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Author Interviews, Brigham & Women's - Harvard, Colon Cancer, Exercise - Fitness, JAMA / 26.05.2016

MedicalResearch.com Interview with: NaNa Keum, ScD| Harvard T. H. Chan School of Public Health Department of Nutrition Departments of Nutrition and Epidemiology, Harvard T.H. Chan School of Public Health Boston, MA 02115 MedicalResearch.com: What is the background for this study? Response: While general health benefits of physical activity are well-known, evidence on its specific benefits on cancer endpoints is limited and physical activity guidelines for cancer prevention lack details in terms of the optimal dose, type and intensity of physical activity. MedicalResearch.com: What are the main findings? Response: We found that the optimal exercise regime to prevent overall digestive system cancers may be to accumulate 30 MET-hours/week of physical activity primarily through aerobic exercise and regardless of its intensity. (more…)
Author Interviews, Cancer Research, Heart Disease, JAMA / 26.05.2016

MedicalResearch.com Interview with: David Conen MD MPH Department of Medicine University Hospital Basel Basel Switzerland MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Conen: A previous study of a contemporary population with atrial fibrillation (AF) treated with oral anticoagulation showed that over a third of all deaths were due to non-cardiovascular causes, and malignancies accounted for the largest proportion of these deaths. These data suggested that AF patients may have an increased risk of malignancies, but little data existed to support this hypothesis. During more than 19 years of follow-up, our study showed that atrial fibrillation was a significant risk factor for the occurrence of malignant cancer. After taking into account a large number of other risk factors and co-morbidities, the risk of cancer was approximately 50% higher among women with new-onset AF compared to women without AF. The risk of cancer was highest in the first 3 months after new-onset AF but remained significant beyond 1 year after new-onset AF (adjusted HR 1.42, p<0.001). We also observed a trend towards an increased risk of cancer mortality among women with new-onset AF. (more…)
Author Interviews, Exercise - Fitness, JAMA, Lifestyle & Health / 23.05.2016

MedicalResearch.com Interview with: Steven C. Moore PhD, MPH Division of Cancer Epidemiology and Genetics Rockville, MD  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Moore: More than half of Americans fail to meet recommended levels of regular physical activity; physical inactivity has become a major public health concern. Physical activity during leisure time is known to reduce risks of heart-disease and all-cause mortality, as well as risks of colon, breast, and endometrial cancers. However, less is known about whether physical activity reduces risk of other cancers. Hundreds of prospective studies have examined associations between physical activity and risk of different cancers. Due to small case numbers, results have been inconclusive for most cancer types. In this study, we examined how leisure-time physical activity relates to risk of 26 different cancer types in a pooled analysis of 12 prospective cohort studies with 1.44 million participants. Our objectives were to identify cancers associated with leisure-time physical activity, and determine whether associations varied by body size and/or smoking history. (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, JAMA, Lifestyle & Health / 23.05.2016

MedicalResearch.com Interview with: Mingyang Song
Research Fellow
Department of Nutrition
Harvard T.H. Chan School of Public Health  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Although substantial data support the importance of lifestyle factors for cancer risk, a study published in Science early last year “led some to conclude that only a third of the variation in cancer risk among tissues is attributable to environmental factors or inherited predispositions, while most is due to random mutations arising during stem cell divisions, so-called bad luck.” That study “has been widely covered by the press and has created confusion for the public regarding the preventability of cancer.” In response to that study, we conducted this study to estimate how many cancer cases and deaths in the US can be potentially attributed to common lifestyle factors. Our study showed that about 20-30% of cancer incidences and 40-50% of cancer deaths may be avoided if everyone in the US adopted a lifestyle pattern that is characterized by “never or past smoking (pack-years <5), no or moderate alcohol drinking ([1]1 drink/d for women,[1]2 drinks/d for men), BMI of at least 18.5 but lower than 27.5, and weekly aerobic physical activity of at least 75 vigorous-intensity or 150 moderate-intensity minutes”. (more…)
Author Interviews, Cancer Research, Colon Cancer, Genetic Research / 14.05.2016

MedicalResearch.com Interview with: Dr. Geoffrey Liu, MD MSC Princess Margaret Hospital/Ontario Cancer Institute University of Toronto Toronto, Ontario Canada MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Liu: Cetuximab is a monoclonal antibody therapy used in metastatic colorectal cancer patients when other chemotherapy options have been exhausted. Currently, the only useful biomarker to determine whether metastatic colorectal cancer patients will benefit from the drug, cetuximab, is whether patients carry a RAS mutation in their tumours. We evaluated additional biomarkers using samples from a Phase III clinical trial led by the Canadian Cancer Trials Group and the Australasian Gastrointestinal Trials Group. Our study identified a germline, heritable biomarker, a FCGR2A polymorphism, that further identifies an additional subgroup of patients who would benefit most from receiving cetuximab. This is important because the drug does have toxicity and is expensive to use; patients who are found not to likely benefit from this drug can go on quickly to try other agents, including participation in clinical trials. (more…)
Author Interviews, Cancer Research, JNCI, Toxin Research / 14.05.2016

MedicalResearch.com Interview with: Dr. Debra Silverman Sc.D Branch Chief and Senior Investigator in the Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology & Genetics National Cancer Institute MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Silverman: We know that bladder cancer mortality rates have been elevated in northern New England for at least five decades. Incidence patterns in Maine, New Hampshire and Vermont are similar—about 20% higher than those for the United States overall. Elevated rates have been observed in both men and women, suggesting the role of a shared environmental etiologic factor. A unique feature of northern New England is that a high proportion of the population uses private wells as their primary source of drinking water. The well water may contain low-to-moderate levels of arsenic. There are two possible sources of this arsenic contamination:
  • Naturally occurring arsenic from geological sources (released from rock deep in the earth)
  • Leaching of arsenic-based pesticides used on food crops many years ago. From the 1920s through the 1960s there was extensive agricultural use of arsenic-based pesticides. These compounds were used on food crops such as blueberries, apples and potatoes. Residue from the treatments may have leached into the ground water.
Intake of water containing high levels of arsenic is an established cause of bladder cancer, largely based on studies conducted in highly exposed populations. However, emerging evidence suggests that low-to-moderate levels of exposure may also increase bladder cancer risk. To explore possible reasons for the excess incidence of bladder cancer in northern New England, we conducted a large, comprehensive population-based case-control study in Maine, New Hampshire and Vermont. We examined the role of known and suspected bladder cancer risk factors, with a focus on private well water consumption and arsenic levels in drinking water. The major cause of bladder cancer is cigarette smoking. Some occupational exposures (e.g., exposure to metalworking fluids such as that experienced by metalworkers and some types of machine operators) are also associated with elevated risk. However, smoking and occupational exposures do not appear to explain the New England bladder cancer excess. This study was funded and carried out by researchers in the NCI Division of Cancer Epidemiology and Genetics in collaboration with the Geisel School of Medicine at Dartmouth, the Departments of Health for Maine, New Hampshire, and Vermont, and the US Geological Survey. We reported that heavy consumption of drinking water from private dug wells (which are shallow—less than 50 feet deep—and susceptible to contamination from manmade sources than drilled wells), established prior to 1960 (when arsenic-based pesticides were widely used), may have contributed to the longstanding bladder cancer excess in northern New England. We saw that cumulative arsenic exposure from all water sources showed an increasing risk with increasing exposure (exposure-response relationship). Among the highest exposed participants, risk was twice that of the lowest exposure group. (Cumulative arsenic exposure is a measure of the average daily arsenic intake by number of days of arsenic exposure.) (more…)
Author Interviews, Cancer Research, Colon Cancer, Immunotherapy, Leukemia, Multiple Sclerosis, Neurology / 13.05.2016

MedicalResearch.com Interview with: PD Dr. Mathias Buttmann Senior Consultant Neurologist and Head of the Multiple Sclerosis Outpatient Clinic University of Wuerzburg Wuerzburg, Germany  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Buttmann: The synthetic anthracenedione mitoxantrone is approved for disease-modifying treatment of patients with aggressive forms of relapsing or secondary progressive multiple sclerosis (MS). It has been known for years that this DNA-intercalating agent increases the risk of acute myeloid leukemia. We performed a retrospective cohort study to investigate whether mitoxantrone also increases the risk for other types of malignancies. We included all 677 mitoxantrone-treated  multiple sclerosis patients who were seen at our large German academic MS centre between 1994 and 2007 and collected follow-up information on the occurrence of malignancies, death and causes of death as of 2011. Follow-up was complete in 676 patients. The median age at mitoxantrone initiation was 41 years and the median follow-up duration was 8.7 years. We identified 37 patients with a malignancy after mitoxantrone initiation, among them 4 cases of acute myeloic leukemia and 7 cases of colorectal cancer. Compared to the general population matched for sex, age and year of occurrence, we calculated an 1.5-fold increased incidence of any type of malignancy, a tenfold increased incidence of acute myeloic leukemia and a threefold increased incidence of colorectal cancer, while the incidence of other types of malignancies was not increased. Higher age at mitoxantrone initiation but neither higher cumulative mitoxantrone dose nor treatment with other immuosuppressive agents was identified as a malignancy risk factor. Fifty-five patients had died, among them 12 from a malignancy. Our study confirmed previous reports on an increased incidence of acute myeloic leukemia after mitoxantrone treatment and newly described an association between mitoxantrone therapy and an increased incidence of colorectal cancer. (more…)
Author Interviews, Biomarkers, Cancer Research, Genetic Research, MD Anderson / 11.05.2016

MedicalResearch.com Interview with: Dr. Han Liang PhD Associate Professor and Deputy Department Chair, Department of Bioinformatics and Computational Biology The University of Texas MD Anderson Cancer Center Faculty Member, Baylor College of Medicine Houston, TX MedicalResearch: What is the background for this study? What are the main findings? Dr. Liang: An individual’s sex has been long recognized as a key factor affecting the risk of cancer development and management. However, previous studies on the sex effect have been limited to individual genes, single molecular data types, and single cancer lineages. We performed a comprehensive analysis of molecular differences between male and female patients in a diversity of cancer types and revealed two sex-effect groups. One group contains a small number of sex-affected genes, whereas the other shows much more extensive sex-biased molecular signatures. More than half of clinically actionable genes (e.g., therapeutic targets or biomarkers) show sex-biased signatures. (more…)
Aging, Author Interviews, Cancer, Cancer Research / 10.05.2016

MedicalResearch.com Interview with: Corinne Leach, MPH, MS, PHD Strategic Director, Cancer and Aging Research American Cancer Society, Inc. Atlanta, GA 30303 MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Leach: Using linked data from cancer registries and the Medicare Health Outcomes Survey, we prospectively examined the short-term impact of cancer on the functioning, development of and worsening of age-related health conditions among 921 older adults who developed cancer compared to 4,605 propensity score matched controls. We found that cancer groups demonstrated greater declines in activities of daily living and physical functioning compared to controls with the greatest change for lung cancer patients. Having a cancer diagnosis increased risk for depression but did not increase the odds of developing arthritis in the hand/hip, incontinence (except for prostate cancer), or vision/hearing problems. Having a cancer diagnosis also did not exacerbate the severity of arthritis or foot neuropathy. (more…)
Author Interviews, Colon Cancer, Menopause, Surgical Research / 05.05.2016

MedicalResearch.com Interview with: Josefin Segelman MD, PhD Senior consultant colorectal surgeon Department of Molecular Medicine and Surgery Karolinska Institutet Ersta Hospital Stockholm Sweden MedicalResearch.com: What is the background for this study? Dr. Segelman: Hormonal factors influence the development of colorectal cancer. Observational studies and clinical trials have reported a protective effect of hormone replacement therapy and oral contraceptives. Oophorectomy alters endogenous levels of sex hormones, but the effect on colorectal cancer risk is unclear. Removal of the ovaries alters levels of sex hormones in both pre- and postmenopausal women. In premenopausal women, bilateral oophorectomy is followed by surgical menopause as the endogenous estrogen levels drop. Both before and after natural menopause, bilateral oophorectomy promptly decreases endogenous androgen levels by half as the ovaries and adrenals are equally important for androgen production. MedicalResearch.com:  What are the main findings? Dr. Segelman: The present nationwide cohort study explored the association between removal of the ovaries for benign indications and subsequent risk of colorectal cancer. Among 195 973 women who underwent the procedure from 1965 – 2011, there was a 30% increased risk of colorectal cancer compared with the general population. After adjustment for various factors, women who underwent bilateral oophorectomy had a higher risk of rectal cancer than those who had unilateral oophorectomy (HR 2.28, 95% CI 1.33-3.91). (more…)
AACR, Author Interviews, Cancer Research, Lung Cancer, Race/Ethnic Diversity, Surgical Research / 02.05.2016

MedicalResearch.com Interview with: Asal Mohamadi Johnson, PhD, MPH Assistant Professor of Epidemiology, Integrative Health Science Stetson University DeLand, FL 32723 MedicalResearch.com: What is the background for this study? Dr. Johnson: Public health research is primarily focused on neighborhood poverty and racial disparities by illustrating differences between white and black individuals or communities. For example, it has been established that African Americans have higher cancer mortality rates and are less likely to receive appropriate treatment that whites. What we wanted to know in this study was the impact of living in segregated areas apart from other area level characteristics such as poverty or education. Instead of solely looking at health disparities between whites and black patients, our study focused on differences in survival among black patients with early stage Non-Small Cell Lung Cancer (NSCLC) living in different levels of neighborhood segregation. (more…)
AACR, Author Interviews, Biomarkers, Cancer Research, Personalized Medicine, Stanford / 01.05.2016

MedicalResearch.com Interview with: Dr. Elodie Sollier Chief Scientific Officer at Vortex Biosciences MedicalResearch.com: What is the background for this study? What are the main findings? Response: Circulating Tumor Cell (CTC) burden may be a useful biomarker of response to targeted therapy in PDX (Patient Derived Xenograft) mouse models. Vortex Biosciences’ technology has been proven to enrich CTCs from human blood, but use of the technology with mouse blood had not yet been explored. In this poster, human CTCs are isolated with both high efficiency and purity from xenograft model of breast cancer using Vortex’s technology. Circulating Tumor Cell enumeration increased as the tumor burden increased in the mouse demonstrating its utility as a biomarker for drug treatment response. (more…)
Author Interviews, Cancer Research, Cost of Health Care / 28.04.2016

MedicalResearch.com Interview with: Stacie B. Dusetzina, PhD Assistant Professor Division of Pharmaceutical Outcomes and Policy Eshelman School of Pharmacy University of North Carolina at Chapel Hill Chapel Hill, NC  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Dusetzina: Drug prices are of significant policy interest, particularly the prices for so-called “specialty” medications which are used to treat rare and/or complex conditions like cancer. In this study I estimated monthly price for orally-administered cancer treatments that were approved between 2000 and 2014. First I looked at the price of the drug during the year of initial FDA approval and then I looked at annual changes in the price after the year of approval. The main findings are that, even after inflation adjustment, the monthly price paid for orally-administered cancer treatments is increasing rapidly both at the time of approval and in subsequent years. As an example, if you compare average monthly prices during the first year post-approval for treatments approved between 2000-2010 to those approved after 2010 there was a major increase in launch prices from $5,529 per month to $9,013 per month. Year-to-year changes in price after launch varied a lot by drug ranging from decreases in price of -2.7% per year to increases of 11.4% per year. However, nearly all of the products studied increased in price over time. (more…)
Author Interviews, Cancer Research, JAMA, Karolinski Institute, Mental Health Research / 28.04.2016

MedicalResearch.com Interview with: Donghao Lu MD, PhD candidate Department of Medical Epidemiology & Biostatistics, Karolinska Institutet Stockholm MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Lu: Psychiatric comorbidities are common among cancer patients. However, whether or not there is already increased risk of psychiatric disorders during the diagnostic workup leading to a cancer diagnosis was largely unknown. We found that, among cancer patients, the risks for several common and potentially stress-related mental disorders, including depression, anxiety, substance abuse, somatoform/conversion disorder and stress reaction/adjustment disorder started to increase from ten months before cancer diagnosis, peaked during the first week after diagnosis, compared to cancer-free individuals in Sweden. (more…)
Author Interviews, Cancer Research / 27.04.2016

MedicalResearch.com Interview with: E. Premkumar Reddy, Ph.D. Professor, Department of Oncological Sciences and Department of Structural and Chemical Biology Director, Experimental Cancer Therapeutics Mount Sinai School of Medicine New York, NY 10029  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Reddy: It is now well established that  cancer cells harbor mutations in their genome which are responsible for uncontrolled proliferation.  Nearly 30 years ago, we as well as two other groups discovered that RAS genes are often mutated in human cancers.  Later studies showed that nearly 25-30% of human cancers contain this mutation and these mutations can be caused by chemical carcinogens such as tobacco smoke.  Since then there has been an intense effort to understand the biological functions of RAS and to develop drugs that block the activity of these mutant RAS genes.  Although molecular oncologists have made significant headway in understanding these mutations and their impact on cellular signaling, little progress has been made towards developing drugs that systematically target the RAS oncogenes.  This lack of progress has led many in the field to label RAS as “undruggable”.  However, basic research conducted by scientists in this field has revealed that RAS proteins function as ON-OFF switches to signal cells to grow or not to grow because of their ability to bind to a large number of cellular proteins and transmit this signal to their binding partners.  These findings also revealed that mutations in RAS genes leaves them in a permanent “ON” position which continues to transmit growth signals permanently.  Since most efforts to develop drugs that bind to RAS proteins and reverse their activity failed, we took a different approach to block these signals.  Since transmission of growth signals by RAS genes requires their interaction with cellular proteins, all of which contain a domain called “RAS-Binding Domain (RBD)” we created a drug named “Rigosertib” that binds to these RBDs and block their binding to RAS, thereby interrupting RAS signals.  When Rigosertib was tested in animals, it could readily inhibit the growth of human tumors that contain RAS mutations.  Our studies also show that Rigosertib is a very safe drug with minimal side-effects. (more…)
AACR, Author Interviews, Biomarkers, Cancer Research, Colon Cancer, Technology / 27.04.2016

MedicalResearch.com Interview with: Dr. Elodie Sollier PhD Chief Scientific Officer at Vortex Biosciences MedicalResearch.com: What is the background for this study? What are the main findings? Response: Vortex Biosciences has developed a fast and simple way to isolate and collect intact circulating tumor cells (CTCs) directly from whole blood in less than an hour using a process based on microfluidics. To better understand the utility of the technology for the clinical setting, PCR-based Sanger sequencing was used to profile the mutations of CTCs isolated from blood from metastatic Colorectal cancer patients. The mutations were compared to primary tumor biopsies, secondary tumor biopsies and ctDNA. There are 3 primary take-aways:
  1. The Vortex technology captures CTCs with enough purity to perform sensitive and accurate PCR-based Sanger sequencing.
  2. Mutations present in primary and secondary tumors can be identified in both CTCs and ctDNA making liquid biopsies a valuable alternative to tissue biopsies.
  3. While there is general consistency of mutations identified, some mutations are only identified in CTCs while others only in ctDNA demonstrating how these are indeed complimentary.
(more…)
Author Interviews, Cancer Research, Cost of Health Care, Radiology / 20.04.2016

MedicalResearch.com Interview with: Dr. Christine Fisher MD, MPH Department of Radiation Oncology University of Denver MedicalResearch.com: What is the background for this study? Dr. Fisher: Screenable cancers are treated by oncologists every day, including many in invasive, advanced, or metastatic settings.  We aimed to determine how health insurance status might play into this, with the hypothesis that better access to health care would lead to presentation of earlier cancers.  While this sounds intuitive, there is much debate over recent expansions in coverage through the Affordable Care Act and how this may impact health in our country. MedicalResearch.com: What are the main findings? Dr. Fisher: The findings confirm that those without health insurance present with more advanced disease in breast, cervix, colorectal, and prostate cancers, including tumor stage, grade and elevated tumor markers.  That is to say, all else being equal for risk of cancer, lack of health insurance was an independent risk factor for advanced presentation.  (more…)
Author Interviews, Cancer Research, PLoS, Vitamin D / 15.04.2016

MedicalResearch.com Interview with: Sharon L. McDonnell MPH GrassrootsHealth Encinitas, California Medical Research: What is the background for this study? What are the main findings? Response: Higher vitamin D levels in the blood have been associated with a lower risk of multiple cancer types including colorectal and breast. Using data from two study cohorts of women aged 55 years and older (N=2,304), we investigated the association between serum 25(OH)D concentration, the marker of vitamin D in the blood, and risk of all non-skin cancers combined across a broad range of 25(OH)D concentrations. We found that women with 25(OH)D concentrations ≥40 ng/ml had a 67% lower risk of cancer compared to women with concentrations <20 ng/ml. We also found that the greatest decrease in risk occurred between ~10-40 ng/ml. These findings suggest that increasing 25(OH)D concentrations to a minimum of 40 ng/ml could substantially reduce  cancer incidence and associated mortality in the population. (more…)
Author Interviews, BMJ, Cancer Research, Education / 08.04.2016

MedicalResearch.com Interview with: Dr Alex Ghanouni Research Associate UCL Research Department of Epidemiology and Public Health Health Behaviour Research Centre London MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Ghanouni: This study comes out of growing concern among academics, doctors, and policymakers about the unintended harms of healthcare interventions. One prominent issue in the ongoing debate is ‘overdiagnosis’, that is detection of disease that would not have caused symptoms or death if it had remained undetected. There are many contexts in which overdiagnosis can occur but one of the most prominent is cancer screening, in which asymptomatic individuals undergoing testing may have slow-growing cancers detected that would never have otherwise come to light. However, because it is impossible to be sure which cancers are slow-growing and which are aggressive, most are treated. This means that overdiagnosis can lead to harm through the anxiety caused by a disease label and the negative effects of treatment (e.g. surgery) that is actually unnecessary. Despite professional concern about overdiagnosis, previous research has found that the public is mostly unaware that it exists. One study that was particularly relevant to our research was an Australian survey in which members of the public were asked whether they had encountered the term before and what they thought it meant. Although around half the sample stated that they had heard or seen the term before, only 41% were able to provide a definition that was approximately correct. We tested the extent to which this was true as part of an online survey of adults aged 50-70 years in the UK. We found that recognition of the term was very low (only 30%) and almost no-one (3%) gave an answer that was strictly accurate. Responses often indicated misconceptions (e.g. “misdiagnosis”, “false positive diagnosis”, or being “overly health conscious”). (more…)
Author Interviews, Cancer, Cancer Research, End of Life Care / 06.04.2016

MedicalResearch.com Interview with: Holly G. Prigerson, Ph.D. Irving Sherwood Wright Professor in Geriatrics Professor of Sociology in Medicine Director, Center for Research on End of Life Care Weill Cornell Medicine New York Presbyterian Hospital New York City, New York 10065  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Prigerson: Patients need to know their prognosis to be informed consumers of end-stage cancer care. We found that most patients have an overly optimistic view of their life-expectancy and that few patients base their life expectancy estimate on communications with their healthcare providers. It was striking that 0% of black patients said their prognostic estimate was based on a medical professional. (more…)
Author Interviews, Cancer Research, Technology, UCLA / 26.03.2016

MedicalResearch.com Interview with: Dr. David Wong D.M.D, D.M.S.C Professor Associate Dean for Research Director for UCLA Center for Oral/Head & Neck Oncology Research (COOR) Felix and Mildred Yip Endowed Chair in Dentistry UCLA MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Wong: The EFIRM technology is an electrochemical technology developed for the optimal detection of saliva targets for molecular diagnostics. It is a multiplexible platform (nucleic acid and proteins) that has sensitivity and specificity that comparable with PCR and luminex-based assays. It permits direct target detection in bio-samples without processing. (more…)
Author Interviews, Cancer Research, JAMA, Pediatrics / 25.03.2016

MedicalResearch.com Interview with: Lee J. Helman, MD Senior Investigator Pediatric Oncology Branch Head, Molecular Oncology Section Acting Director, Center for Cancer Research and CCR Scientific Director for Clinical Research National Cancer Institute Bethesda, Maryland MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Helman: It was known that most gastrointestinal stromal tumors (GISTS) that occur in children and young adults do not contain cKIT or PDGFRA mutations that drive more than 90% of adult GIST tumors.  Since GISTs are quite rare in the pediatric and young adult population, we decided to establish a clinic at NIH that would allow us to study the most patients to try to define these tumors both clinically and molecularly. We were able to bring both patients and physicians interested in pediatric GIST from around the country to the NIH to begin to collect and study these patients. Of the 95 patients in this cohort study that lacked cKIT or PDGFRAmutations, 84 were found to have succinate dehydrogenase (SDH) deficient (SDH-deficient) GIST (75% due to SDH A, B, C, or D mutations, and 25% due to SDHC promoter hypermethylation. Since these tumors are driven by SDH loss and not due to KIT or PDGFR mutations, they do not generally respond to standard treatments for GIST that target these kinases. The mechanism of SDH-deficiency is important, since SDH mutations are commonly germ line and therefore require genetic counseling and family testing, while the SDHC promoter methylation is not a germ line alteration and therefore does not require genetic counseling.  Finally, any patient with SDH-deficient GIST is also at risk for development of paraganglioma and should be screened on a regular basis for these tumors.  (more…)
Author Interviews, Cancer Research, Imperial College / 21.03.2016

MedicalResearch.com Interview with: Dr Olivier E Pardo PhD Team Leader Imperial College Division of Cancer Hammersmith Hospital London UK  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Pardo: Metastatic dissemination, the ability of tumour cells to go and colonise organs distant from the primary disease site, is the principal cause for failing to cure patients with cancer. This is particularly true in the case of breast cancer where resection of local disease offers good chances of cure but metastatic dissemination that may appear at a later stage carries very poor prognosis. Surgical resection is also the only true curative strategy for localised lung cancer. Hence, a better understanding of the mechanisms controlling the dissemination of tumour cells is likely to propose novel targets for combination therapy that will improve the survival of cancer patients. Here, we showed that an enzyme, named MARK4, controls the ability of lung and breast cancer cells to move and invade. When we lower MARK4 levels, it prevents cancer cells from moving by changing their internal architecture, making them unfit to invade. Consequently, these cells were unable to efficiently form metastasis in mouse cancer models. Confirming the role of this enzyme in cancer, we show that breast and lung cancer patients with increased levels of MARK4 in their tumours have poorer prognosis. We found that what controls the levels of MARK4 in cells is miR-515-5p, a small oligonucleotide sequence called a microRNA. When present in the cells, miR-515-5p prevents the expression of MARK4. Incidentally, the loss of miR-515-5p correlates with increased metastasis and poorer prognosis in mouse cancer models and patients, respectively. (more…)
Author Interviews, Cancer Research / 19.03.2016

MedicalResearch.com Interview with: Douglas.A. Lauffenburger PhD Ford Professor of Biological Engineering, Chemical Engineering, and Biology Head, Department of Biological Engineering Massachusetts Institute of Technology Cambridge, MA 02139  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Lauffenburger: We aimed to advance understanding concerning causes of tumor resistance to kinase inhibitor drugs, which limits effectiveness for many therapeutics even when indicated by specific genetic mutations in the new ‘personalized medicine’ paradigm.  We discovered a new mechanism underlying this resistance at least for a number of otherwise promising drugs currently in clinical use as well as further clinical trials.  Our discovery was based on realizing that the same oncogenic signaling driving tumor cell proliferation and invasiveness at the same time activates proteolytic shedding of receptor tyrosine kinases not involved in the targeted oncogenic pathway, shutting down additional signaling inputs.  Thus, when the targeted pathway is inhibited by the intended drug, this shedding is concomitantly diminished — now permitting “bypass" pathways to be activated downstream of these alternative receptor inputs.  Moreover, we showed that measurement of a set of key shed receptors (primarily AXL and MET, in our examined case of MEK pathway inhibitors for melanoma and triple-negative breast tumors) in patient blood serum samples could predict effectiveness of these inhibitors: when the shed levels were high, the drugs were less effective because of the correspondingly great potential for bypass signaling upon drug treatment.  In follow-up mouse experiments, we demonstrated increased effectiveness of a MEK inhibitor when combined with either an AXL inhibitor or a proteolysis inhibitor, thereby confirming the mechanism and proving an avenue for overcoming it. (more…)
Author Interviews, Cancer, Cancer Research, Cost of Health Care / 14.03.2016

MedicalResearch.com Interview with: Hrishikesh Kale School of Pharmacy Virginia Commonwealth University MedicalResearch.com: What is the background for this study? What are the main findings? Response: The cost of cancer care in the United States is extremely high and escalating every year. Because of increased cost sharing, patients are paying higher out-of-pocket costs for their treatments. Along with high medical expenses, cancer survivors face problems such as loss of employment and reduced productivity. It has been well-established in the literature that because of high out-of-pocket costs, many cancer survivors forgo or delay medical care and mental health-related services and avoid filling prescriptions. This puts their physical and mental health at risk. A related issue is the growing number of cancer survivors in the U.S. As of January 2014, there were approximately 14.5 million cancer survivors in the U.S. By 2024, this number is expected to reach 19 million as a result of improved survival among patients with cancer along with an aging population. Therefore, we decided to investigate the prevalence and sources of financial problems reported by a nationally representative sample of cancer survivors from the 2011 Medical Expenditure Panel Survey. We also studied the impact of cancer-related financial burden on survivors’ health-related quality of life and psychological health. (more…)
Author Interviews, Cancer Research, JAMA / 11.03.2016

MedicalResearch.com Interview with: Joseph Unger, PhD, MS SWOG Statistical Center Assistant Member, Public Health Sciences Division, Fred Hutchinson Cancer Research Center Affiliate Assistant Professor, Health Services Research, University of Washington Seattle, WA  98109-1024 MedicalResearch.com: What is the background for this study? Dr. Unger: The rate at which trials are positive has previously been examined, and the relationship between trial results and publication rates in the context of publication bias has also been studied. But the comparative scientific impact of positive vs negative clinical trials using citation data has not been investigated We used the phase III trial database of SWOG, a major national cooperative clinical trials group, in combination with its trial publication database and citation data from Google Scholar, to compare the scientific impact of positive vs negative phase III cancer clinical treatment trials. (more…)
Author Interviews, BMJ, Cancer Research, Colon Cancer, Psychological Science / 09.03.2016

MedicalResearch.com Interview with: Benedicte Kirkøen, PhD candidate Bowel Cancer Screening in Norway – a pilot study Cancer Registry of Norway (Kreftregisteret) MedicalResearch.com: What is the background for this study? Response: Randomised controlled trials have demonstrated that screening for colorectal cancer (CRC) can reduce CRC related mortality, but the total benefit and harm of national cancer screening programmes are under debate. Saving relatively few lives requires a large number of people to be screened. Most people who attend screening will never develop cancer, but may be exposed to potential psychological stress by participation. Cancer is one of the largest threats to peoples’ health, and participating in screening for cancer might therefore cause anxiety. In Norway, colorectal cancer incidence has nearly tripled since the 1950s, and currently a large randomised pilot study of a national screening programme (Bowel Cancer Screening in Norway) is investigating the effect of screening on reduction in CRC incidence and mortality. As part of an evaluation of the benefits and harms of the pilot, we investigated the psychological effect of screening participation in a large group of participants. Of particular interest to us were participants who received a positive screening result and were referred to colonoscopy. (more…)
Author Interviews, Chemotherapy, Pancreatic, Vanderbilt / 07.03.2016

MedicalResearch.com Interview with: Alexander A. Parikh, M.D., M.P.H. Associate Professor of Surgery Director of Hepatobiliary, Pancreatic and GI Surgical Oncology Director, Vanderbilt Pancreas Center Vanderbilt University Medical Center Nashville, TN MedicalResearch.com: What is the background for this study? Dr. Parikh: Although adjuvant chemotherapy has been proven to increase survival after successful resection of pancreatic cancer and has become the standard of care worldwide, the use of adjuvant chemoradiation is more controversial. The vast majority of randomized trials have failed to show a significant improvement in survival with the use of chemoradiation after pancreatic cancer resection. Furthermore, our own report from the multi-institutional Central Pancreatic Consortium (CPC) published several years ago failed to show a benefit in the use of chemoradiation except in high-risk groups such as lymph node positive disease. The purpose of the current study was to investigate the patterns of recurrence with the use of adjuvant chemotherapy or chemoradiation in hopes of explaining some of these differences. It was our hypothesis that systemic chemotherapy would prevent distant recurrence (and perhaps local) while chemoradiation would only prevent local recurrence and thereby have less impact on overall survival. MedicalResearch.com: What are the main findings? Dr. Parikh: The main findings demonstrated that adjuvant chemotherapy led to an improvement in both local and distant recurrence with a corresponding improvement in overall survival while chemoradiation only led to an improvement in local recurrence but not distant nor overall survival. (more…)