Allergies, Author Interviews, Genetic Research, Hepatitis - Liver Disease / 08.09.2020 Interview with: Takanori Takebe MD Director for Commercial Innovation, Center for Stem Cell and Organoid Research and Medicine (CuSTOM) Assistant Professor, University Cincinnati Department of Pediatrics, Cincinnati Children’s Professor, Institute of Research Tokyo Medical and Dental University, Japan What is the background for this study?  What are the main findings? Response: Drug induced liver injury (DILI) is rare yet highly unpredictable disorder that oftentimes causes drug failure withdrawn from the market during clinical trial even at a very rare incidence of DILI (1/10,000). Indeed, one particular drug TAK875 (Fasigliam) was the case despite promising efficacy. This not only disappoints patient but impact significant financial risk to pharmaceuticals. In collaboration with DILI genomics consortium at US, EU and UK, we’ve found +20,000 genetic make up (variants) defines potential risk of developing Drug induced liver injury thru amplifying cellular stress signal cascades that were investigated by human cell, organoid and patient datasets. (more…)
Author Interviews, Cost of Health Care, Genetic Research, Immunotherapy, Melanoma, Surgical Research / 03.09.2020 Interview with: Edmund K Bartlett, M.D. Department of Surgery/Division of Surgical Oncology Memorial Sloan Kettering Cancer Center New York, New York What is the background for this study? Response: Indications for adjuvant therapy for resected, high-risk melanoma is a controversial and rapidly-evolving topic in melanoma treatment. Immunotherapy treatments targeting PD-1 have significantly improved survival in advanced-stage disease, but the magnitude of survival benefit in stage III disease--particularly stage IIIA--remains unclear. Recently, 31-GEP (a gene expression profiling assay) has been studied as a risk-stratifying tool to identify patients who are at higher risk for systemic recurrence. Ideally such a tool could identify patients most likely to benefit from immunotherapy treatment in the adjuvant setting (when all visible disease has been removed). (more…)
Author Interviews, Biomarkers, Cancer Research / 20.08.2020 Interview with: Dr. Alexey Aleshin, M.D., MBA Senior Medical Director Natera What is the background for this study? Response: Checkpoint inhibitor-based immunotherapies (ICI)  have changed the management of a range of cancers of diverse histologies. While these therapies are well tolerated and efficacious, only a minority (<20%) of patients respond to treatment or derive durable clinical benefit from them, highlighting the need for a pan-cancer biomarker that can predict response prior to, or shortly after, treatment initiation. With immune checkpoint inhibitors (ICIs) rapidly becoming a cornerstone of cancer therapy, early determination of response to ICI treatment can optimize patient benefit and minimize the risk of toxicities, while potentially reducing unnecessary treatment and costs to patients and payers. Additionally, due to the nature of immune checkpoint inhibition, atypical patterns of response have emerged. For instance, tumor pseudoprogression — a transient increase in tumor size due to the infiltration of immune cells, followed by delayed shrinkage — has been reported in as much as 10% of patients receiving ICI therapy. Distinguishing pseudoprogression from true progression is clinically important to avoid premature discontinuation of a treatment that may have future benefit, or delay the initiation of an alternative line of therapy. However, they are hard to differentiate using current imaging techniques. Our study published in Nature Cancer earlier this month, demonstrates that bespoke circulating tumor DNA (ctDNA) testing may be a valuable tool that sheds light on both of these issues. (more…)
Author Interviews, Neurological Disorders, Personalized Medicine / 19.06.2020 Interview with: Hänggi, PhD Chief Scientific Officer Polyneuron Pharmaceuticals What is the background for this study? Response: Anti-MAG neuropathy is a rare form of acquired demyelinating neuropathy. The disease onset normally presents after the age of 50 years and is 2.7 times more frequent in men than in women, with a prevalence of about 1 in 100,000. It is caused by the production of monoclonal anti-MAG IgM antibodies that recognize the HNK-1 epitope. The myelin-associated glycoprotein MAG is a mediator for the formation and maintenance of the myelin sheaths. There is strong evidence that the binding and deposition of anti-MAG IgM autoantibodies on myelin sheath is responsible for the demyelination, which clinically manifests itself as a peripheral neuropathy affecting primarily sensory nerves. However, the causes and the exact mechanisms behind the expansion of anti-MAG IgM producing B-cell and plasma cell clones are not fully understood. Most off-label treatments aim to reduce pathogenic autoantibody titers by depleting  autoantibody-producing B cell clones which interfere with antibody-effector mechanisms, or physically remove autoantibodies from the circulation. Most frequently, the anti-CD20 monoclonal antibody rituximab is used to treat anti-MAG neuropathy patients. However, all of these treatment options often lack of selectivity, efficiency, or can induce severe adverse effects in some patients. Polyneuron has designed PN-1007 to highly selectively target the IgM autoantibodies that cause anti-MAG neuropathy. PN-1007 is a glycopolymer that mimics the natural HNK-1 carbohydrate epitope found on myelin of peripheral nerves and binds to the circulating disease-causing antibodies. By eliminating these pathogenic antibodies, PN-1007 may protect the integrity of the neuronal myelin sheaths of anti-MAG neuropathy patients. (more…)
AACR, Author Interviews, Boehringer Ingelheim, Cancer Research / 13.05.2020 Interview with: Dr. Udai Banerji, MD The Institute of Cancer Research and The Royal Marsden What is the background for this study? Response: Not only have I been working in the RAS mutations oncology world for a while, but I also have prior preclinical experience working with VS-6766 (RAF/MEK inhibitor) and defactinib (FAK inhibitor), the two drugs in the Phase 1 study that was presented at the American Association for Cancer Research (AACR) annual medical meeting on April 27th. It is important to know that there is a great significant medical need for novel treatments for KRAS mutant tumors, which are difficult to treat, aggressive, and quite common across advanced solid tumors, including low-grade serous ovarian cancer (LGSOC), non-small cell lung cancer (NSCLC) and colorectal cancer (CRC), resulting in the need for novel treatments in an area of significant medical need. I felt that early signals in preclinical research warranted a clinical trial; so that, combined with my RAS experience, made pursuing the Phase 1 study a clear fit. A clinical trial setting allowed us to explore RAF and RAS inhibitor combinations in multiple tumor trials, which was our aim. The data presented at AACR convey safety and dose response results from the dose-escalation portion and expansion cohorts from an open-label, investigator-initiated Phase 1 study evaluating the combination of VS-6766 (RAF/MEK inhibitor) and defactinib (FAK inhibitor) therapy in patients with LGSOC and KRAS mutant NSCLC. The introductory data described in the study suggest that a novel intermittent dosing schedule of RAF/MEK and FAK inhibitor combination therapy has promising clinical activity in patients with KRAS mutant LGSOC and KRASG12V mutant NSCLC, including patients formerly treated with a MEK inhibitor. Expansion cohorts remain ongoing.  (more…)
Author Interviews / 11.05.2020 Interview with: David Spetzler, M.S., Ph.D., M.B.A. President and Chief Scientific Officer Caris Life Sciences What is the background for this announcement (WES)? Response: The announcement is about the launch of Caris’ latest molecular profiling test, called MI ExomeTM.  MI Exome a next-generation sequencing-based assay analyzing the whole exome of 22,000 DNA genes.  It is unique in that it will be run on every patient and will deliver unprecedented detail into the genomic characteristics of cancers, which will greatly improve our ability to understand cancer and provide insights needed to help physicians and patients make more informed treatment decisions that improve outcomes. (more…)
Author Interviews, Cancer Research, Genetic Research, Melanoma / 29.04.2020 Interview with: Dr. Matthew H. Law, PhD Senior Research Officer, Statistical Genetics QIMR Berghofer What is the background for this study? Response: A large genetic study of melanoma involving a global collaboration of scientists, co-led by QIMR Berghofer, the University of Leeds in the UK, and the National Cancer Institute in the US which is part of the National Institutes of Health, has been published in the prestigious journal Nature Genetics. Melanoma is a sometimes-deadly skin cancer, with an estimated 350,000 cases worldwide in 2015, resulting in nearly 60,000 deaths. Melanoma begins in melanocytes, cells in the skin responsible for making the pigment melanin that gives colour to the skin. Melanin is able to block some of the harmful effects of UV radiation, which is why people with pale skin are at a higher risk of skin cancer, but the protection is not complete. Moles also develop from melanocytes, and having a high number of moles is a risk factor for melanoma. UK based co-lead author, Dr Mark Iles from the University of Leeds’s Institute for Data Analytics, said the researchers examined DNA from 37,000 people who had been diagnosed with melanoma and compared their genetic information to that of nearly 400,000 people with no history of the disease.” Joint study leader and QIMR Berghofer statistical geneticist Associate Professor Matthew Law said the researchers identified 33 new regions of the genome and confirmed another 21 previously reported regions that are linked to a person’s risk of developing melanoma of the skin. Two of the new regions we’ve discovered that are linked to melanoma have previously been linked to autoimmune disorders. This provides further evidence that the immune system plays an important role in a person developing melanoma. We also found an association between melanoma and common genetic variants in the gene TP53, which is a gene critical in controlling DNA repair when cells divide, and in suppressing cancer.” Co-lead author on the study and senior investigator at the National Cancer Institute, Dr Maria Teresa Landi, said the research also uncovered other important clues to the genetic causes of melanoma. We used the relationship between moles, pigmentation, and melanoma to identify 31 additional gene regions that potentially influence melanoma risk. For example, one of the regions we identified is involved in melanocyte growth,” Dr Landi said. “Moreover, we also included people from Mediterranean populations involved in the MelaNostrum Consortium. Most studies of melanoma use people with northern or western European ancestry (e.g. British) and by expanding our analysis to include Mediterranean populations, we will gain a greater understanding of the genetics of melanoma in this highly sun exposed group.” (more…)
Author Interviews, Diabetes, Genetic Research, Personalized Medicine / 27.04.2020 Interview with: Fumihiko Urano, MD, PhD Samuel E. Schechter Professor of Medicine Division of Endocrinology, Metabolism, and Lipid Research Washington University School of Medicine What is the background for this study? Response: Wolfram syndrome is a rare monogenic disease characterized by insulin-dependent diabetes, retinal degeneration, and neurodegeneration. Using gene editing by CRISPR-Cas9, in combination with patient-derived induced pluripotent stem cells (iPSCs), we were able to make normal insulin-producing pancreatic beta cells by correcting Wolfram Syndrome gene mutation. We could cure diabetes in cells and mice. Because we can create any types of tissues from iPSCs, our next step would be to replicate this success for other medical problems, including retinal regeneration and neurodegeneration. (more…)
Author Interviews, Breast Cancer, JAMA, Mammograms / 15.11.2019 Interview with: Dr. Elham Kharazmi, MD, PhD Co-Leader, Risk Adapted Prevention (RAD) Group Division of Preventive Oncology National Center for Tumor Diseases (NCT) German Cancer Research Center (DKFZ) Germany What is the background for this study? Response: Breast cancer is the most common cancer in women worldwide and the second leading cause of cancer death in American women, exceeded only by lung cancer. Available evidence suggests that implementation of a screening program can decrease breast cancer mortality. Reductions in breast cancer mortality in Europe over the past two decades have been associated at least in part with the implementation of screening programs. Screening enables the detection of tumors at an early stage, when more treatment options are feasible and most effective. However, screening is associated with substantial risks, such as over-diagnosis, false-positive results, and physical and psychological harms, particularly when large numbers of women with low risk are frequently screened. (more…)
Author Interviews, Cost of Health Care, Genetic Research, Personalized Medicine / 02.07.2019

Dr. Winegarden
Dr. Winegarden Interview with:

Wayne Winegarden, Ph.D.
Director, Center for Medical Economics and Innovation
Pacific Research Institute  What is the background for this poll? Would you tell us a little about the Center for Medical Economics and Innovation? 

Response: Recent press reports have focused on how extensive innovative gene therapies can be.  PRI was interested in learning where Americans stand on these cures of the future, and commission a new national opinion survey to find out.

The Center for Medical Economics and Innovation is a new center launched by PRI this spring to research and advance policies showing how a thriving biomedical and pharmaceutical sector benefits both patients and economic growth. Medical innovation is an important driver of economic growth, responsible for over $1.3 trillion in economic activity each year. As the Milken Institute has found, every job in the biomedical sphere supports another 3.3 jobs elsewhere in the economy.

Among the activities of the Center – which can be accessed at – are providing free-market analysis to evaluate current policy proposals, producing easy-to-understand data and analysis on current trends in medical science, breaking down complex issues like pharmaceutical and biomedical pricing structures, and demonstrating the benefits that market-based reforms can offer patients and the U.S. health care system.  (more…)

Author Interviews, Inflammation, Kidney Disease, Personalized Medicine / 31.07.2018 Interview with: Michael P. Madaio, MD Sydenstricker Professor and Chairman Department of Medicine Medical College of Georgia at Augusta University What is the background for this study? Response: Glomerulonephritis is a inflammatory disease of the kidney.  Glomeruli are the filtering units in the kidney. This is most often immunologically mediated and are autoimmune. Most therapies are directed at inhibiting the Immune/autoimmune process (immunotherapy) systemically. (more…)
Author Interviews, Diabetes, Heart Disease, JAMA, Personalized Medicine / 21.11.2017 Interview with: Dr. MalikDr. Shaista Malik MD PhD MPH Director of Samueli Center For Integrative Medicine Assistant Professor, School of Medicine University of California, Irvine What is the background for this study? What are the main findings? Response: Having diabetes has been considered to be a risk equivalent to already had a myocardial infarction for predicting future cardiovascular events.  We were interested in testing whether further risk stratification in those with diabetes and metabolic syndrome, using coronary artery calcium (CAC), would result in improved prediction of cardiovascular events. We found that CAC score was associated with incident coronary heart disease and cardiovascular disease more than a decade after the scoring was performed.  We also found that even after we controlled for the duration of diabetes (of 10 years or more), insulin use, or hemoglobin A1c level, coronary artery calcium remained a predictor of cardiovascular events. (more…)
Author Interviews, Biomarkers, Genetic Research, Personalized Medicine / 15.05.2017 Interview with: 3D SignaturesJason Flowerday, CEO Director of 3D Signatures What is the background for 3D Signatures? Response: 3D Signatures, and its clinical lab tests, which incorporate its proprietary TeloViewTM software analytics, is the culmination of over 20 years of ground-breaking research conducted by Dr. Sabine Mai and her colleagues. It is the only technology in the world that quantifies genomic instability, which is the hallmark of cancer and other proliferative diseases at the whole-cell level. By measuring the degree of genomic instability from different tissues, TeloViewTM has produced clinically actionable distinctions in the stage of disease, rate of progression of disease, drug efficacy, and drug toxicity. The technology is well developed and supported by 22 clinical studies on over 2,000 patients on 13 different cancers including Alzheimer’s disease. The results have been exceptional and represent a universal biomarker platform across all disease areas that the company has investigated to date. (more…)
Author Interviews, Diabetes, NEJM, Ophthalmology, Personalized Medicine / 20.04.2017 Interview with: John M. Lachin, Sc.D. Research Professor of Biostatistics and of Epidemiology, and of Statistics The George Washington University Biostatistics Center and David Matthew Nathan, M.D. Professor of Medicine, Diabetes Unit Massachusetts General Hospital What is the background for this study? Response: Traditional guidelines for screening for retinopathy, based on indirect evidence, call for annual examinations. The automatic annual screening for retinopathy, without considering potential risk factors for progression,  appears excessive based on the slow rate of progression through sub-clinical states of retinopathy. (more…)
Author Interviews, Biomarkers, Breast Cancer, Genetic Research, Race/Ethnic Diversity, Wistar / 28.02.2017 Interview with: Maureen E. Murphy, Ph.D. Professor and Program Leader, Molecular and Cellular Oncogenesis Program Associate Vice President for Faculty Affairs Associate Director for Education and Career Development The Wistar Institute Philadelphia, PA 19104 What is the background for this study? What are the main findings? Response: The Murphy group discovered a coding-region variant of the p53 tumor suppressor gene, called Pro47Ser, that exists in individuals of African descent. In previous studies this group reported that this amino acid change reduces the ability of p53 to function as a tumor suppressor. In this study, African American women from two different large cohorts were assessed for the incidence of the Pro47Ser variant in pre-menopausal breast cancer. A modest but statistically significant association was found between Pro47Ser and pre-menopausal breast cancer. (more…)
Author Interviews, Breast Cancer, Chemotherapy, Personalized Medicine / 24.02.2017 Interview with: Eran Andrechek, PhD Eran Andrechek, PhD Associate Professor Department of Physiology Michigan State University East Lansing, MI Associate Professor Department of Physiology Michigan State University East Lansing, MI What is the background for this study? Response: Of the various types of breast cancer, triple negative breast cancer (lacking estrogen receptor, progesterone receptor and HER2) has the worst outcome and is largely limited to chemotherapy for treatment.  Other types can be treated with personalized medicine, resulting in better outcome.  For instance, a HER2+ve breast cancer can be treated with Herceptin, which targets HER2 itself.  The fact that triple negative breast cancer lacks these sort of targeted treatments presents a clear need in breast cancer therapy. The goal of this study was to bring together our computational work using large databases from breast cancer with research into therapeutic options.  Essentially we wanted to ask if we could use patterns in what genes were being expressed to predict optimal therapy for triple negative breast cancer.  (more…)
Author Interviews, Biomarkers, Genetic Research, Leukemia, Personalized Medicine / 05.08.2016 Interview with: Dr Laura Eadie PhD Post Doctoral Researcher Affiliate Lecturer Discipline of Medicine University of Adelaide Summary: Researchers based at SAHMRI (South Australian Health and Medical Research Institute) in Adelaide, South Australia have recently demonstrated the significance of early increases in the expression of ABCB1 in predicting long-term response to imatinib therapy. Lead researcher, Dr Laura Eadie, has recently had these findings published in the journal Leukemia and says that she hopes “the evidence provided by the study could be used to inform better patient treatment in the future”. What is the background for this study? What are the main findings? Response: ABCB1 (p-glycoprotein) is a membrane transporter known to be involved in the efflux of the tyrosine kinase inhibitors (TKIs) that are used to treat chronic myeloid leukaemia (CML). Overexpression of ABCB1 has also been demonstrated to cause resistance to the TKIs imatinib, nilotinib and dasatinib in vitro. Although studied previously in CML patients, the predictive value of ABCB1 in determining a patient’s long-term response to imatinib had not been realized ... until now. Previous studies investigating ABCB1 as a predictive biomarker focused on expression levels of ABCB1 at one time point in isolation. For our study, we have measured the levels of ABCB1 at two separate time points specified in the TIDEL II trial protocol: day 1 (prior to the start of imatinib therapy) and day 22 (three weeks on imatinib). We then calculated the fold rise in ABCB1 expression levels at day 22 compared with day 1 and grouped patients about the median into high and low fold rise. When we compared molecular outcomes for patients within these two ABCB1 expression groups we noticed a striking difference in outcome to imatinib therapy. (more…)
AACR, Author Interviews, Biomarkers, Cancer Research, Personalized Medicine, Stanford / 01.05.2016 Interview with: Dr. Elodie Sollier Chief Scientific Officer at Vortex Biosciences What is the background for this study? What are the main findings? Response: Circulating Tumor Cell (CTC) burden may be a useful biomarker of response to targeted therapy in PDX (Patient Derived Xenograft) mouse models. Vortex Biosciences’ technology has been proven to enrich CTCs from human blood, but use of the technology with mouse blood had not yet been explored. In this poster, human CTCs are isolated with both high efficiency and purity from xenograft model of breast cancer using Vortex’s technology. Circulating Tumor Cell enumeration increased as the tumor burden increased in the mouse demonstrating its utility as a biomarker for drug treatment response. (more…)
Author Interviews, Personalized Medicine, Pharmacology / 16.11.2015 Interview with: Diane Frenier Esq Reed Smith Corporate Partner Member of Corporate & Securities Group and Life Sciences Health Industry Group Background: Diane Frenier Esq discusses the M&A boom in the pharmaceutical and retail drug industry including a the "global study of 100 senior executives at life sciences companies by global law firm Reed Smith, in partnership with Mergermarket, reveals that 94% are planning to make an acquisition in the next year”. Medical Research: What are the main drivers behind the pursuit of cross-border life sciences deals? Ms Frenier: I think companies are trying to strengthen their capabilities in areas that are a core focus for them (e.g., in certain therapeutic areas, or for orphan drugs), and that includes adding products in those core focus areas and, in some cases, broadening geographically so they can market products in those core focus areas on a more global basis.  This will allow them to use their resources more efficiently and take advantage of saving from reducing redundancies. (more…)
AACR, Author Interviews, Genetic Research, Melanoma, NYU, Personalized Medicine, Wistar / 21.04.2015

Melissa Wilson, MD, PhD Assisstant Professor Perlmutter Cancer Center NYU Langone Medical Center New York, Interview with: Melissa Wilson, MD, PhD Assisstant Professor Perlmutter Cancer Center NYU Langone Medical Center New York, NY Medical Research: What is the background for this study? What are the main findings? Dr. Wilson: Metastatic cutaneous melanoma is an extremely aggressive form of skin cancer.  Traditionally, it has been characterized by clinicopathologic characteristics.  More recently, melanoma tumors have also been stratified by common somatic mutations for which targeted therapies have been developed or are under investigation, including BRAF, NRAS and KIT.  In addition to somatic mutations, aberrant intracellular signaling pathways and cell cycle disruption contribute to melanoma pathogenesis.  Indeed, recent next generation sequencing studies have identified a number of new genes involved in melanomagenesis.  A comprehensive evaluation and understanding of concurrent and mutually exclusive mutations in tumors has been lacking.  Therefore, we developed a comprehensive custom targeted capture of 108 genes previously implicated in melanoma pathogenesis.  We used the targeted panel to perform massively parallel sequencing on 94 well-established human melanoma cell lines, 67 patient-derived xenografts (PDX), and 5 cell lines made from PDX, all untreated. Samples were clustered based on deleterious mutations.  Eighty-three percent of samples had deleterious mutations in the MAPK signaling pathway (including BRAF, RAS) and NF1.  Ten percent of samples had PI3K pathway mutations which were predominantly associated with BRAF mutations.  TP53 was found to be mutated in 24% of the samples and were also associated with mutations in the MAPK pathway.  Mutations in chromatin remodeling genes were mutually exclusive with each other, but were associated with BRAF and NRAS mutations.  Of particular interest, five of the 10 NF1mutated samples harbored likely deleterious mutations in MAP3K5 or MAP3K9, suggesting the potential involvement of JNK signal transduction pathway in a cohort of samples. (more…)
Author Interviews, Genetic Research, Nature, Pancreatic, UT Southwestern / 10.04.2015

Dr. Agnieszka Witkiewicz MD Associate Professor of Pathology Harold C. Simmons Comprehensive Cancer Center UT Interview with: Dr. Agnieszka Witkiewicz MD Associate Professor of Pathology Harold C. Simmons Comprehensive Cancer Center UT Southwestern MedicalResearch: What is the background for this study? Dr. Witkiewicz: Pancreatic ductal adenocarcinoma (PDA) has a dismal prognosis, with a five year survival rate of approximately 6%. This poor outcome is related to multiple factors, including the relatively late stage of diagnosis, many patients presenting with unresectable disease, and therapy recalcitrance resulting in disease recurrence in spite of operable disease and systemic therapy. Thus far, insights into how to target the treatment of Pancreatic ductal adenocarcinoma have remained unclear in spite of prior sequencing efforts. MedicalResearch: What are the main findings? Dr. Witkiewicz: The underlying critical finding of the study was that Pancreatic ductal adenocarcinoma is genetically diverse and that, in principle, this diversity could be exploited for the treatment of disease.   Specifically, many cases harbored deregulation in pathways that are the target for drug development.   For example, we identified cases that were driven by BRAF V600E and that were sensitive to the FDA approved drug Vemurafenib.   Similarly, multiple cases harbored defects in DNA repair processes that impart sensitivity to select chemotherapeutic agents and PARP inhibitors.  Common pathway deregulation was observed in reference to beta-catenin, notch, hedgehog, chromatin remodeling, and cell cycle regulatory pathways that are all targets for therapeutic intervention. (more…)
Author Interviews, Duke, Personalized Medicine, Technology / 27.03.2015

Ryan Jeffrey Shaw, PhD, MS, RN Assistant Professor School of Nursing Center for Health Informatics Center for Precision Medicine Duke University Interview with: Ryan Jeffrey Shaw, PhD, MS, RN Assistant Professor School of Nursing Center for Health Informatics Center for Precision Medicine Duke University Medical Research: What is the background for this study? What are the main findings? Dr. Shaw: Primary care delivery revolves around a series of episodes, rather than functioning as a continuum. When patients come to a clinic data on their health is collected as a single data point. This model neglects potentially meaningful data from patients’ daily lives and results in less informed treatment and scheduling of follow-up visits. Lack of meaningful data further blinds clinicians to patients’ health outside of the clinic and can contribute to unnecessary emergency department visits and hospitalizations. Personalized care through mobile health technologies inspires the transition from isolated snapshots based on serial visits to real time and trended data. By using technologies from cell phones to wearable sensors, providers have the ability to monitor patients and families outside of the traditional office visit. (more…)
Author Interviews, Colon Cancer, Genetic Research, JAMA / 12.03.2015

Matthew B. Yurgelun, MD Instructor in Medicine Harvard Medical Interview with: Matthew B. Yurgelun, MD Instructor in Medicine Harvard Medical School Medical Research: What is the background for this study? What are the main findings? Dr. Yurgelun: Germline mutations in the TP53 gene are linked to Li-Fraumeni syndrome, which is an inherited syndrome associated with a 73-100% lifetime risk of cancer. Classically, cancers linked to Li-Fraumeni syndrome include early-onset breast cancer, leukemias, soft tissue sarcomas, brain cancer, and adrenocortical cancer, although recent data have shown an increased risk of colorectal cancer as well.  Our study’s primary aim was to determine the frequency of germline TP53 mutations in patients with early-onset colorectal cancer. We studied 457 patients from the multinational Colon Cancer Family Registry who were diagnosed with colorectal cancer at age 40 or younger, and found that 1.3% carried a germline alteration in the TP53 gene.  None of these individuals had personal or family histories of cancer that fulfilled clinical criteria for Li-Fraumeni syndrome. (more…)
Author Interviews, Genetic Research, Melanoma, Personalized Medicine / 08.03.2015

Pedram Gerami MD Associate Professor of Dermatology and Pathology Northwestern Interview with: Pedram Gerami MD Associate Professor of Dermatology and Pathology Northwestern University MedicalResearch: What is the background for this study? What are the main findings? Dr. Gerami: The outcomes for patients with cutaneous melanoma are highly variable and there are limitations to the conventional staging system for melanoma. For example while the status of the sentinel lymph node biopsy is considered the strongest prognosticator, approximately 2/3 of cutaneous melanoma patients that ultimately die from their melanoma will have a negative sentinel lymph node biopsy result. In this study we showed that using a technique known as mRNA expression profiling to determine which genes are highly active and which are not that a molecular prognostic assay with accuracy could be developed. This assay can accurately classify patients based on their gene signature as having a high or low risk for metastasis and death from their melanoma. In an independent validation cohort, patients with a class I or low risk signature had a 5 year disease free survival rate of 97% while those with a class II or high risk signature had a 5 year disease free survival rate of only 31%. (more…)
Author Interviews, Breast Cancer, Duke, Genetic Research, JAMA, Personalized Medicine / 05.03.2015

Dr. Michaela A. Dinan Ph.D Department of Medicine Duke Interview with: Dr. Michaela A. Dinan Ph.D Department of Medicine Duke University Medical Research: What is the background for this study? What are the main findings? Dr. Dinan: We wanted to examine how  Oncotype DX® Breast Cancer Test (ODX) was being used in real-world practice at the population level. ODX has been examined in clinical trials and limited academic settings but we know that these patients are often younger, have fewer medical comorbidities, and do not necessarily accurately reflect the majority patients with cancer.  In our study, we observed that Oncotype DX® Breast Cancer Test was being used predominately in accordance with guidelines which recommend the test for women with estrogen-receptor positive, disease. We also looked just at women under the age of 70 who met guideline criteria for testing, because this population would include those women who were more likely to be chemotherapy candidates, and we saw a rapid uptake of the test between 2005 and 2009, with use of the test increasing from 8% to 39%. (more…)
Author Interviews, Cancer Research, MD Anderson, Nature, Personalized Medicine / 28.02.2015

Dr. Anil Sood MD Professor of Gynecologic Oncology and Reproductive Medicine The University of Texas MD Anderson Cancer Interview with: Dr. Anil Sood MD Professor of Gynecologic Oncology and Reproductive Medicine The University of Texas MD Anderson Cancer Center Medical Research: What is the background for this study? What are the main findings? MedicalResearch: What is the background for this approach? What are the main findings? Dr. Sood: The background involves several different issues: management approaches have varied quite a bit across the US; definition of “optimal” surgery and rates of complete surgical removal of tumor (R0) have also varied. It is quite apparent that patients who benefit the most from surgery upfront are those who have removal of tumor resection. To address these issues, we have implanted a much more personalized approach whereby patients with suspected advanced ovarian cancer undergo laparoscopic assessment using a validated scoring system (based on the pattern and extent of disease noted during laparoscopic assessment); patients with a score <8 undergo upfront debulking surgery and those with a score ≥8 receive neoadjuvant chemotherapy followed by surgery after 3-4 cycles. To date, this program has been fully implemented as part of the Moonshot Program at M.D. Anderson. This program has already resulted in several benefits – for example, prior to this algorithm being put into place among all patients with suspected advanced ovarian cancer, around 20% would have removal of tumor resection; after the implementation of the algorithm, of those going to upfront debulking surgery (after laparoscopic assessment), almost 85% of times removal of tumor resection can be achieved. Also, this method of treatment is allowing for new and innovative clinical trial designs. (more…)
Author Interviews, Genetic Research, UCSD / 18.02.2015

Dr. Rahul S. Desikan MD, PhD Department of Radiologoy University of California, San Diego School of Interview with: Dr. Rahul S. Desikan MD, PhD Department of Radiologoy University of California, San Diego School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Desikan: The MAPT gene encodes the tau protein, which plays an integral role in Alzheimer's disease (AD) neurodegeneration. Though a number of studies have investigated this issue, the role of the MAPT gene in Alzheimer's disease is still unclear. In contrast, a number of studies have found a robust association between MAPT and increased risk for other 'tauopathies' like Parkinson's disease (PD). In our study, rather than evaluating all possible genetic loci, we only assessed shared genetic variants between Alzheimer's disease and PD. By using this type of approach, we were able to increase our statistical power for gene discovery in Alzheimer's disease. We found genetic overlap between Alzheimer's disease and Parkinson's disease at a locus on chromosome 17 within the MAPT region. Our findings demonstrate that this MAPT associated locus increases risk for Alzheimer's disease, correlates with gene expression of MAPT and is associated with brain atrophy of the entorhinal cortex and hippocampus on longitudinal MRI scans. (more…)
Alcohol, Author Interviews, Personalized Medicine / 18.02.2015

Sean M. Murphy, Ph.D. Assistant Professor  Department of Health Policy & Administration Washington State University Interview with: Sean M. Murphy, Ph.D. Assistant Professor  Department of Health Policy & Administration Washington State University Medical Research: What is the background for this study? What are the main findings? Dr. Murphy: Professional healthcare advice regarding excessive alcohol consumption has been shown to reduce demand in a controlled setting. However, success in a clinical trial isn’t always indicative of an intervention’s effectiveness in everyday use. Studies testing the effect of provider advice on alcohol demand in a non-controlled environment are few, and have failed to control for non-moderate drinkers.  Therefore, it is possible that the estimated effect of professional-health advice primarily reflected moderate-drinkers’ responses. The distinction between moderate and non-moderate drinkers is an important one, as society bears a large cost for those who consume above-moderate quantities, while moderate drinkers have been shown to be relatively productive and healthy. Excise taxes may not be efficient given that they impose negative externalities on moderate drinkers, while excessive drinkers have been shown to be relatively unresponsive to price increases. We found that personalized information from a healthcare professional was negatively associated with reported alcohol consumption among both “risky” and “binge" drinkers. Moreover, we found that personalized drinking advice may have an impact on those who are reluctant to state that they were given such advice. (more…)
Author Interviews, Genetic Research, Personalized Medicine / 13.02.2015

Prof. Jozef Interview with: Prof. Jozef Gecz NH&MRC Senior Principal Research Fellow Professor of Human Genetics School of Paediatrics and Reproductive Health Faculty of Health Sciences The University of Adelaide at the Women's and Children's Hospital North Adelaide, SA Medical Research: What is the background for this study? What are the main findings? Prof. Gecz: Cerebral palsy is the most frequent movement disorder of children for many years considered to be due to brain injury. Given that cerebral palsy incidence has not changed dramatically over many years while medical care is constantly improving, we look for other causes and specifically genetic mutation. By investigating 183 children with cerebral palsy and for many also one or both of their parents we find that for at least 14% of these we can find plausible explanation in genetic mutation being involved in the causation of their cerebral palsy. Importantly, we find that 10% of these mutations are de novo, which means that these mutations are not present in the parents (specifically in their blood as that is the tissue source we tested). 4% of mutations were inherited from unaffected mothers to affected sons. Previous estimates suggested 2% genetic contribution to Cerebral palsy. We now know that it is at least 14% and likely more. If you are looking for compensation for this condition, contact an Indiana cerebral palsy lawyer. (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 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…)