Author Interviews, Cancer Research, JAMA, MD Anderson, Outcomes & Safety / 12.02.2015

Kenneth L. Kehl, MD Division of Cancer Medicine, MD Anderson Cancer Center Houston, TexasMedicalResearch.com Interview with: Kenneth L. Kehl, MD Division of Cancer Medicine, MD Anderson Cancer Center Houston, Texas Medical Research: What is the background for this study? What are the main findings? Response: Prior studies have demonstrated that most patients with cancer wish to participate in their treatment decisions.  We studied a cohort of patients with lung or colorectal cancer and assessed whether patient involvement in decision-making was associated with perceived quality of care or ratings of physician communication.  We found that patients who described a more shared decision-making process gave higher ratings of their care quality and physician communication.  This effect was independent of patients' stated preferences regarding involvement in decision-making. (more…)
Author Interviews, Cancer Research, Critical Care - Intensive Care - ICUs, Infections / 12.02.2015

Dr. Cornejo-Juárez Department of Infectious Disease, Instituto Nacional de Cancerología Tlalpan MexicoMedicalResearch.com Interview with: Dr. Cornejo-Juárez Department of Infectious Disease, Instituto Nacional de Cancerología Tlalpan Mexico MedicalResearch: What is the background for this study? Dr. Cornejo: Critically ill patients in the intensive care unit are at major risk of hospital-acquired infections. Immunosuppressed patients have a higher risk related with continuous exposure to the hospital setting, mucositis and disruption of skin integrity, presence of indwelling catheters and abnormal immune system because of primary malignancy or chemotherapy. Our aimed was to investigate prevalence and outcome of hospital-acquired infections in an oncology ICU. MedicalResearch: What are the main findings? Dr. Cornejo: We found that hospital-acquired infections are a major problem in the ICU. Hospital-acquired infections are related with higher mortality. Multidrug resistant bacteria are frequently involved in these infections, and are associated with increased mortality. (more…)
Author Interviews, Genetic Research, Leukemia, NEJM, Personalized Medicine / 11.02.2015

David G. Kent, Ph.D From the Cambridge Institute for Medical Research and Wellcome Trust–Medical Research Council Stem Cell Institute University of CambridgeMedicalResearch.com Interview with: David G. Kent, Ph.D From the Cambridge Institute for Medical Research and Wellcome Trust–Medical Research Council Stem Cell Institute University of Cambridge Medical Research: What is the background for this study? What are the main findings? Dr. Kent: Cancers are the result of the sequential acquisition of errors in the genetic code.  Most studies have focused on the sum of these mutations (e.g., A+B+C = cancer) but no study in patients has asked the question of whether or not the order of genetic mutations impacts the disease (e.g., does A to AB equal B to BA).  We studied patients with chronic blood disorders (known as myeloproliferative neoplasms, or MPNs) that are precursors to cancer to access the earliest stages of tumour development and studied whether or not the order of mutation acquisition impacted disease.  We studied patients with mutations in two genes (JAK2 and TET2) and showed that the order of acquisition of these mutations impacted timing of clinical presentation, disease subtype, frequency of thrombotic events, and differed in their response to targeted therapy in the lab. (more…)
Author Interviews, Cancer Research, NEJM, Thyroid / 11.02.2015

Dr. Martin S. Schlumberger MD Department of Nuclear Medicine and Endocrine Oncology Centre de Référence Tumeurs Réfractaires de la Thyroïde Institut Gustave Roussy and University Paris-Sud Villejuif, FranceMedicalResearch.com Interview with: Dr. Martin S. Schlumberger MD Department of Nuclear Medicine and Endocrine Oncology Centre de Référence Tumeurs Réfractaires de la Thyroïde Institut Gustave Roussy and University Paris-Sud Villejuif, France   Medical Research: What is the background for this study? What are the main findings? Dr. Schlumberger: Patients with advanced refractory thyroid cancer is rare (4-5 patients/million population) but portends a poor prognosis with a median overall survival of 3-5 years from the diagnosis of metastases. Before the availability of kinase inhibitors there was no effective treatment, and for this reason placebo was used as control in SELECT trial. This trial showed an improvement of PFS lenvatinib vs placebo (hazard ratio: 0.21; 99% CI: 0.14–0.31, P<0.001; median PFS: 18.3 vs 3.6 months, respectively) and objective response rate of 65% with some complete responses. Time to response was short (2 months). Similar benefits were observed in naive patients and in patients who had been treated with another tyrosine kinase inhibitor, demonstrating the absence of cross resistance. Toxicity was significant and could be controlled with dose reduction and symptomatic treatment. Medical Research: What should clinicians and patients take away from your report? (more…)
Author Interviews, Breast Cancer / 11.02.2015

Alejandra Valenzuela-IglesiasMedicalResearch.com Interview with: Alejandra Valenzuela-Iglesias Ph.D. candidate Department of Molecular Biology University of Sonora Hermosillo, Sonora MedicalResearch: What is the background for this study? What are the main findings? Response: Breast cancer is one of the leading causes of cancer death in women all around the world. In recent years, there has been great interest in creating new therapies that will help to prevent or stop metastasis, but the therapies developed up until today are not completely effective. Metastasis is the main cause of death for a cancer patient because it implies that tumor cells have detached from the primary tumor and have colonized in one or more vital organs or tissues in the organism. For this to occur, the invasive tumor cells form actin-driven membrane protrusions called invadopodia. These protrusions possess proteolytic activity to degrade the basal membrane and extracellular matrix, which facilitates metastatic cancer cells to enter the bloodstream and spread to distant organs in the body. It has been shown that any dysregulation in the actin cytoskeleton leads to impaired invadopodia formation. Profilin1, an actin and phosphoinositide binding protein, is downregulated in several adenocarcinomas. Our study was a collaboration between Albert Einstein College of Medicine, University of Pittsburgh, and University of Sonora, lead by Dr. Jose Javier Bravo-Cordero and published in the European Journal of Cell Biology. We showed for the first time the role of profilin1 in invadopodia formation and function in human breast cancer cells MDA-MB-231. By using cell imaging techniques we unveiled the dynamic of the profilin1-depleted cells, finding that profilin1 can act as a negative regulator of breast cancer cell invasion, acting as a break in invadopodia turnover, by modulating the molecules involved in invadopodia maturation. The removal of profilin1 expression accelerates invadopodia maturation rate, explaining the invasive phenotype previously reported for this type of cells. (more…)
Author Interviews, Cancer Research / 11.02.2015

MedicalResearch.com Interview with: Dr. Dixie-Lee Esseltine MD, FRCPC Vice President, Oncology Clinical Research Takeda. MedicalResearch: What is Ixazomib? Dr. Dixie-Lee Esseltine: Ixazomib is an investigational, oral, once-weekly proteasome inhibitor (PI) that is being investigated in multiple Phase 3 trials in multiple myeloma (MM) and systemic light-chain (AL) amyloidosis. It is the first oral  proteasome inhibitor to enter Phase 3 clinical trials. Proteasome inhibition is a mechanism underpinning an established standard of care in the treatment of multiple myeloma. However, the current biweekly parenteral administration of proteasome inhibitors may pose challenges to patients. The ability to demonstrate that an oral, once-weekly PI can extend PFS would be a remarkably important finding in the effort to address these challenges. Early studies suggest ixazomib, has activity in MM patients, both as a single agent in relapsed patients and in combination in frontline patients. Ixazomib was granted orphan drug designation in multiple myeloma in both the U.S. and Europe in 2011, and for AL amyloidosis in both the U.S. and Europe in 2012. It was granted Breakthrough Therapy Designation for AL amyloidosis in the U.S. in 2014. MedicalResearch: What is the design for this study? Dr. Dixie-Lee Esseltine: The TOURMALINE MM-1 study (C16010) is a phase 3, randomized, double-blind study comparing ixazomib plus lenalidomide and dexamethasone versus placebo plus lenalidomide and dexamethasone in patients with relapsed and/or refractory multiple myeloma. Patients were randomized to receive ixazomib 4.0mg days 1,8 and 15 or placebo with  lenalidomide 25mg days 1-21 and dexamethasone 40mg days 1,8,15 and 22. Treatment was given every 28 days until disease progression or unacceptable toxicity. Evaluation was based on the International Myeloma Working Group (IMWG) Uniform Response Criteria. (more…)
Author Interviews, Baylor College of Medicine Houston, Breast Cancer / 10.02.2015

Dr. Xiang (Shawn) Zhang PhD Assistant Professor Department of Molecular and Cellular Biology Lester and Sue Smith Breast Center Baylor College of Medicine Houston, TexasMedicalResearch.com Interview with: Dr. Xiang (Shawn) Zhang PhD Assistant Professor Department of Molecular and Cellular Biology Lester and Sue Smith Breast Center Baylor College of Medicine Houston, Texas   Medical Research: What is the background for this study? What are the main findings? Response: Bone metastases present a major clinical problem for oncologists. They are very painful and unpleasant due to the ability of metastatic cells to dissolve bones, and if they spread to the spine or vertebrate bone they  the spinal cord compression could cause paralysis. There is a gap in our knowledge about bone metastasis in breast cancer. We know a lot about when they are fully established and already dissolving the bone, but little about what happens early on, right after the cancer cells get there but before they start the bone-dissolving process. In the study, we revealed that in the early stages, when there are only a few cancer cells, these cells tend to locate themselves in a microenvironment that is enriched in bone making cells called osteoblasts whose normal job is to help make new bones. The cancer cells appear to be surrounded by these bone-making cells before they acquire the ability to dissolve bones. We also uncovered the pathway that gets activated when the cancer cells lodge into the bone-making cells, and helps them progress to more malignant metastases. The action is mediated by a class of proteins that helps bind the cancer cells to the bone tissue called heterotypic adherens junctions (hAJs) involving the adherens proteins E-cadherin (cancer-derived) and N-cadherin (bone-promoting). This then activates the mTOR pathway in cancer cells, which drives the progression from single cells to metastases. (more…)
Author Interviews, Biomarkers, Lung Cancer / 06.02.2015

MedicalResearch.com Interview with: Teresa W-M. Fan PhD and Andrew N Lane, PhD Markey Cancer Center, University of Kentucky Medical Research: What is the background for this study? What are the main findings? Response:  The study began about eight years ago at the University of Louisville as a collaboration between thoracic surgeon Michael Bousamra II, immunologist Jun Yan and our metabolomics team (T. Fan, R Higashi and A.N. Lane) now at the U. Kentucky. Lung cancer remains as the highest cancer mortality in North America, and is unfortunately often not diagnosed until the most successful treatment, surgery, is no longer an option.  Furthermore although there are numerous subtypes of the disease, the options for chemotherapy are quite limited. We wanted to know how the biochemistry of early stage (resectable) lung cancer differs from that of healthy or at least non-cancerous lung tissue from the point of view of basic tumor biology, and whether we might uncover better option for therapeutic intervention. To this end, we applied our stable isotope resolved metabolomics (SIRM) technique directly to patients who were diagnosed with resectable NSCLC. By this technique, the fate of individual atoms from a non-radioactive enriched precursor (C-13 glucose in this instance) are traced as they are taken up from the blood and metabolized in situ. This technique, along with model studies with mice, isolated cell cultures, and so-called “Warburg” slices provides tremendous detail about the functional biochemistry of a cancer within its natural microenvironments, compared with non-cancerous tissue. The major finding published in this article is that the anaplerotic enzyme pyruvate carboxylase is greatly upregulated in NSCLC compared with paired non-cancerous lung tissue, whereas the other commonly utilized anaplerotic enzyme glutaminase was not. Interestingly, only cancer cells showed strong staining for pyruvate carboxylase, whereas in the paired non-cancerous lung tissue, only resident macrophages stained for PC. Pyruvate carboxylase was further shown to be essential for tumor growth in both call culture and in mouse xenografts. (more…)
Author Interviews, Breast Cancer, NYU / 05.02.2015

Agnel Sfeir PhD Assistant Professor Skirball Institute - NYU New York, NY 10016MedicalResearch.com Interview with: Agnel Sfeir PhD Assistant Professor  Skirball Institute - NYU New York, NY 10016 Medical Research: What is the background for this study? What are the main findings? Dr. Sfeir: The main finding of this study, published in the journal Nature, is that inhibiting the action of a particular enzyme dramatically slows the growth of tumor cells tied to BRCA1 and BRCA2 genetic mutations which, in turn, are closely tied to breast and ovarian cancers. This discovery about the enzyme — called polymerase theta, or PolQ — resulted from efforts to answer a fundamental biological question: How do cells prevent the telomere ends of linear chromosomes, which house our genetic material, from sticking together? Cell DNA repair mechanisms can stitch together telomeres broken as part of cell metabolism. But such fusions, the researchers say, compromise normal cell growth and survival. In the purest biological sense, our findings (in experiments in mice and human cells) show how this particular enzyme, which we know is active in several tumors, promotes unwanted telomere fusions by inserting whole segments of DNA via a disruptive DNA repair pathway termed alt-NHEJ. It was quite remarkable to find that by blocking PolQ action, cancer cell growth was cut by more than half. Additional experiments confirmed that PolQ is needed to activate the alt-NHEJ pathway of DNA repair. Unlike the main, error-free pathway — or HDR pathway — the alt-NHEJ pathway does not use a related chromosome’s genetic material as a template to meticulously correct any damaged genetic material. As such, alt-NHEJ is highly likely to leave coding mistakes. (more…)
Author Interviews, Cancer Research, Pediatrics / 02.02.2015

MedicalResearch.com Interview with: Kate A O’Neill Department of Paediatrics University of Oxford Children’s Hospital John Radcliffe Hospital Oxford UK MedicalResearch.com: What is the background for this study? Dr. O'Neill: Cancer affects around 1 in 500 children under the age of 15. Although the diagnosis and treatment of these diseases have seen major advances over the past few decades, survivors often experience health complications later in life, and cancer remains the main cause of disease related death in children in the developed world. The identification of risk factors for a number of adult cancers has allowed awareness and screening campaigns aimed at preventing disease. For the majority of childhood cancers, however, we still do not know what causes them, and so similar preventative measures are at present not possible. Incidence rates for many childhood cancers peak within the first few years of life, suggesting that the causative events occur early. For childhood leukaemia, it has even been shown that pre-malignant cells are already present at birth, indicating the disease may originate in utero. Studies exploring potential prenatal risk factors for childhood leukaemia have consistently found that children with the disease have higher birthweights than children who do not, and it is now widely accepted that the faster a foetus grows, the higher the risk of developing leukaemia in childhood. Leukaemia is the most common childhood cancer, accounting for approximately one third of all cases. Other childhood cancers are rarer, and it is consequently harder to perform similar risk association studies. The aim of this study was to compile information on large enough numbers of cases and controls to allow the analysis of risk associations between birthweight and all types of childhood cancer. Furthermore, we compiled data in different countries (USA and UK) to allow the comparison of results from two independent populations. MedicalResearch.com: What are the main findings? Dr. O'Neill: We found that with each 0.5kg (1.1lb) increase in birthweight, the risk of childhood cancer increased by 6%. Compared to babies with average birthweights (3-3.49kg, or 6.6lb -7.7lb), babies with clinically high birthweights (4kg, or 8.8lb, and above) had an increased risk of between 16% and 20%. These increased risks were strongest for certain cancers:
  • Leukaemias
  • Tumours of the central nervous system
  • Renal tumours
  • Soft tissue sarcoma
  • Neuroblastoma
  • Lymphoma
  • Germ cell tumours
  • Malignant melanomas
Hepatic tumours showed the reverse association, with risk increasing as birthweight decreased. Retinoblastoma, an embryonal tumour, and malignant bone tumours, which occur predominantly in adolescents, did not associate with birthweight. Our results were strikingly similar between USA and UK populations. Furthermore, birthweight appeared act independently of other factors that are known or suspected to associate with birthweight and/or childhood cancer (gestational age, birth order, plurality, maternal age and race/ethnicity). In summary, we found that approximately half of all childhood cancers are associated with birthweight. The association with a diversity of otherwise unrelated cancers indicates that in utero tissue growth and development has an underlying and potentially key role in the development of malignancy in childhood. (more…)
Author Interviews, Cancer Research, Psychological Science / 31.01.2015

Miss Charlotte Vrinten, MSc, BA, BSc Research psychologist Cancer Research UK Health Behaviour Research Centre Department of Epidemiology and Public Health University College LondonMedicalResearch.com Interview with: Miss Charlotte Vrinten, MSc, BA, BSc Research psychologist Cancer Research UK Health Behaviour Research Centre Department of Epidemiology and Public Health University College London Medical Research: What is the background for this study? What are the main findings? Response: Many people are afraid of getting cancer, but fear doesn’t have the same effect on everyone.  For some people, cancer fear motivates them to get checked up, for others it puts them off finding out whether they have cancer.  No-one before has worked out why fear might have such opposite effects.  We hypothesized that it might be due to how people experience fear, because some fearful people tend to worry a lot about cancer, while others feel physically uncomfortable thinking about it.  In our study, instead of using a combined measure of cancer fear as is often done, we distinguished these different aspects of fear to see whether they had different effects on people’s decisions about cancer screening.  We found that the effect of cancer fear depended on the type of fear: worriers were more likely to want to get screened for colon cancer, but those who felt uncomfortable thinking about cancer were 12% less likely to go for the test. Twelve percent may not seem like a lot, but given that tens of thousands of people are eligible for this type of screening, it means a big difference in the number of people actually having the test. (more…)
Author Interviews, Colon Cancer, Journal Clinical Oncology, Race/Ethnic Diversity, Stanford, Surgical Research / 30.01.2015

Kim F. Rhoads, MD, MS, MPH, FACS Assistant Professor of Surgery Director, Community Partnership Program Stanford Cancer Institute Unit Based Medical Director, E3 Surgery and Surgical Subspecialties Stanford University Stanford, Ca 94305MedicalResearch.com Interview with: Kim F. Rhoads, MD, MS, MPH, FACS Assistant Professor of Surgery Director, Community Partnership Program Stanford Cancer Institute Unit Based Medical Director, E3 Surgery and Surgical Subspecialties Stanford University Stanford, Ca 94305 Medical Research: What is the background for this study? What are the main findings? Dr. Rhoads: Colon cancer is the 3rd most common cancer in US men and women and is the 2nd most common cause of cancer death. For at least 2 decades, minorities with colon cancer have suffered a 15-20% additional risk of death when compared with non-minority patients. Our study set out to understand the influence of the location where treatment was delivered and the quality of care received, on overall survival and racial disparities. We examined more than 30,000 patients who were diagnosed and treated for colon cancer in California from 2001 through 2006.  Using cancer registry data linked to state level inpatient data and hospital information, we compared the rates of National Comprehensive Cancer Network (NCCN) guideline adherence and mortality by location of care and by race. We found that patients treated within an integrated health system (IHS) received NCCN guideline based care at higher rates than those treated outside the system—about 3% higher rates of surgery; and more than 20% higher rates of stage appropriate chemotherapy. The rates of guideline based care were nearly equal between the racial groups treated inside the IHS.  Propensity score matched comparisons revealed a lower risk of death for all patients and no racial disparities associated with treatment within the Integrated system.  For patients treated outside IHS, the disparity in mortality was explained by accounting for differences in receipt of evidence based care by race. (more…)
Author Interviews, Breast Cancer, Journal Clinical Oncology, Mayo Clinic / 30.01.2015

MedicalResearch.com Interview with: Dr. Amy C. Degnim MD Professor of Surgery Mayo Clinic, Rochester.Dr.  Amy C. Degnim MD Professor of Surgery Mayo Clinic, Rochester. Medical Research: What is the background for this study? What are the main findings? Dr. Hartmann: Approximately 1 million women in the US every year have a breast biopsy that shows benign findings. We have found that the specific features of the breast tissue seen under the microscope can help to predict the risk of breast cancer in the future.  We developed a mathematical formula to calculate breast cancer risk based on the features seen in the biopsy tissue (named the BBD-BC model).  We found that using these microscopic features provides more accurate predictions of risk than the previous standard- the Breast Cancer Risk Assessment Tool (BCRAT). (more…)
Author Interviews, Nature, Ovarian Cancer / 29.01.2015

Dr. Terry Magnuson PhD Vice Dean for Research Department of Genetics, School of Medicine University of North Carolina at Chapel Hill Chapel Hill, North Carolina 27599MedicalResearch.com Interview with: Dr. Terry Magnuson PhD Vice Dean for Research Department of Genetics, School of Medicine University of North Carolina at Chapel Hill Chapel Hill, North Carolina 27599 Medical Research: What is the background for this study? What are the main findings? Response: Ovarian clear-cell carcinoma is a lethal form of ovarian cancer with limited therapeutic options. Recent patient-derived tumor sequencing studies support a strong genetic basis for the disease, but the roles of gene mutations in cancer causation are still unclear. We observed rapid induction of ovarian clear-cell carcinoma in mice that were genetically engineered to carry mutations in ARID1A and PIK3CA−the two most frequently mutated genes. Comparisons between human and mouse tumors uncovered a downstream role for the Interleukin-6 (IL-6) cytokine-signaling pathway in tumor progression. Thus, ARID1A and PIK3CA mutations cause ovarian clear-cell carcinoma and promote tumor cell growth by acting upon the IL-6 signaling pathway. (more…)
Author Interviews, Breast Cancer / 29.01.2015

William J. Brackenbury, Ph.D. MRC Fellow Department of Biology University of York, Heslington, York UKMedicalResearch.com Interview with: William J. Brackenbury, Ph.D. MRC Fellow Department of Biology University of York, Heslington, York UK Medical Research: What is the background for this study? Dr. Brackenbury: Metastasis, the spread of cancer cells from the primary tumour to secondary sites, e.g. the lungs or bones, is the main cause of deaths from cancer. However, there are no effective treatments available to slow or stop this devastating aspect of the disease. We and others have found that sodium channels, normally present in neurons and muscle cells, are up-regulated in metastatic breast cancer cells. Sodium channels appear to regulate the behaviour of these cancer cells, helping them to move and squeeze their way out of the primary tumour as they invade and metastasise on their way to distant sites. This suggests that sodium channels might be useful new therapeutic targets for drugs that could slow metastasis. Medical Research: What are the main findings? Dr. Brackenbury: Sodium channels are important drug targets for treating epilepsy. We have found that the antiepileptic drug phenytoin, which is a sodium channel blocker, reduces tumour growth and metastasis in a preclinical model of breast cancer. We found that phenytoin reduces proliferation of cancer cells within the primary tumour. It also reduces local invasion of cancer cells into the surrounding fat and muscle, and reduces the number of cells metastasising to distant sites in the liver, lungs and spleen. (more…)
Author Interviews, General Medicine, Journal Clinical Oncology, Leukemia, Pediatrics / 29.01.2015

MedicalResearch.com Interview with: Jun J. Yang  Ph.D. Assistant Member Dept. of Pharm. Sci. St. Jude Children's Research Hospital Memphis, TN 38105 Medical Research: What is the background for this study? What are the main findings? Dr. Yang: Mercaptopurine is highly effective in acute lymphoblastic leukemia (ALL) and essential for the cure of this aggressive cancer. However, it also has a narrow therapeutic index with common toxicities. Identifying genetic risk factors for mercaptopurine toxicity will help us better understand how this drug works and also potentially enable clinicians to individualize therapy based on patients’ genetic make-up (precision medicine). In addition to confirming the role of TPMT, we have identified another important genetic risk factor (a genetic variation in a gene called NUDT15) for mercaptopurine intolerance. Patients carrying the variant version of NUDT15 are exquisitely sensitive and required up to 90% reduction of the normal dose of this drug. TPMT variants are more common in individuals of African and European ancestry, whereas NUDT15 variants are important in East Asians and Hispanics. (more…)
Author Interviews, JAMA, Prostate Cancer, Radiology / 29.01.2015

MedicalResearch.com Interview with: Mohummad Minhaj Siddiqui, MD AssiMohummad Minhaj Siddiqui, MD Assistant Professor of Surgery - Urology Director of Urologic Robotic Surgery University of Maryland School of Medicine andstant Professor of Surgery - Urology Director of Urologic Robotic Surgery University of Maryland School of Medicine and Peter A. Pinto, M.D Head, Prostate Cancer Section Director, Fellowship Program Urologic Oncology Branch National Cancer Institute National Institutes of Health Bethesda, Maryland 20892-1210 Peter A. Pinto, M.D Head, Prostate Cancer Section  Director, Fellowship Program Urologic Oncology Branch National Cancer Institute  National Institutes of Health  Bethesda, Maryland Medical Research: What is the background for this study? What are the main findings? Response: For men suspected of having prostate cancer due to an elevated PSA or abnormal digital rectal exam, the next step in their diagnostic workup has traditionally been a standard 12-core biopsy to evenly sample the entire gland.  Unlike most other cancers, prostate cancer is one of the few solid tumors left which is diagnosed by randomly sampling the gland with the hope of biopsying the tumor, if it is present.  This paradigm has been largely due to the fact that imaging to date has been limited in its ability to identify prostate cancer.  Recent advancements in multiparametric MRI of the prostate however has significantly improved clinician's ability to identify regions in the prostate suspicious for cancer.  This has led to the emergence of MR/Ultrasound fusion technology which allows for targeted biopsy of the prostate into regions suspicious for cancer. Although conceptually, it makes sense that a targeted biopsy has the potential to perform better than the standard random sampling of the prostate in the diagnosis of prostate cancer, studies were needed to understand if this is true, and if so, if the improvement was substantial enough to justify the extra expense and effort needed to obtain a MRI guided biopsy.  This study performed at the National Cancer Institute's Clinical Center sought to address this clinical question of interest.  From 2007-2014, a total of 1003 men suspected to have prostate cancer underwent an MRI of the prostate.  If an area of suspicion was seen in the prostate, these men underwent both the targeted biopsy of the suspicious region in the prostate as well as the standard 12-core needle biopsy during the same session.  The results from the targeted biopsy were compared to the results of the standard biopsy. The key findings in this study was that targeted biopsy improved the rate at which high-risk clinically significant cancer was diagnosed by 30%.  Of interest, the study also found that low-risk, clinically insignificant disease (the type of prostate cancer that is unlikely to cause any harm to the patient over the course of his natural life) was decreased in diagnosis by 17%.  Decrease of diagnosis of such disease has the potential benefit that it could lead to less over-treatment of cancer that never needed to be treated.  In a subset of 170 men that ultimately underwent surgery to remove the prostate to treat their cancer, we were further able to examine how well the prostate biopsy reflected the actual cancer burden in the whole gland.   It is well known that standard biopsy can actually underestimate the total cancer grade in the whole prostate in upwards of 30-40% of cases.  We found that the targeted biopsy was significantly better at predicting whether the patient had intermediate to high-risk cancer compared to standard biopsy.  Through further analysis using a statistical method called decision curve analysis, we further found that for men who wish to undergo surgery for intermediate to high-risk cancer, but wish to go on active surveillance for low-risk cancer, targeted biopsy led to better decision making compared to standard biopsy, or even the two techniques combined. (more…)
Author Interviews, Breast Cancer, Brigham & Women's - Harvard, Cancer / 28.01.2015

Rachel A. Freedman MD, MPH Assistant Professor of Medicine, Harvard Medical School Department of Medical Oncology Dana-Farber Cancer Institute, Boston, MassachusettsMedicalResearch.com Interview with: Rachel A. Freedman MD, MPH Assistant Professor of Medicine, Harvard Medical School Department of Medical Oncology Dana-Farber Cancer Institute, Boston, Massachusetts Medical Research: What is the background for this study? What are the main findings? Dr. Freedman: Studies have previously looked at how general cancer knowledge may impact health conditions and rates of screening but none (to my knowledge) have focused on one’s knowledge about his/her own breast cancer. We surveyed 500 women who were diagnosed with early-stage breast cancer within the Northern California Cancer Registry and asked questions about their breast cancer subtype (I.e. Hormone receptor status and HER2 status), tumor grade, and stage. We then matched women’s answers to those collected by the registry to examine the correctness of the answers given. We found low overall rates of having knowledge about one’s disease and this was even more apparent for black and Hispanic patients. When education and health literacy were accounted for, disparities in knowledge remains for black women but were narrowed for Hispanic women in some cases. (more…)
Author Interviews, Breast Cancer, Karolinski Institute / 26.01.2015

Dr Jingmei Li Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm, SwedenMedicalResearch.com Interview with: Dr Jingmei Li Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm, Sweden Medical Research: What is the background for this study? What are the main findings? Response: Some cancers, such as interval breast cancers, which are detected within two years of a negative mammogram, are associated with more aggressive tumour characteristics and worse prognosis. As women with interval cancers were twice as likely to have a personal of family history of breast cancer, it is likely that there exist inherited variants that predispose a woman to the more aggressive form of the disease. Our study is one of the first to show empirical evidence that screen-detected and interval cancers are different genetically and are two distinct subtypes. (more…)
Author Interviews, Genetic Research, Melanoma, Nature / 25.01.2015

MedicalResearch.com Interview with: Prof Lukas Sommer. Ph.D. Cell and Developmental Biology University of Zurich Institute of Anatomy Zurich Switzerland MedicalResearch: What is the background for this study? What are the main findings? Prof. Lukas Sommer:   Melanoma, the most aggressive of all skin cancers, is often fatal for patients due to the pronounced formation of metastases. Up to date, a melanoma’s rampant growth was mainly attributed to genetic causes, such as mutations in certain genes. However, we now reveal that so-called epigenetic factors also play a crucial role in the formation of metastases in malignant skin cancer. Epigenetic factors do not influence the gene sequence directly, but rather cause certain genes and chromosomal segments to be packed in different densities – and thus make them accessible for reading. In our study we identified “EZH2” as an epigenetic control protein found very frequently in malignant melanoma cells compared to normal cells. In these cells, “EZH2” controls genes that govern both tumor growth and genes that are important for the formation of metastases. We exploited this central position of EZH2 to combat the cancer by using a pharmacological inhibitor to suppress the activity of EZH2. As a result, we were able to prevent the growth and malignant spread of the cancer in an animal model and in human melanoma cells. (more…)
Author Interviews, Breast Cancer, Scripps / 25.01.2015

Dr. Patrick Griffin PhD Professor and Chairman Department of Molecular Therapeutics Director of the Translational Research Institute Scripps Research Institute, Jupiter, FloridaMedicalResearch.com Interview with: Dr. Patrick Griffin PhD Professor and Chairman Department of Molecular Therapeutics Director of the Translational Research Institute Scripps Research Institute, Jupiter, Florida MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Griffin: We identified a novel synthetic compound known as SR1848 that sharply inhibits the activity and expression of “liver receptor homolog-1” or LRH-1, a protein that plays an important role in the progression of breast and pancreatic cancers. Our new study shows that SR1848 removes LRH1 from DNA, shutting down expression of LRH-1 target genes, and halts cell proliferation. It’s a novel compound that appears to be a promising chemical scaffold for fighting tumors that are non-responsive to standard therapies. (more…)
Author Interviews, Colon Cancer / 22.01.2015

Jason A. Zell, D.O., M.P.H. Program Director, Hematology/Oncology Fellowship Program Division of Hematology/Oncology Department of Medicine UC Irvine HealthMedicalResearch.com Interview with: Jason A. Zell, D.O., M.P.H. Program Director, Hematology/Oncology Fellowship Program Division of Hematology/Oncology Department of Medicine UC Irvine Health Medical Research: What is the background for this study? What are the main findings? Dr. Zell: Colorectal cancer incidence (CRC) has been declining in the U.S. since 1975, due largely to screening for premalignant polyps. Screening in the U.S. begins at age 50 for average risk individuals, and so the vast majority of Young Adults in the U.S. (defined as age 20-39 in our study) are unscreened. Recently, several studies have reported an increased risk of colorectal cancer among U.S. individuals under age 50. In our analysis of 231,544 CRC cases in California over a 22 year period, we identified 5617 cases among Young Adults (age 20-39). As expected, the overall risk of colorectal cancer in Young Adults is low. However, colorectal cancer is increasing among Young Adults as observed in this population-based study, and certain groups remain at particularly high risk. For example, Hispanic Females age 20-29 were observed to have nearly a 16% increase in colorectal cancer risk when comparing the Biannual Percent Change over the course of the study period.   Also concerning was the observation that Young Adults were more likely to be diagnosed with colorectal cancer at an advanced stage than adults in the “screened population” (ie, those age 50 and over). (more…)
Author Interviews, Coffee, JNCI, Melanoma, NIH, Yale / 21.01.2015

MedicalResearch.com Interview with: Erikka Loftfield Doctoral student at the Yale School of Public Health Fellow at the National Cancer Institute Medical Research: What is the background for this study? What are the main findings? Response: Previous studies have reported conflicting results on the association between coffee drinking and melanoma. We sought to clarify this relationship using data from the large NIH-AARP Diet and Health Study. We followed over 400,000 retirees aged 50 to 71 years at study entry for an average of 10 years. Participants were asked to report typical coffee intake. During the course of follow-up nearly 3,000 cases of malignant melanoma occurred. In our study, we observed that individuals who reported the highest total coffee intake (4 cups/day) had about 20% lower risk of malignant melanoma compared with those who did not consume coffee. (more…)
Author Interviews, Breast Cancer, Nutrition / 19.01.2015

Cecilia Cesa Schiavon Department of Nutrition, Federal University of Santa Catarina Florianópolis, Santa Catarina, BrazilMedicalResearch.com Interview with: Cecilia Cesa Schiavon Department of Nutrition, Federal University of Santa Catarina Florianópolis, Santa Catarina, Brazil Medical Research: What is the background for this study? What are the main findings? Response: The study was based on a nutritional intervention for patients undergoing treatment for breast cancer. The intervention took place right after the surgical procedure and lasted about a year, until the end of chemotherapy. The patients were submitted to a special methodology of intervention, aimed at increasing fruit and vegetable intake and reducing red and processed meat, following the World Cancer Research Fund and the American Institute for Cancer Research in the document entitled Food, Nutrition, Physical Activity and the prevention of Cancer: A Global Perspective”. The main findings show that women undergoing breast cancer treatment may benefit from immediate, individualized, and detailed nutrition monitoring through appropriate nutrition education. (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Science / 19.01.2015

Lee Zou, Ph.D. Professor of Pathology, Harvard Medical School The Jim & Ann Orr MGH Research Scholar Associate Scientific Director, MGH Cancer CenterMedicalResearch.com Interview with: Lee Zou, Ph.D. Professor of Pathology, Harvard Medical School The Jim & Ann Orr MGH Research Scholar Associate Scientific Director, MGH Cancer Center Medical Research: What is the background for this study? What are the main findings? Dr. Lee Zou: Cancer cells must rely on telomerase or the alternative lengthening of telomere (ALT) pathway to maintain telomeres and bypass replicative senescence. The ALT pathway is active in about 10-15% of human cancers, and it is particularly prevalent in specific cancer types, such as osteosarcoma, glioblastoma, and neuroendocrine pancreatic tumors. ALT is a recombination-mediated process. Whether the reliance of cancer cells on  alternative lengthening of telomere can be exploited therapeutically was not known. In our study, we discovered that the ATR kinase is a key regulator of alternative lengthening of telomere. We found that ATR inhibitors disrupt ALT effectively. Furthermore, we found that ATR inhibitors selectively kill ALT-positive cancer cells in a panel of caner cell lines. These findings have suggested the first rational therapeutic strategy for the treatment of ALT-positive cancer. (more…)
Author Interviews, Breast Cancer, Inflammation / 16.01.2015

Dr. Jorge Morales-Montor Departamento de Inmunología Instituto de Investigaciones Biomédicas Universidad Nacional Autónoma de México México City MéxicoMedicalResearch.com Interview with: Dr. Jorge Morales-Montor Departamento de Inmunología Instituto de Investigaciones Biomédicas Universidad Nacional Autónoma de México México City México MedicalResearch: What is the background for this study? Dr. Morales-Montor: Cytokines are highly inducible, secretory proteins that mediate intercellular communication in the immune system. They are grouped in several protein families referred as tumour necrosis factors, interleukins, interferons and colony stimulating factors. In recent years, it has become clear that some of these proteins as well as their receptors are produced in the organisms under physiological and pathological conditions. The exact initiation process of breast cancer is unknown, although several hypotheses have emerged. Inflammation has been proposed as an important player in tumor initiation, promotion, angiogenesis and metastasis, all phenomena in which cytokines are prominent players. The data we have hitherto let us suggest that cytokines play an important role in the regulation of both induction and protection in breast cancer. This knowledge could be fundamental for the proposal of new therapeutic approaches to particularly breast cancer and other cancer related disorders. (more…)
Author Interviews, Prostate, Prostate Cancer, Urology / 16.01.2015

MedicalResearch.com Interview with: Mufaddal Mamawala, MBBS, MPH, CPH Biostatistician Johns Hopkins School of Medicine Brady Urological Institute Medical Research: What is the background for this study? What are the main findings? Dr. Mamawala: Twenty years after prostate-specific antigen (PSA) was FDA approved for the diagnosis of prostate cancer, its use remains highly controversial. There has been an ‘over- diagnosis’ and ‘over-treatment’ of low-risk prostate cancers that would have never progressed to a more lethal form of the disease during one’s life. Active surveillance (AS) is an alternative to immediate treatment, which allows for monitoring of favorable risk patients with selective delayed intervention among those with disease progression. However  ‘misclassification’ is a cause of concern for patients in the initial years of been in AS. The initial biopsy may have missed an area of prostate with an aggressive cancer, due to under-sampling of cores or due to randomness, such that this patient could get misclassified as having a low-risk disease and by the time the follow-up biopsy shows an aggressive cancer the window of curability is lost. However with more sampling of the prostate there is more likelihood to find an aggressive cancer. As such if the patient is compliant with their biopsies, and more prostate is sampled under the microscope, better are the chances of finding a higher risk cancer. Conversely if the patient has more biopsies that show no high-risk cancer then they are less likely to have a high-risk cancer on future biopsies. Thus we wanted to evaluate the risk of reclassification, from a low-risk disease to a high-risk disease (higher Gleason score, or increase in extent of the disease), over a period of time in compliant active surveillance patients.  The length of time under Active surveillance without reclassification has not been evaluated as a predictor of future reclassification. Biopsies are invasive procedures, and the fact that patient has to undergo this invasive procedure regularly is a deterrent from been in Active surveillance. This study would help to make informed decisions about the need for doing frequent biopsies in light with other clinical factors especially in older patients who had many non-reclassifying biopsies before. We found that the risk of reclassification was not equally distributed across time. As a result of ‘under sampling’ of prostate at diagnostic biopsy we had highest rates of reclassification in the first two years of been in Active surveillance with more than 50% of total reclassifications happening during those two years. The ‘low-risk’ and the ‘very-low-risk’ groups, determined by the Epstein criteria, had similar rates of reclassification in the first two years. After first two years the ‘low-risk’ group were 2.4 times as likely to have a higher risk of reclassification than the ‘very-low-risk’ group. In both the groups the risk of reclassification declined over time significantly by at least 30% with each biopsy that did not show reclassification. (more…)
Author Interviews, Melanoma / 14.01.2015

Keiran Smalley, PhD. Scientific Director, The Comprehensive Melanoma Research Center Associate Professor The Moffitt Cancer Center & Research Institute, Tampa, FLMedicalResearch.com Interview with: Keiran Smalley, PhD. Scientific Director, The Comprehensive Melanoma Research Center Associate Professor The Moffitt Cancer Center & Research Institute, Tampa, FL   Medical Research: What is the background for this study? What are the main findings? Dr. Smalley: Although many patients with BRAF mutant melanoma respond very well to BRAF inhibitors and the BRAF/MEK inhibitor combination, resistance is commonplace and the majority of those treated ultimately fail therapy. Most studies to date have focused upon the genetic changes that are associated with acquired BRAF and BRAF/MEK inhibitor resistance. We decided to take a different approach and to use proteomics to comprehensively map all of the signaling changes associated with resistance. Our study showed that melanoma cells with resistance to BRAF and BRAF/MEK inhibition were highly invasive and aggressive. This aggressive phenotype was driven through a cell surface receptor called EphA2, and this became upregulated in both melanoma cell cultures and in patient tumors following BRAF inhibitor treatment. As this suggested that the resistant cells would be more metastatic, we then performed animal experiments and analyzed tumors from melanoma patients receiving BRAF inhibitor. These studies showed an increase in EphA2 expression in the metastatic tumors that was lacking in the primary tumors. When we looked at cohorts of melanoma patients who received either a BRAF inhibitor or an older chemotherapy drug, we found that more of the BRAF inhibitor treated patients seemed to develop disease at new sites. Together this suggested that BRAF inhibition may switch the cancer cells to being more metastatic. (more…)
Author Interviews, Breast Cancer, JAMA / 14.01.2015

Javaid Iqbal, MD, MSC (Candidate) Institute of Medical Sciences, and Women’s College Research Institute/Women’s College Hospital University of Toronto, Toronto CanadaMedicalResearch.com Interview with: Javaid Iqbal, MD, MSC (Candidate) Institute of Medical Sciences, and Women’s College Research Institute/Women’s College Hospital University of Toronto, Toronto Canada What is the background for this study? What are the main findings? Dr. Iqbal: A woman’s racial/ethnic background predicts her participation in breast cancer control program (i.e., awareness and screening). The ultimate objective of breast cancer control program is to detect cancer at an optimal stage, which is stage I, because women with stage I breast cancer survive longer. Given the racial/ethnic diversity of North America, this poses questions such as “what predicts stage I breast cancer in the multiethnic North American population?”, “what predicts its survival?”, and “does a woman’s ethnic background plays a role in predicting an early stage, and survival?” We studied 373,563 women diagnosed with invasive breast cancer in the United States between 2004 and 2011. We followed these women for 7 years and recorded whether or not they died of breast cancer, or whether they are still alive. We then divided all women into different ethnic groups, in particular white, black, Chinese, Japanese, and Indian/Pakistani (South Asian). For each racial/ethnic group, we estimated proportions of women who were diagnosed with stage I breast cancer, and risk of death at 7 years. Our aim was to determine if the racial/ethnic differences in early stage breast cancer, and its survival were better explained by intrinsic biological differences in tumor characteristics, or by differences in early-detection of breast cancer. We found that a woman’s racial/ethnic background predicted the diagnosis of stage I breast cancer, as well as her risk of dying at 7 years after breast cancer. A black woman was less likely than a white woman to be diagnosed with stage I breast cancer. A black woman was also more likely than a white woman to die of stage I breast cancer 7 years after her diagnosis. The Japanese and Chinese women were more likely than white women to be diagnosed with stage I breast cancer. The risk of death at 7 years was lowest for Indian or Pakistani (South Asian) women. Furthermore, even for small sized (2.0) breast cancers the risk of death at 7 years was higher for black women (9%), compared to white women (5%). Compared to white women, small sized breast cancers in black women were more aggressive at diagnosis, and had spread to lymph nodes and other organs. (more…)