Author Interviews, Cancer Research, PNAS / 21.01.2016 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…)
Author Interviews, Brigham & Women's - Harvard, Dermatology, JAMA, Melanoma, Transplantation / 20.01.2016

More on Dermatology from Interview with: Pritesh S. Karia, MPH Manager-Dermatologic Oncology Research Program Mohs and Dermatologic Surgery Center Brigham and Women's Hospital Boston, MA 02130  Medical Research: What is the background for this study? Response: Several recent studies have shown a reduced incidence of skin cancer in organ transplant recipients (OTR) treated with sirolimus as first-time therapy and those converted from calcineurin inhibitors to sirolimus. Although cancer formation is one of the main reasons for conversion to sirolimus, studies examining the effect of sirolimus on the risk of subsequent cancer formation in organ transplant recipients who have already been diagnosed with a post-transplant cancer are limited. (more…)
Author Interviews, Dermatology, Melanoma / 20.01.2016

More on Dermatology on Interview with: Myra Sendelweck M.Eng M.D. Candidate 2018 and Robert Dellavalle, MD, PhD, MSPH Chief, Dermatology Service Denver VA Medical Center Denver, CO University of Colorado School of Medicine MedicalResearch: What is the background for this study? What are the main findings? Response: Indoor tanning has increasingly been recognized amongst providers as a public health concern. Recent literature suggests an association between indoor tanning and other risky health behaviors in adolescents. We were intrigued by this association. We analyzed a survey of Colorado high school students and found that those who tanned were also more likely to use various substances, such as steroids, alcohol, marijuana, and illicit drugs. Tanners were over five times as likely to report steroid use! (more…)
ASCO, Author Interviews, Cancer Research, Lymphoma / 18.01.2016

More Cancer Research on 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, Breast Cancer, Genetic Research, NYU / 16.01.2016

More on Breast Cancer Research on Interview with: Dr. Benjamin Neel MD PhD Professor, Department of Medicine Director Perlmutter Cancer Center NYU Langone Medical Center Medical Research: What is the background for this study? What are the main findings? Dr. Neel:  Over the past 10 years, there have been major advances in cancer genomics--i.e., defining what changes in genes are found in different types of cancer cells.  Sometimes, such studies have resulted in the identification of new drug targets, such as EGF receptor mutations or EML-ALK translocations in lung cancer, RAF mutations in melanoma and hairy cell leukemia, and KIT or PDGFR mutations in GIST.  More often, though, either the genetic changes that genomic studies reveal are difficult to target by conventional small molecule drugs or we dont know which of the many mutations found in a given tumor are critical to its proliferation/survival. "Functional genomics" is a parallel approach to tumor genomics, that aims to use large scale screening technology to identify which genes are essential to cancer cell survival/proliferation.  This approach can reveal which genetic changes in cancer cells "drive" the cancer--but it also can find genes on which the cancer becomes dependent because of the other "driver" genes.  One major approach to functional genomics uses short hairpin RNAs (a type of RNAinterference/RNAi) to "knock down" the expression of each gene in a cell.  Scientists can generate a "library" of designer virus particles, each of which expresses a different hairpin that can "knockdown" a different gene.  A large population of tumor cells is then infected with the virus, and scientists use gene sequencing or array based approaches to see which shRNAs become depleted from the starting population of shRNAs; this type of screen is called a "dropout screen". Earlier studies, including by our group, performed dropout screens on smaller numbers of cancer cell lines.  Yet because these screens involved only a few cell lines, they could not represent the large number of sub-types knownt to occur in, for example, breast cancer.  Our study, by using 77 breast cancer lines, has adequate power to survey the landscape of breast cancer. Furthermore, by obtaining parallel genomic information, as well as some information on the breast cancer cell "proteome" (the proteins in these cells), we can couple genomic analysis with functional genomics. In addition, we had drug response information for a large number of these lines, and so were able to make some predictions for drugs that might prove additive for breast cancer therapy. The result is a large number of potential new targets linked to genetic information, as well as new insights into how the different sub-types of breast cancer "rewire" their respective signaling diagrams compared with normal cells. (more…)
Author Interviews, Cancer Research, Technology / 15.01.2016

More on Cancer Research on 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, Brigham & Women's - Harvard, Pancreatic, Pharmacology, PLoS / 15.01.2016

More on Pancreatic Cancer on Interview with: Dai Fukumura, M.D., Ph.D. Joao Incio, M.D. and Rakesh K. Jain, Ph.D Edwin L. Steele Laboratory Department of Radiation Oncology Massachusetts General Hospital Harvard Medical School Medical Research: What is the background for this study? What are the main findings? Dr. Fukumura: This study focused on pancreatic ductal adenocarcinoma, the most common form of pancreatic cancer, which accounts for almost 40,000 cancer death in the U.S. ever year. Half of those diagnosed with this form of pancreatic cancer are overweight or obese, and up to 80 percent have type 2 diabetes or are insulin resistant. Diabetic patients taking metformin – a commonly used generic medication for type 2 diabetes – are known to have a reduced risk of developing pancreatic cancer; and among patients who develop the tumor, those taking the drug may have a reduced risk of death. But prior to the current study the mechanism of metformin’s action against pancreatic cancer was unclear, and no potential biomarkers of response to metformin had been reported. We have uncovered a novel mechanism behind the ability of the diabetes drug metformin to inhibit the progression of pancreatic cancer. Metformin decreases the inflammation and fibrosis characteristic of the most common form of pancreatic cancer. We found that metformin alleviates desmoplasia – an accumulation of dense connective tissue and tumor-associated immune cells that is a hallmark of pancreatic cancer – by inhibiting the activation of the pancreatic stellate cells that produce the extracellular matrix and by reprogramming immune cells to reduce inflammation. Our findings in cellular and animal models and in patient tumor samples also indicate that this beneficial effect may be most prevalent in overweight and obese patients, who appear to have tumors with increased fibrosis. (more…)
Author Interviews, Cancer Research / 14.01.2016

More on Protein Kinases on 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, Brigham & Women's - Harvard, Colon Cancer, Dermatology, Nature, Testosterone / 14.01.2016

More on Colon Cancer on Interview with: Dr. Nana Keum, PhD Department of Nutrition Harvard T.H. Chan School of Public Health Boston, MA Medical Research: What is the background for this study? What are the main findings? Dr. Keum: Male pattern baldness, the most common type of hair loss in men, is positively associated with androgens as well as IGF-1 and insulin, all of which are implicated in pathogenesis of colorectal neoplasia.  Therefore, it is biologically plausible that male pattern baldness, as a marker of underlying aberration in the regulation of the aforementioned hormones, may be associated with colorectal neoplasia.  In our study that examined the relationship between five male hair pattern at age 45 years (no-baldness, frontal-only-baldness, frontal-plus-mild-vertex-baldness, frontal-plus-moderate-vertex-baldness, and frontal-plus-severe-vertex-baldness) and the risk of colorectal adenoma and cancer, we found that frontal-only-baldness and frontal-plus-mild-vertex-baldness were associated with approximately 30% increased risk of colon cancer relative to no-baldness.  Frontal-only-baldness was also positively associated with colorectal adenoma. (more…)
Author Interviews, Breast Cancer, Nature, University Texas / 13.01.2016

Click Here for More Articles Related To Breast Cancer on Interview with: Dr. Chunru Lin PhD Assistant Professor, Department of Molecular and Cellular Oncology, Division of Basic Science Research and Graduate School of Biomedical Sciences The University of Texas MD Anderson Cancer Center, Houston, TX MedicalResearch: What is the background for this study? What are the main findings? Dr. Lin: Triple-Negative Breast Cancer (TNBC) continues to be a serious healthcare problem despite improvements in early detection and treatment; lncRNAs are one of the emerging elements that make the process of understanding breast cancer development and progression so complex yet thorough. Thus, it is imperative to include an examination of lncRNAs when studying breast cancer, especially when researching challenging questions related to relapses and recurrences of breast cancer that occur after targeted therapeutic treatments. A perspective that incorporates lncRNAs into the discussion of breast cancer biology could be the conceptual advance that is necessary to encourage further breakthroughs. Our research reveals the biological functional roles of cytoplasmic lncRNAs as signaling pathway mediators and catalysts that serve as indispensable components of signal transduction cascades and gene networks. This understanding could transform the prevailing dogma of the field of signal transduction. This study has identified a previously unknown mechanism for HIF stabilization and signal transduction, which is triggered by the HB-EGF bound EGFR/GPNMB heterodimer and is mediated by LINK-A-dependent recruitment of two kinases, BRK and LRRK2, to phosphorylate HIF1α at two new sites, leading to HIF1α stabilization and interaction with p300 for transcriptional activation; this further results in cancer glycolytic reprogramming under normoxic conditions. LINK-A is the first demonstrated lncRNA that acts as a key mediator of biological signaling pathways, which suggests the potential for the involvement of other lncRNAs as mediators of numerous signaling pathways. Importantly, expression of LINK-A and activation of the LINK-A mediated signaling pathway are both correlated with TNBC. Targeting LINK-A with LNAs (Locked Nucleic Acids) serves as an encouraging strategy to block reprogramming of glucose metabolism in TNBC with therapeutic potential.  (more…)
Author Interviews, Lung Cancer, Pharmacology / 12.01.2016 Interview with: Glen Weiss, MD, MBA Director of Clinical Research & Medical Oncologist and Dr. Zoltan Lohinai MD National Koranyi Institute of Pulmonology Budapest, Hungary Western Regional Medical Center Cancer Treatment Centers of America Goodyear, Arizona MedicalResearch: What is the background for this study? What are the main findings? Response: With nearly 1.4 million deaths each year, lung cancer is the world’s leading cause of cancer-related mortality. In the U.S., more than 162,000 die annually of this disease. One subtype of this cancer, small cell lung cancer (SCLC), is one of the most progressive tumor types. No new class of systemic treatment has been adopted as a new benchmark for standard therapy against SCLC for nearly three decades. Lung cancer researchers focus on SCLC not only because of its scientific challenge, but also because of their great desire to help patients suffering from this aggressive tumor. Drug repurposing bioinformatical analysis, a new research direction, has found that FDA-approved drugs in non-malignant diseases may have antitumor effects. Our study attempted to evaluate the recent laboratory findings in a clinical setting. Statins are a class of drugs primarily used to lower cholesterol in patients at risk for heart disease. They have been hypothesized by preclinical data to affect tumor cells through the extracellular signal-regulated kinase (ERK) pathway, which regulates many cellular functions. Our study of 876 metastatic-stage  small cell lung cancer patients, published Jan. 6, 2015, in the peer-reviewed scientific journal PLOS ONE, showed that statins appeared to provide an increase in overall survival for those cancer patients who were prescribed those medications. Patients prescribed other classes of drugs, including aspirin, antidepressants, and blood pressure-lowering agents, have reportedly shown anti-SCLC activity in previous preclinical studies. However, our study found no such survival benefits. All in all, our study is a good example of how to evaluate drug repurposing in oncology, and that statins might have clinical relevance in the treatment of SCLC. (more…)
Author Interviews, Biomarkers, Mayo Clinic, Prostate, Prostate Cancer, Urology / 12.01.2016 Interview with: R. Jeffrey Karnes MD Department of Urology, Mayo Clinic, Rochester, MN 55905   MedicalResearch: What is the background for this study? What are the main findings? Dr. Karnes: Cancer recurrence following radical prostatectomy is a concern for men undergoing definitive surgical treatment for prostate cancer. Approximately 20-35% of patients develop a rising prostate specific antigen following radical prostatectomy for clinically localized prostate cancer. PSA monitoring is an important tool for cancer surveillance; however, a standard PSA cutpoint to indicate biochemical recurrence has yet to be established. Over 60 different definitions have been described in literature. This variation creates confusion for the patients and clinicians. By studying a large group of patients who underwent radical prostatectomy at Mayo Clinic, we found that a PSA cutpoint of 0.4 ng/mL is the optimal definition for biochemical recurrence. (more…)
Annals Internal Medicine, Author Interviews, Breast Cancer, Mammograms / 12.01.2016 Interview with: Susan K. Boolbol, MD, FACS Chief, Division of Breast Surgery Chief, Appel-Venet Comprehensive Breast Service Co-Director, Breast Surgery Fellowship Mount Sinai Beth Israel Associate Professor of Surgery Icahn School of Medicine at Mount Sinai New York, NY 10003 Medical Research: What is the background for these new recommendations? Dr. Boolbol: To make this final recommendation, the Task Force conducted a comprehensive review of the science since its 2009 recommendation and considered the public comments it received on its 2015 draft recommendation statement. Based on all of this, the task force issued their recommendations. Medical Research: What are the main changes from current guidelines? Dr. Boolbol: Presently, there are several different guidelines and recommendations regarding screening mammography. Depending on the group issuing the guidelines, the recommendations vary from annual mammography beginning at 40 years old to biennial mammograms from 50 to 74 years old. The Task Force continues to find that the benefit of mammography increases with age, and recommends biennial screening in women ages 50 to 74. (more…)
Author Interviews, Cancer Research, JAMA, Transplantation / 11.01.2016 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, Dermatology, JAMA, Melanoma, Technology / 08.01.2016 Interview with: Marc Haspeslagh, MD Dermpat, Ardooie, Belgium Department of Dermatology University Hospital, Ghent, Belgium Medical Research: What is the background for this study? Dr. Haspeslagh: In daily practice, most pathology laboratories process skin biopsy specimens without access to the clinical and /or dermoscopic images. In pigmented skin tumors, this information can be crucial to process and diagnose the lesion correctly. With increasingly smaller diameter lesions undergoing biopsy, these focal changes are only visible with dermoscopy; therefore, communication of this dermoscopic information to the pathologist is important. In many dermatopathology laboratories, this communication is often insufficient or totally absent, and one can presume that these suspicious areas are often missed with the standard random sectioning technique that examines less than 2% of the tissue. To overcome this diagnostic limitation we developed in 2013 a new method for processing skin biopsies, were we routinely take an ex vivo dermoscopic image of most tumoral skin lesions. In combination with marking specific and suspected areas seen on the ex vivo dermoscopy (EVD) with nail varnish, EVD with derm dotting is a simple and easy method that brings this crucial information to the pathologist and in the slides to be examined (Am J Dermatopathol 2013; 35(8),867-869). (more…)
Author Interviews, Breast Cancer, Geriatrics, Mammograms / 07.01.2016 Interview with: Professor Charles Hennekens MD Dr.P.H Sir Richard Doll Professor Senior Academic Advisor to the Dean Charles E. Schmidt College of Medicine Florida Atlantic University 777 Glades Road Boca Raton, FL 33431 Medical Research: What is the background for this study? What are the main findings? Prof. Hennekens: Randomized evidence indicates clear benefits of mammography in middle age and, at present, most guidelines recommend regular mammography for women up to age 74.  In collaboration with colleagues at Baylor Medical College and Meharry Medical School we were able to link the Surveillance, Epidemiology, and End Results (SEER) data to the Medicare administrative claims data.  We found that, up to 84 years, screening was more common among whites than blacks and women receiving regular annual screening mammography had lower risks of mortality from breast cancer. (more…)
Author Interviews, Cancer Research, Heart Disease, Pediatrics / 07.01.2016 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 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, Dermatology, Melanoma, Surgical Research / 05.01.2016 Interview with: Jason B. Lee MD Professor , Clinical Vice Chair Department of Dermatology and Cutaneous Biology Director, Jefferson Dermatopathology Center Thomas Jefferson University Philadelphia, Pennsylvania  Medical Research: What is the background for this study? What are the main findings? Dr. Lee: When initially described, Clark et al. suggested that dysplastic nevi were intermediate lesions that lie biologically on a spectrum between benign and malignant. As such, they were to be histologically graded as mild, moderate, and severe (or a combination thereof), with mild presumably closer to benign and severe closer to malignant. In this paradigm, adopted by most dermatologists, these nevi are routinely excised based on histologic grading and margin status. Recent outcomes of follow-up and excision studies of dysplastic nevi suggest that they are over treated as there have been very low rates of melanoma on re-excision. An alternative approach considers dysplastic or eponymously Clark nevi as common acquired nevi, typically in fair skin individuals, and rejects the entire notion that they are intermediate lesions as there exists no formal proof of their intermediate status. This approach omits grading and margin status entirely, providing the clinician an explicit recommendation for excision only for those cases of diagnostic uncertainty. In this study, excision recommendation rate of dysplastic/Clark nevi was determined along with analysis of excision outcomes in a laboratory where non-grading histologic diagnostic approach to these nevi has been adopted. The excision recommendation rate, representing the diagnostic uncertainty rate, was 11.1%. Out of 80% of the cases returned for excision, only 2.0% of the cases were interpreted as melanoma on excision; all were in situ or thin melanomas. This excision rate is much lower than in prior reports, which vary from 22-52%, while still capturing melanomas within this subset of lesions. (more…)
Author Interviews, Prostate Cancer, Race/Ethnic Diversity / 04.01.2016 Interview with: Benjamin A. Rybicki, Ph.D Department of Public Health Sciences Henry Ford Health System Detroit, MI  Medical Research: What is the background for this study? What are the main findings? Dr. Rybicki: Inflammation of the prostate gland—prostatitis—is a complex and heterogeneous condition. Two separate meta-analyses have estimated about a 60% increased risk of prostate cancer associated with clinical prostatitis.  Most prostatitis, however, is asymptomatic and not fully captured in prevalence surveys. In fact, over 50% of surgical prostate specimens demonstrate some histological evidence of chronic inflammation, which has been generally shown to decrease risk of prostate cancer. The race of a patient may also be a factor as far as how inflammation influences prostate cancer risk. African American men are at greater risk for prostate cancer and demonstrate higher levels of circulating prostate specific antigen (PSA), which can confound the relationship between inflammation and prostate cancer. In adjusted analyses, African American men with clinical chronic prostatitis had a significant 53% decreased risk of prostate cancer compared with African American men without prostatitis. Clinical prostatitis did not significantly increase prostate cancer risk in white men overall, but it was associated with a significant 3.5-fold increased risk in those who had no evidence of histologic prostatic inflammation. In addition, the investigators found that clinical prostatitis increased prostate cancer risk nearly 3-fold in white men with a low PSA velocity and nearly 2-fold in white men with more frequent PSA testing. PSA level and PSA density did not significantly modify the effect of clinical prostatitis on prostate cancer risk. (more…)
Author Interviews, Brigham & Women's - Harvard, JAMA, Prostate Cancer, Surgical Research, Testosterone / 04.01.2016 Interview with: Quoc-Dien Trinh MD Assistant Professor, Harvard Medical School Brigham and Williams Hospital  Medical Research: What is the background for this study? What are the main findings? Dr. Trinh: Among elderly Medicare beneficiaries with metastatic prostate cancer, surgical castration is associated with lower risks of any fractures, peripheral arterial disease, and cardiac-related complications compared to medical castration using GnRH agonists. (more…)
Author Interviews, Breast Cancer, Immunotherapy, PLoS / 02.01.2016 Interview with: David Gallego Ortega, PhD Group Leader, Tumour Development Group Cancer Division Garvan Institute of Medical Research Conjoint Lecturer, St Vincent’s Clinical School, Faculty of Medicine, UNSW, Australia National Breast Cancer Foundation and Cure Cancer Foundation Australia Fellow  Medical Research: What is the background for this study? What are the main findings? Dr. Ortega: We have identified a protein that 'goes rogue’ in breast cancer. The protein, called Elf5, ‘tricks' the immune system producing inflammation so that the immune cells now help the breast cancer cells to spread throughout the body. Cancer spread, or metastasis, is the ultimate cause of death of breast cancer patients, so we are very excited about our discovery because it opens the door to explore anti-inflammatory drugs that can be combined with existing therapies. We have found that luminal breast cancer patients that present high levels of Elf5 progress earlier in their disease. The Luminal subtype is the most common type of breast cancer, so these therapies will potentially benefit to 2/3 of all breast cancer patients. (more…)
Author Interviews, CT Scanning, JAMA, Lung Cancer / 02.01.2016 Interview with: Jan Marie Eberth, PhD Assistant Professor, Department of Epidemiology and Biostatistics Deputy Director, SC Rural Health Research Center Core Faculty, Statewide Cancer Prevention and Control Program Arnold School of Public Health University of South Carolina Columbia, SC 29208 Medical Research: What is the background for this study? Dr. Eberth: With the breakthrough findings of the National Lung Screening Trial released in 2011, professional organizations have largely embraced population-based screening guidelines for patients at high risk for lung cancer. The diffusion of screening into broad clinical practice has been slow to be adopted, given concerns about the efficacy of screening in community settings, lack of insurance reimbursement and unclear billing logistics, and difficulty weighing the pros of screening against the known cons (e.g., high rate of false positives). Medical Research: What are the main findings? Dr. Eberth: Provisions of the Patient Protection and Affordable Care Act mandate that US Preventive Services Task Force-recommended screening tests with an A or B rating receive full insurance coverage by private payers. The Centers for Medicare and Medicaid (CMS) soon thereafter approved full coverage for lung cancer screening in high-risk patients (i.e., those aged 55-77 years, asymptomatic for lung cancer, tobacco smoking history of 30+ pack-years, is a current smoker or has quit smoking within the past 15 years). Coding is rapidly evolving; as of November 2015, CMS released HCPCS codes G0296 (pre-screening counseling visit) and G0297 (screening visit). These codes will be accepted retroactively starting January 4, 2016 to the date of the final coverage determination (back to February 5, 2015). No coinsurance or deductibles shall be charged to the patient for either the pre-screening counseling visit, or the screening visit itself. Quality of screening  is an important, but understudied, area of research. Several publications have focused on aspects of quality programs, and how to achieve quality benchmarks, but data is still being collected to assess variation across programs. In the future, data from screening registries, such as the American College of Radiology Lung Cancer Screening Registry (LCSR), can be leveraged to examine these quality metrics and improve risk-prediction models for lung cancer. (more…)
Author Interviews, Breast Cancer, Stem Cells / 29.12.2015 Interview with: Jenny C. Chang, M.D. Director, Houston Methodist Cancer Center Professor of Medicine, Weill Cornell Medical College Full Member, Houston Methodist Research Institute Houston, Texas  MedicalResearch: What is the background for this study? What are the main findings? Dr. Chang: The current treatment of triple negative breast cancer, which accounts for about 15% of all cases of breast cancer, is still based on surgery, radiotherapy, and classic chemotherapy because, unlike other types of breast cancer, it is not amenable to hormonal or targeted therapy. However, research findings suggest that cancer stem cells, which represent about 2% of all neoplastic cells, may play a role in disease relapses and the formation of distant metastases. As these cells may represent a therapeutic target, the aim of this study is to modify the micro-environment in which they reproduce by acting directly on the chemokines involved in inflammation because there is evidence indicating a possible mechanism of action of reparixin, a molecule developed by Dompé, an Italian biopharmaceutical company, in the targeted treatment of these cancers. (more…)
Author Interviews, Brigham & Women's - Harvard, End of Life Care, JAMA, Leukemia / 28.12.2015 Interview with: Oreofe O. Odejide, MD Instructor in Medicine, Harvard Medical School Dana-Farber Cancer Institute Medical Research: What is the background for this study? What are the main findings? Dr. Odejide: The care that patients with hematologic cancers receive near the end of life is distinct from patients with solid tumors. For instance, previous research has shown that patients with blood cancers are more likely to receive intensive care at the end of life such as chemotherapy within 14 days of death, intensive care unit admission within 30 days of death, and they are less likely to enroll in hospice. My colleagues and I hypothesized that timing of discussions regarding end-of-life preferences with patients may contribute to these findings, and we wanted to examine hematologic oncologists’ perspectives regarding end-of-life discussions with this patient population. We conducted a survey of a national sample of hematologic oncologists obtained from the publicly available clinical directory of the American Society of Hematology. We received responses from 349 hematologic oncologists, giving us a response rate of 57.3%. In our survey, we asked hematologic oncologists about the typical timing of EOL discussions in general, and also about the timing of the first discussion regarding resuscitation status, hospice care, and preferred site of death for patients. Three main findings emerged:
  • First, the majority of hematologic oncologists (56%) reported that typical EOL discussions occur “too late.”
  • Second, hematologic oncologists practicing primarily in tertiary care settings were more likely to report late discussions compared to those in community settings.
  • Third, a substantial proportion of respondents reported that they typically conduct the initial discussions regarding resuscitation status, hospice care, and preferred site of death at less optimal times.
Author Interviews, Breast Cancer, Cancer Research, Chemotherapy, JAMA / 24.12.2015 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, Lymphoma, NEJM / 24.12.2015 Interview with: Dr. Michael van Leeuwen PhD Department of Epidemiology Netherlands Cancer Institute Amsterdam, the Netherlands Medical Research: What is the background for this study? What are the main findings? Response: Over the last decades cure rates for Hodgkin’s lymphoma patients have increased dramatically. Cure and long-term survival may, however, come at a price, in the form of an increased risk of second cancers and other late effects. Since the late 1980’s treatment of Hodgkin’s lymphoma has been changed towards smaller radiation target volumes and more effective, generally less toxic chemotherapy. In a study which included 3905 Hodgkin’s lymphoma patients treated between 1965 and 2000 in the Netherlands, the impact of these treatment changes on second malignancy risk was evaluated. Hodgkin’s lymphoma patients were between the ages of 15 and 50 years and had survived at least 5 years after treatment. During follow-up, 1055 second cancers were diagnosed in 908 survivors, corresponding to a risk of 4.6 times as high as the occurrence of cancer in the general population. Up to at least 40 years after treatment for Hodgkin’s lymphoma, survivors remained at increased risk for second cancers. The cumulative incidence of a second cancer was 33.2% at 30 years, compared with 9.6% in the general population, and 48.5% at 40 years, compared with 19.0% in the general population. Breast cancer was the most common second cancer reported followed by lung and gastrointestinal cancers. Thirty-year cumulative incidence was 16.6% for breast cancer, 7.1% for lower respiratory tract cancers, 7.0% for gastrointestinal cancers, and 3.7% for non-Hodgkin’s lymphomas. The risk of solid cancer after treatment for Hodgkin’s lymphoma was not lower among more recently treated patients (patients treated between 1989 and 2000) than among those who were treated in earlier time periods, despite changes in treatment. Nonetheless, patients treated with smaller radiation fields (e.g., a supradiaphragmatic field radiotherapy not including the axilla) were at a 63% lower relative risk of breast cancer as a second malignancy than if they received complete mantle-field radiotherapy. The lack of change in the cumulative incidence of solid cancers could be due to an incomplete adoption of the more modern radiotherapy concepts but may also be explained on the basis of a change in the chemotherapy regimens used in the 1990s. Because in the 1970’s many women exposed to high doses of alkylating agents were experiencing premature menopause, doses of alkylating agents were lowered over time to preserve fertility. However, early menopause introduced with the alkylating regimens was likely responsible for decreasing the breast cancer incidence. With the lower doses of the alkylating agents, this protection was taken away. The cumulative incidence of non-Hodgkin’s lymphoma and of leukemia (and the myelodysplastic syndrome) was, however, much lower among patients who were treated in the period from 1989 through 2000 than among those who were treated in the period from 1965 through 1976. For leukemia, the decrease in cumulative incidence is likely due to the much lower doses of alkylating agents used in Hodgkin’s lymphoma treatment in the 1990’s compared to earlier decades. It is important to realize that current common practice in radiation oncology, including involved-node or involved-site radiotherapy, three-dimensional conformal radiation treatment planning, and radiation doses of less than 36 Gy, was not applied in our study population. It is hoped that these changes may reduce the risk of solid cancer among patients treated after 2000. (more…)
Author Interviews, Cancer Research, Prostate Cancer, Surgical Research, Transplantation / 23.12.2015 Interview with: Gerardo Vitiello, MD Emory University School of Medicine Emory Transplant Center NYU Langone Medical Center Department of Surgery  Medical Research: What is the background for this study? What are the main findings? Dr. Vitiello:   Screening for prostate cancer with prostate specific antigen (PSA) levels is highly controversial, as it is a non-specific marker for prostate cancer. A PSA level may be elevated in a variety of disease processes (not only prostate cancer), and even in the general population, the benefit of early intervention for prostate cancer is unclear. In contrast, end stage renal disease (ESRD), where patients no longer have renal function and require dialysis, is a major health problem with a huge impact on a patient’s quality of life. The only cure for ESRD is kidney transplantation, which has been shown to have an enormous health and quality of life benefit for transplant recipients. Transplant centers have rigorously screened candidates for potential malignancy prior to transplantation to ensure that there are no contraindications to receiving a transplant. For the first time, we demonstrate that screening for prostate cancer in kidney transplant candidates is not beneficial, and may actually be harmful, since it delays time to transplant and reduces a patient’s chance of receiving a transplant without an apparent benefit on patient survival. (more…)
Author Interviews, Breast Cancer, Genetic Research, Journal Clinical Oncology / 23.12.2015 Interview with: Dr. Marjanka Schmidt PhD Group Leader, Molecular Pathology Netherlands Cancer Institute Medical Research: What is the background for this study? What are the main findings? Dr. Schmidt: BRCA1/2 mutation carriers who developed a primary breast cancer are thought to be at high risk to develop a contralateral breast cancer (breast cancer in the opposite breast). Our study is one of the first to provide unbiased risk estimates for young breast cancer patients with a pathogenic BRCA1/2 mutation. We also showed that age of onset of the first breast cancer is a predictor for the development of contralateral breast cancer in BRCA1/2 mutation carriers, but not in non-carriers. (more…)
Author Interviews, Cancer Research, Colon Cancer, Cost of Health Care, JAMA, Social Issues, University of Michigan / 23.12.2015 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…)