EGFR, but also HER2 and ErbB4. Whether afatinib cause more skin toxicities remained unknown. Many of our patients received 2 or even 3 different EGFR TKIs with adequate drug exposure and washout period. Therefore, we had an opportunity to compare skin toxicities in “same patients” receiving different EGFR TKIs, and we found that around 30% of patients receiving afatinib developed paronychia whereas only 10% in gefetinib or erlotinib. This was the only significant difference between the 3 drugs. We also found afatinib treated patients needed significantly more dermatologic visits within 180 days of treatments and the reason was due to higher incidence of afatinib-related paronychia. Interestingly, regardless of causative agents, once skin toxicities developed they could be managed effectively in the same manners. (more…)
Author Interviews, Cancer Research, Cleveland Clinic, Heart Disease / 05.12.2015

MedicalResearch.com Interview with: Sadeer G Al-Kindi, MD Fellow, Harrington Heart and Vascular Institute Onco-Cardiology Program, Advanced Heart Failure and Transplant Center, Harrington Heart and Vascular Institute, University Hospitals Case Medical Center Cleveland, OH Medical Research: What is the background for this study? Dr. Al-Kindi: Cardiovascular disease and cancer are the most common causes of death in the United States. They often have the same risk factors (for example, smoking, advancing age, obesity). Many cancers are treated with drugs that can have detrimental effect on the heart thus limiting their use. Some studies have suggested that cardiovascular diseases can worsen outcomes in patients with cancer. The emergence of onco-cardiology programs led to multidisciplinary care of patients with cancer and heart disease. Given this tight relationship between cancers and cardiovascular disease, we hypothesized that heart disease and its risk factors are very common in patients diagnosed with cancer. Medical Research: What are the main findings? Dr. Al-Kindi: Using a very large clinical database of 1/8th of the US population, we identified patients with most common cancers that are treated with cardiotoxic medications and identified the prevalence of cardiovascular diseases. Overall, prevalence was 33% for hematologic malignancies (leukemia and lymphoma), 43% for lung cancers, 17% for breast cancers, 26% for colon cancers, 35% for renal cancers, and 26% for head and neck cancers. Peripheral artery disease, coronary artery disease and cerebrovascular diseases were the most common, followed by heart failure, and carotid artery disease. Despite the high prevalence, only about a half of these patients were on the cardiovascular medicines and half were referred to cardiologists. (more…)