AACR, Author Interviews, CT Scanning, Lung Cancer / 28.06.2019

MedicalResearch.com Interview with: [caption id="attachment_49973" align="alignleft" width="163"]Barbara Nemesure, PhD  Professor, Department of Family, Population and Preventive Medicine Division Head, Epidemiology and Biostatistics Director, Cancer Prevention and Control Program Director, Lung Cancer Program, Stony Brook Cancer Center Renaissance School of Medicine Stony Brook University   Dr. Nemesure[/caption] Barbara Nemesure, PhD Professor, Department of Family, Population and Preventive Medicine Division Head, Epidemiology and Biostatistics Director, Cancer Prevention and Control Program Director, Lung Cancer Program, Stony Brook Cancer Center Renaissance School of Medicine Stony Brook University    MedicalResearch.com: What is the background for this study? What are the main findings? Response: Lung cancer is the most common cause of cancer death, claiming the lives of more than 150,000 people in the United States each year. While lung nodules are not uncommon, it has remained a challenge to differentiate those that will progress to cancer and those that will remain benign. Although numerous risk prediction models for lung cancer have been developed over the past 2 decades, the majority have been based on retrospective analyses or high risk groups with a strong history of tobacco use. To date, there have been a limited number of large-scale, prospective studies evaluating risk that a nodule will convert to cancer in the general population. This investigation aimed to construct a population-based risk prediction model of incident lung cancer for patients found to have a lung nodule on initial CT scan. The derived model was determined to have high accuracy for predicting nodule progression to cancer and identified a combination of clinical and radiologic predictors including age, smoking history (pack-years), a personal history of cancer, the presence of chronic obstructive pulmonary disease (COPD), and nodule features such as size, presence of spiculation and ground glass opacity type. When compared to patients in the low risk category, those defined as high risk had more than 14 times the risk of developing lung cancer. Quantification of reliable risk scores has high clinical utility, enabling physicians to better stratify treatment plans for their patients.     
AACR, Author Interviews, Breast Cancer, Cancer Research, Surgical Research / 08.04.2019

MedicalResearch.com Interview with: [caption id="attachment_48432" align="alignleft" width="149"]Sharon S. Lum, MD, FACSProfessor in the Department of Surgery-Division of Surgical Oncology Medical Director of the Breast Health CenterLoma Linda University HealthLoma Linda University School of Medicine Dr. Lum[/caption] Sharon S. Lum, MD, FACS, Professor Department of Surgery-Division of Surgical Oncology Medical Director of the Breast Health Center Loma Linda University Health Loma Linda University School of Medicine  MedicalResearch.com: What is the background for this study?   Response: Anecdotally, we observed that many patients with advanced HER2+ breast cancer have had tremendous responses to the new targeted therapies and the oncologists were referring them back to surgeons for consideration of local regional therapy. While traditionally surgeons have avoided operating on metastatic breast cancer patients due to the patient’s likelihood of dying from their metastatic disease, these HER2+ patients seemed to be doing so well that surgery might make sense. In our surgical oncology clinic, we seemed to be operating more on these patients. Since these patients seemed to be living longer, they might survive long enough for their primary tumor to become a problem for them. However, we did not have any data to support doing surgery in these cases. Prior studies have demonstrated mixed results regarding the survival benefit from surgery for stage IV breast cancer patients, but these were completed prior to routine use of anti-HER targeted therapies, so we wanted to further examine the role of surgery in HER2+ stage IV breast cancer patients.
AACR, Author Interviews, Cancer Research, HPV, University of Michigan, Vaccine Studies / 05.04.2019

MedicalResearch.com Interview with: [caption id="attachment_48381" align="alignleft" width="157"]Diane Harper, M.D., M.P.H., M.S.Professor of Family Medicine and Obstetrics and GynecologySenior Associate Director, Michigan Institute for Clinical and Health ResearchPhysician Director for Community Outreach, Engagement and Health Disparities,Rogel Cancer CenterMichigan Medicine Dr. Harper[/caption] Diane Harper, M.D., M.P.H., M.S. Professor of Family Medicine and Obstetrics and Gynecology Senior Associate Director, Michigan Institute for Clinical and Health Research Physician Director for Community Outreach, Engagement and Health Disparities, Rogel Cancer Center Michigan Medicine  MedicalResearch.com: What is the background for this study? Response: There is no current cure for women with HPV infection that has progressed to CIN 2/3 disease. The only treatment is for the diseased cervix, and does not eliminate the risk of another CIN 2/3 from the HPV infection 15-20 years later. This vaccine is made from a live virus that has 3 genes inserted:  human cytokine IL-2, and modified forms of HPV 16 E6 and E7 proteins. When the vaccine is injected subcutaneously, the proteins for HPV 16/E6 and E7 and the cytokine LI-2 proteins are made. These proteins trigger the immune response.  This is very different form imiquimod which is topical and not specific for HPV.
AACR, Author Interviews, Cancer Research, Dental Research, Pancreatic, Race/Ethnic Diversity / 28.03.2019

MedicalResearch.com Interview with: [caption id="attachment_48243" align="alignleft" width="189"]Dr. Julie Palmer Dr. Palmer[/caption] Julie R. Palmer, ScD Professor, Boston University School of Medicine Associate Director, Slone Epidemiology Center at Boston University Boston, MA 02118  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Since 1995, 59,000 African American women from all regions of the U.S. have participated in a Boston University research study of the health of Black women.  Study participants complete mailed or online questionnaires every two years. Our major goal is to identify modifiable risk factors for cancers and nonmalignant conditions that disproportionately affect African Americans (e.g., pancreatic cancer, early-onset breast cancer, type 2 diabetes, uterine fibroids).  The reasons for the higher incidence of pancreatic cancer in African Americans relative to non-Hispanic White women in the U.S. are unknown. I was aware that several recent studies in predominantly White populations had observed a higher incidence of pancreatic cancer in those who had reported poor oral health and wondered whether the higher prevalence of poor oral health among African Americans could play a role in their higher incidence of pancreatic cancer.  We had already asked about gum disease, periodontal disease, and adult tooth loss in several rounds of data collection. After rigorous analysis, we found that women who reported any adult tooth loss had about two times the risk of future development of pancreatic cancer compared with those who had no tooth loss and had never reported periodontal disease. The estimated risk was even greater for those who had lost five or more teeth. A similar association was observed for reports of periodontal disease, but the association was not statistically significant.
AACR, Author Interviews, Biomarkers, MD Anderson / 05.03.2019

MedicalResearch.com Interview with: [caption id="attachment_47785" align="alignleft" width="200"]Vassiliki Papadimitrakopoulou, MDProfessor of MedicineDepartment of Thoracic/Head and Neck Medical OncologyMD Anderson Cancer Center in Houston Dr. Papadimitrakopoulou[/caption] Vassiliki Papadimitrakopoulou, MD Professor of Medicine Department of Thoracic/Head and Neck Medical Oncology MD Anderson Cancer Center in Houston MedicalResearch.com: What is the background for this study? What are the main findings? Response: 30% of patients with newly diagnosed advanced NSCLC can be treated successfully with targeted therapies, often yielding higher response rates than chemotherapy or immune checkpoint inhibitors. Selecting first-line therapy for patients with NSCLC requires assessment of an expanding list of guideline-recommended genomic biomarkers (EGFR, ALK, ROS1, BRAF, RET, MET amplification and exon 14 skipping, and ERBB2, with NTRK newly added) Standard-of-care (SOC) testing relies on tissue, which is limited by biopsy-related risks, specimen insufficiency, and lab processing duration, which hamper timely optimal treatment selection -          NILE is a large, prospective, multicenter, head-to-head study of SOC tissue-based genomic testing to plasma-based comprehensive cfDNA genomic testing (Guardant360®). For the four biomarkers with FDA approved therapies, up to 34% of patients were tested by SOC tissue testing versus 95% with cfDNA testing. NILE met its primary endpoint - cfDNA performed similar to tissue in the detection of guideline-recommended biomarkers and cfDNA results were delivered significantly faster than SOC tissue testing (median 9 days vs. 15 days).Using cfDNA testing first, 87% of patients with a guideline-recommended biomarker would have been detected, compared to 67% if SOC tissue testing was first.
AACR, Author Interviews, Colon Cancer / 04.03.2019

MedicalResearch.com Interview with: Ronit Yarden, PhD, MHSA Director of Medical Affairs Colorectal Cancer Alliance, a patient advocacy organization Washington, D.C.  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: The colorectal Cancer Alliance is a patient advocacy group (the largest advocacy group for colorectal cancer) and its mission is to provide support to patients, survivors, their caregivers and family members as well as advocate on their behalf for.  The organization is also committed to raise awareness for screening and early detection of colorectal cancer to help save lives and to provide funding for innovative colorectal cancer research. As part of our support we sought to identify some of the clinical, emotional and financial experiences and unmet needs of patients under 50 years old.  We conducted an online survey that was promoted through social media and 1195 patients and survivors completed our survey. 
AACR, Author Interviews, Cancer Research, MD Anderson, University Texas / 01.10.2018

MedicalResearch.com Interview with: [caption id="attachment_44913" align="alignleft" width="120"]Filip Janku, MD, PhD Associate Professor, Investigational Cancer Therapeutics (Phase I Clinical Trials Program) Center Medical Director, Clinical and Translational Research Center The University of Texas MD Anderson Cancer Center Houston, TX 77030 Dr. Janku[/caption] Filip Janku, MD, PhD Associate Professor, Investigational Cancer Therapeutics (Phase I Clinical Trials Program) Center Medical Director, Clinical and Translational Research Center The University of Texas MD Anderson Cancer Center Houston, TX 77030 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Clostridium novyi-NT is an attenuated strain of bacteria Clostridium, which induced a microscopically precise, tumor-localized response in a rat brain tumor model and in companion dogs bearing spontaneous cancers. Clostridium novyi-NT can only grow in hypoxic (low-oxygen) tumor environment and destroys cancer cells by secreting lipases, proteases, and other hydrolytic enzymes; recruiting inflammatory cells to tumors eliciting anti-tumor immune responses in animals. Furthermore, intratumoral injection can plausibly induce an immune mediated abscopal effect in non-injected tumor sites. Therefore, we designed a phase I dose-finding study to test for safety and tolerability of the single intratumoral injection of Clostridium novyi-NT in 24 patients with advanced cancers with no available standard therapies. We also designed experiments to study activation of antitumor immune response in blood and tumor samples from patients undergoing the therapy. We demonstrated that single dose of intratumoral injection of Clostridium novyi-NT is feasible and has led to significant destruction of injected tumor masses. Adverse events, which were often related to the tumor destruction at the infected site, could have been significant but mostly manageable. Correlative studies of pre-treatment and post-treatment tumor and blood samples suggested immune response to therapy.
AACR, Author Interviews, Biomarkers, Colon Cancer / 05.09.2018

MedicalResearch.com Interview with: [caption id="attachment_44230" align="alignleft" width="200"]Andrea Sottoriva, PhD, MSc Reader in Cancer Evolutionary Dynamics | Evolutionary Genomics & Modelling Lab Centre for Evolution and Cancer | The Institute of Cancer Research London Dr. Sottoriva[/caption] Dr. Andrea Sottoriva, PhD Centre for Evolution and Cancer, The Institute of Cancer Research, London, United Kingdom MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by a liquid biopsy? Response: Cetuximab is a targeted treatment available for metastatic colorectal cancer patients. Unfortunately, although many patients benefit from Cetuximab, after an initial response to the treatment many patients relapse and become resistant to the drug. We know that this resistance is due to the tumour evolving and adapting to therapy. Liquid biopsies allow to look for residual cancer DNA in the blood of a patient and hence monitor the emergence of resistance over time. We used blood samples take every 4 weeks (quite frequently for this type of study) to monitor the evolution of the cancers under treatment and see if there were some measurements that would predict if and when patients will relapse.
AACR, Author Interviews, Cancer Research, Imperial College, Kidney Disease / 20.08.2018

MedicalResearch.com Interview with: [caption id="attachment_43990" align="alignleft" width="128"]Dr. David Muller, PhD  Faculty of Medicine, School of Public Health Research Fellow in Epidemiology and Biostatistics Imperial College London Dr. Muller[/caption] Dr. David C. Muller PhD Faculty of Medicine, School of Public Health Research Fellow in Epidemiology and Biostatistics Imperial College, London MedicalResearch.com: What is the background for this study? What are the main findings? Response: Our colleagues in the U.S. have been working on KIM-1 for years, particularly in the context of chronic kidney disease. Recently they found that KIM-1 is also elevated at the time of diagnosis of kidney cancer. We wanted to see if KIM-1 concentrations could predict the chances of a future diagnosis of kidney cancer. We found that KIM-1 was a strong predictor of being diagnosis with kidney cancer in the next 5 years. We also found that higher pre-diagnostic KIM-1 was associated with worse survival after diagnosis. 
AACR, Author Interviews, Breast Cancer, Cancer Research, Lung Cancer / 01.08.2018

MedicalResearch.com Interview with: “smoking” by shira gal is licensed under CC BY 2.0Dr. Jose M. Martín-Sánchez IP of this study Grupo de Evaluación de Determinantes de Salud y Políticas Sanitarias Universitat Internacional de Catalunya Sant Cugat del Vallès Spain MedicalResearch.com: What is the background for this study? Response: Breast cancer has been the first cause of death from cancer among women. However, the mortality rates of breast cancer have been decreased in the last years. This downward trend can be attributed to treatment and screening programs. On the other hand, smoking has been increased among women during the last century and the main cause of lung cancer is smoking behavior. Based on this data, we hypothesized that the lung cancer mortality could outweigh the breast cancer mortality in the next years and the main purpose of this study was to project the mortality rates of lung cancer and breast cancer in women worldwide, based in previous data and using Bayesian methods, in order to identify potential strategies of public health to reduce the impact of lung cancer. Moreover, previous works described the lung and breast cancer mortality or projected one of them in a single country. For example, we have published two articles with data of Spain one of them with the description of lung cancer mortality trend in men and women and other with the projection of lung and breast cancer among women. The information of this study provides an overall point view around the word of this problem of public health.
AACR, Author Interviews, Cancer Research, Pancreatic / 02.07.2018

MedicalResearch.com Interview with: [caption id="attachment_42909" align="alignleft" width="163"]Michael J. Pishvaian, MD, PhD Phase I Program Director Assistant Professor Lombardi Comprehensive Cancer Center Washington, DC 20007 Dr. Pishvaian[/caption] Michael J. Pishvaian, MD, PhD Phase I Program Director Assistant Professor Lombardi Comprehensive Cancer Center Washington, DC 20007 MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Pancreatic cancer is a deadly disease and will soon be the second leading cause of cancer-related death. We have made some progress in the last few years....but despite this, patients with advanced, inoperable pancreatic cancer (which represents about 80% of pancreatic cancer patients) still only live 12 months, on average. We desperately need new therapies, AND to think "outside the box" for the treatment of pancreatic cancer. In that context, we have been learning that there are subgroups of patients with cancer whose tumors are particularly susceptible to certain therapies - either new therapies, or in some cases, approved therapies that would have not normally been used for that disease.  These specific patient subgroups with "actionable" findings have been identified through extensive genetic and molecular characterization of a patient's tumor. In the past there was a cynical perspective that pancreatic cancer did not harbor any "actionable" molecular abnormalities. We have now demonstrated that: 1) There are clearly and undeniably patients with pancreatic cancer whose tumors do indeed harbor "actionable" findings.  This represents at least 27% of pancreatic cancer patients, but may represent up to 50% as new therapies evolve.  These percentages are also highly consistent with similar publications in the pancreatic cancer field over the last few years; and 2) Importantly, we have been following our patients longitudinally for outcomes, and while it is still early, there is a statistically significant improvement in progression-free survival when a patient with a specific actionable molecular abnormality is treated with the appropriately "targeted" therapy.  This finding is also consistent with findings that have been observed in other cancer types.  
AACR, Aging, Author Interviews, Cancer Research, Immunotherapy, Melanoma / 21.06.2018

MedicalResearch.com Interview with: [caption id="attachment_42605" align="alignleft" width="200"]Ashani Weeraratna, Ph.D. The Ira Brind professor and  Co-program leader of the Immunology, Microenvironment and Metastasis Program  The Wistar Institute Member of Wistar’s Melanoma Research Center Philadelphia  Dr. Weeraratna[/caption] Ashani Weeraratna, Ph.D. The Ira Brind professor and Co-program leader of the Immunology, Microenvironment and Metastasis Program The Wistar Institute Member of Wistar’s Melanoma Research Center Philadelphia  MedicalResearch.com: What is the background for this study? What are the main findings?  Response:  This study shows for the first time that older patients, especially those who have had prior MAPKi therapy fare better than younger patients when treated with anti-PD1. We found that tumors in younger patients and younger mice have higher levels of Tregulatory cells, the cells that regulate other immune cells. This is not true systemically, only within the tumor microenvironment. We were surprised because we expected that, as with targeted therapy, older patients would have a poorer response to immunotherapy, given what we perceive as a poorer immune system in older patients. 
AACR, Author Interviews, Genetic Research / 18.04.2018

MedicalResearch.com Interview with: [caption id="attachment_41267" align="alignleft" width="200"]Ed Liu, M.D President and CEO The Jackson Laboratory (JAX) Dr. Ed Liu[/caption] Ed Liu, M.D President and CEO The Jackson Laboratory (JAX) MedicalResearch.com: What is the background for this study? What are the main findings? Response: A few years ago we and others identified a complex genomic instability profile commonly found in the genomes of breast, ovarian and endometrial carcinomas, which is characterized by hundreds of isolated head-to-tail duplications of DNA segments, called tandem duplications. We refer to this configuration as the tandem duplicator phenotype, or TDP. In this study, we perform a meta-analysis of over 2,700 cancer genomes from over 30 different tumor types and provide a detailed description of six different types of TDP, distinguished by the presence of tandem duplications of different sizes. Collectively, these profiles are found in ~50% of breast, ovarian and endometrial carcinomas as well as 10-30% of adrenocortical, esophageal, stomach and lung adeno-carcinomas. We show that distinct genetic abnormalities associate with the distinct TDPs, clearly suggesting that distinct molecular mechanisms are driving TDP formation. In particular, we provide strong evidence of a casual relationship between joint abrogation of the BRCA1 and TP53 tumor suppressor genes and the emergence of a short-span (~11 Kb) TDP profile. We also observe a significant association between hyper-activation of the CCNE1 pathway and TDP with medium-span (~230 Kb) tandem duplications, and between mutation of the CDK12 gene and medium- and large-span TDP (coexisting 230 Kb and 1.7 Kb tandem duplications). Importantly, we find that different forms of TDP result in the perturbation of alternative sets of cancer genes, with short-span TDP profiles leading to the loss of tumor suppressor genes via double transections, and larger-span TDP profiles resulting in the duplication (i.e. copy number gain) of oncogenes and gene regulatory elements, such as super-enhancers and disease-associated SNPs. 
AACR, Author Interviews, Baylor College of Medicine Houston, Blood Pressure - Hypertension, Pancreatic / 17.04.2018

MedicalResearch.com Interview with: [caption id="attachment_41101" align="alignleft" width="200"]Zhensheng Wang, M.P.H., Ph.D. Postdoctoral Associate Duncan Cancer Center-Bondy Baylor College of Medicine Houston, TX, US Dr. Wang[/caption] Zhensheng Wang, M.P.H., Ph.D. Postdoctoral Associate Duncan Cancer Center-Bondy Baylor College of Medicine Houston, TX MedicalResearch.com: What is the background for this study? Response: Our prior research consistently found a significant inverse association between circulating levels of soluble receptor for advanced glycation end products (sRAGE), an anti-inflammatory factor, and risk of pancreatic cancer. It has also been found that sRAGE levels or RAGE signaling are modulated by anti-hypertensive (anti-HT) medications, including angiotensin-converting-enzyme inhibitors (ACEi), β-blockers, and calcium channel blockers (CCBs). These medications have been shown in prior pre-clinical or experimental research to either increase sRAGE concentrations, decrease formation of advanced glycation end-products (AGEs), or dampen pro-inflammatory receptor for AGE (RAGE) signaling pathway. We therefore hypothesized that there would be an inverse association between use of anti-HT medications and risk of developing pancreatic cancer. Pancreatic cancer is a major public health concern in the United States, as it is the 4th leading cause of cancer-related mortality with an estimated of 43,090 deaths in 2017. Pancreatic cancer typically occurs in elderly individuals who also have chronic comorbid medical conditions, such as hypertension. Anti-HT medication use in individuals ≥ 18 years old has increased from 63.5% in 2001-2002 to 77.3% in 2009-2010, according to the National Health and Nutrition Examination Survey in the U.S. Therefore, it is of great public health significance to address the potential association between anti-HT medication use and risk of pancreatic cancer in the general population.
AACR, Author Interviews, Cancer Research / 17.04.2018

MedicalResearch.com Interview with: [caption id="attachment_41199" align="alignleft" width="200"]Mark E. Hatley, M.D., Ph.D. Assistant Member Molecular Oncology Division, Department of Oncology St. Jude Children's Research Hospital Memphis, TN 38105 Dr. Hatley[/caption] Mark E. Hatley, M.D., Ph.D. Assistant Member Molecular Oncology Division, Department of Oncology St. Jude Children's Research Hospital Memphis, TN 38105 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma occurring in children. Tumors appear histologically and genetically as undifferentiated skeletal muscle and are thus thought to solely originate from early skeletal muscle cells. However, tumors occur throughout the body, including sites devoid of skeletal muscle. In addition, tumor location is a key feature of staging and 40% of patients develop RMS in the head and neck. Interestingly, head and neck muscle development is distinct from the development of trunk and limb muscle. Previously we described a model of rhabdomyosarcoma which occurred specifically in the head and neck and originated from non-muscle cells. In this study we investigated how normal development programs are hijacked to drive rhabdomyosarcoma location. We demonstrated that RMS can originate from immature blood vessel cells that lie in between muscle fibers specifically in the head and neck. During development, these cells are hijacked, and become reprogrammed into rhabdomyosarcoma rather than mature endothelial cells. These RMS cells express factors important in head and neck muscle development. Our findings highlight that cell of origin contributes to RMS location and may explain why a high proportion of RMS occurs in the head and neck. 
AACR, Author Interviews, Cancer Research, Hepatitis - Liver Disease / 29.03.2018

MedicalResearch.com Interview with: [caption id="attachment_39686" align="alignleft" width="165"]In the United States, hepatitis A, hepatitis B and hepatitis C are the most common types, but also included are hepatitis D and E. CDC/ E.H. Cook, Jr. Hepatitis Virions
CDC/ E.H. Cook, Jr.[/caption] Dr. Monica Kasting PhD first author Dr. Anna Giuliano PhD Susan. T. Vadaparampil, Ph.D., M.P.H. Senior Member/Professor Center for Infection Research in Cancer H. Lee Moffitt Cancer Center, Tampa, Florida.Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center, Tampa, Florida  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: In the U.S., approximately 1 in 30 baby boomers are chronically infected with hepatitis C virus. Half of all cases of liver cancer are caused by hepatitis C and liver cancer is one of only three cancer types that are actually increasing in incidence in the US. Because of this, in 2012 the CDC issued a recommendation for universal screening for hepatitis C virus for everyone born between 1945 and 1965 (baby boomers). We wanted to look at the time period after that to see if the rates of screening in that population increased. From 2013-2015 screening among baby boomers only increased by 0.9% (from 11.8% to 12.7%) which indicates we still have a long way to go before we meet our goal of universal screening. 
AACR, Author Interviews, Microbiome, NYU, Pancreatic / 28.03.2018

MedicalResearch.com Interview with: [caption id="attachment_40819" align="alignleft" width="99"]Mautin Hundeyin MD Post-doctoral Research Fellow Dr. Hundeyin[/caption] Mautin Hundeyin MD Post-doctoral Research Fellow George Miller, MD is Principal Investigator and Director of the S. Arthur Localio Laboratory in the Department of Surgery at NYU School of Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Response: Pancreatic ductal adenocarcinoma (PDA) is the devastating disease with grim prognosis. The microbiome has emerged as a contributor to oncogenesis in a number of intestinal tract malignancies. We found that PDA is associated with a distinct stage-specific gut and pancreatic microbiome that drives disease progression by inducing intra-tumoral immune suppression. Targeting the microbiome protects against oncogenesis, reverses intra-tumoral immune-tolerance, and enables efficacy for check-point based immunotherapy. These data have implications for understanding immune-suppression in pancreatic cancer and its reversal in the clinic. 
AACR, Author Interviews, Cancer Research, Melanoma / 24.03.2018

MedicalResearch.com Interview with: Gao Zhang, Ph.D. Staff scientist in the Herlyn Lab The Wistar Institute MedicalResearch.com: What is the background for this study? Response: The past 7 years have witnessed the great success in treating patients with unresectable or metastatic melanoma. Despite the breakthrough of molecularly targeted therapies and immune checkpoint blockade therapies, a majority of patients have experienced the rapid tumor recurrence and progression, following the dramatic regression. There is an urgent and unmet need to treat therapy-resistant tumors.
AACR, Author Interviews, Colon Cancer / 20.03.2018

MedicalResearch.com Interview with: [caption id="attachment_40659" align="alignleft" width="173"]Darren D. Browning, PhD | Professor Department of Biochemistry and Molecular Biology, Medical College of Georgia at Augusta University Georgia Cancer Center, Augusta, Georgia 30912-2100 Dr. Darren Browning[/caption] Darren D. Browning, PhD | Professor Department of Biochemistry and Molecular Biology, Medical College of Georgia at Augusta University Georgia Cancer Center, Augusta, Georgia 30912-2100 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Cancer of the colon and rectum is one of the most commonly diagnosed and has a high mortality because it is often identified at an advanced stage. In the United States the average overall risk of having to deal with this disease at some point is around one in twenty-five, but the risk is much higher for people who have previously had polyps removed or if a close relative was diagnosed with colon cancer. The risk is even higher for patients with inflammatory bowel disease or heritable disorders such as familial adenomatous polyposis and lynch syndrome. While chemoprevention is clearly warranted, there are currently no drugs available that can reduce the risk for those predisposed to colorectal cancer. Previous work from our laboratory has shown that drugs like sildenafil that inhibit phosphodiesterase 5 (PDE5), have a profound effect on the epithelial lining of the intestine. Our recent work has shown that these drugs can prevent intestinal cancers in two different mouse models of human disease. While this class of drugs is best known for treating erectile dysfunction, due to a low side-effect profile they are also prescribed for long-term daily use to treat pulmonary arterial hypertension (PAH) and benign prostate hyperplasia
AACR, Alzheimer's - Dementia, Author Interviews, Cancer Research, Cognitive Issues, Colon Cancer, UCSF / 24.10.2017

MedicalResearch.com Interview with: [caption id="attachment_37702" align="alignleft" width="112"]Yingjia Chen, M.Sc, MPH, Ph.D. Postdoctoral Fellow University of California, San Francisco Dr. Chen[/caption] Yingjia Chen, M.Sc, MPH, Ph.D. Postdoctoral Fellow University of California, San Francisco  MedicalResearch.com: What is the background for this study? Response: Both colon cancer and dementia are prevalent among the elderly and have a high risk of co-occurrence. Previous studies found that patients with dementia were treated less aggressively. In this study, we hypothesized that presence of pre-existing dementia was associated with worse survival for stage III colon cancer patients, and that post-operative chemotherapy was on the causal pathway.
AACR, Author Interviews, Cancer Research, Dental Research, Menopause / 02.08.2017

MedicalResearch.com Interview with: [caption id="attachment_36194" align="alignleft" width="200"]Jean Wactawski-Wende, PhD Dean, SUNY Distinguished Professor Professor, Department of Epidemiology and Environmental Health School of Public Health and Health Professions University of Buffalo Dr. Wactawski-Wende[/caption] Jean Wactawski-Wende, PhD Dean, SUNY Distinguished Professor Professor, Department of Epidemiology and Environmental Health School of Public Health and Health Professions University of Buffalo MedicalResearch.com: What is the background for this study? What are the main findings? Response: There has been a growing interest in the role of periodontal disease in system chronic diseases, including cancer. We explored the association of periodontal disease history and incident cancer in the women's health initiative study of postmenopausal women. We found that women reporting periodontal disease history were at increased risk of developing cancer overall. In addition they were found to have significant increased risk of specific cancers including cancers of the lung, breast, esophagus, gallbladder and melanoma. The risk persisted after control for many other factors. In addition, the risk was seen in women regardless of their smoking history. Both ever smokers and never smokers were found to have increased risk of cancer associated with periodontal disease history.
AACR, Abuse and Neglect, Boehringer Ingelheim, Cancer Research / 11.07.2017

MedicalResearch.com Interview with: [caption id="attachment_35858" align="alignleft" width="167"]Dr. Jordi Bruix, MD Professor of Medicine University of Barcelona Director of the Barcelona Clinic Liver Cancer (BCLC) Group Liver Unit Hospital Clinic of Barcelona Dr. Bruix[/caption] Dr. Jordi Bruix, MD Professor of Medicine University of Barcelona Director of the Barcelona Clinic Liver Cancer (BCLC) Group Liver Unit Hospital Clinic of Barcelona MedicalResearch.com: What is the background for this study? What are the main findings? Response: The RESORCE Phase III pivotal trial is an international, multicenter, placebo-controlled trial which investigated the efficacy of Stivarga (regorafenib) in adults with Child-Pugh A and Barcelona Clinic Liver Cancer Stage Category B or C hepatocellular carcinoma (HCC) who had documented disease progression following first-line treatment with Nexavar (sorafenib). Trial participants were administered a daily oral 160mg dose (three weeks on/ one week off) of regorafenib plus best supportive care (BSC), or placebo plus BSC. Results from the trial demonstrated that participants treated with regorafenib experienced a statistically significant and clinically meaningful improvement in the study’s primary endpoint—overall survival (OS). Participants treated with regorafenib demonstrated a median overall survival of 10.6 months vs. 7.8 months with placebo. At ASCO 2017, an exploratory analysis evaluated the impact of baseline alpha-fetoprotein (AFP) and c-Met as predictors of poor prognosis in patients enrolled in the RESORCE trial (Abstract #4078).
AACR, Author Interviews, Biomarkers, Cancer Research, Prostate Cancer / 15.06.2017

MedicalResearch.com Interview with: [caption id="attachment_35328" align="alignleft" width="138"]Dr. Yong-Jie Lu Reader in Medical Oncology Centre for Molecular Oncology Barts Cancer Institute - a CR-UK Centre of Excellence Queen Mary University of London John Vane Science Centre, Charterhouse Square, LONDON Dr. Yong-Jie Lu[/caption] Dr. Yong-Jie Lu MBBS, MD, PhD Reader in Medical Oncology Centre for Molecular Oncology Barts Cancer Institute - a CR-UK Centre of Excellence Queen Mary University of London John Vane Science Centre, Charterhouse Square London MedicalResearch.com: What is the background for this study? Response: Identifying/monitoring the occurrence of metastasis and the prediction of the length that a patient may survive with a prostate cancer is critical for doctors to select the proper treatment, aiming to achieve the best control of the cancer with a balance of quality of life. Currently this is achieved mainly by analysing the cancer tissues acquired through very invasive procedures or by expensive imaging techniques, most of which expose the patient to toxic radioactive materials. Circulating tumour cells (CTCs), which play a key role in the metastasis process, have been shown for their potential to be used for cancer prognosis by a simple blood sample analysis. However, previous CTC studies mainly detect the epithelial type of CTCs. Using the ParsortixTM (ANGLE plc) cell-size and deformability based CTC isolation system, we analysed not only epithelial CTCs, but also CTCs with epithelial-mesenchymal transition (EMT), a cellular process associated with cancer invasion and metastasis.
AACR, Author Interviews, Cancer Research, Genetic Research / 08.05.2017

MedicalResearch.com Interview with: Dr. Youzhi Li Vice President at Boston Biomedical  MedicalResearch.com: What are the main findings? Response: RNAi (RNA interference) technology has the potential to target any genes causing disease, including conventionally “undruggable” targets in cancer. One particularly interesting RNAi target in oncology is the CTNNBI oncogene, which encodes the β-Catenin protein whose nuclear form acts as a transcription factor promoting tumorigenesis. Aberrant β-Catenin signaling has been demonstrated in 90 percent of colorectal carcinomas, 40 percent of hepatocellular carcinoma, and 90 percent of non-ductal pancreatic carcinomas. Recent research also suggests active β-Catenin contributes to tumor immune evasion and to the recurrence of melanoma in patients post the check-point blockage immunotherapy. However, the direct blockade of β-Catenin activity has proved difficult with conventional approaches. While the application of traditional RNAi technology has the potential to block this pathway, in clinical cancer therapy, this approach has proven challenging due to the difficulty in systemic delivery of RNAi to tumor sites located in various organs. We have recently developed BBI-801, a lipid-based nanoparticle that encapsulates therapeutic aiRNAs targeting CTNNB1 and PD-L1 to simultaneously target immune evasion via both these pathways. Here, we investigate the in vivo delivery and anti-tumor activity of BBI-801.
AACR, Author Interviews, Biomarkers, Brigham & Women's - Harvard, Cancer Research, Immunotherapy, Neurology, Radiology / 01.05.2017

MedicalResearch.com Interview with: [caption id="attachment_34227" align="alignleft" width="145"]Ben Larimer, PhD research fellow in lab of Umar Mahmood, MD, PhD Massachusetts General Hospital Professor, Radiology, Harvard Medical School Dr. Ben Larimer[/caption] Ben Larimer, PhD research fellow in lab of Umar Mahmood, MD, PhD Massachusetts General Hospital Professor, Radiology, Harvard Medical School MedicalResearch.com: What is the background for this study? What are the main findings? Response: Although immunotherapies such as checkpoint inhibitors have revolutionized cancer treatment, unfortunately they only work in a minority of patients. This means that most people who are put on a checkpoint inhibitor will not benefit but still have the increased risk of side effects. They also lose time they could have spent on other therapies. The ability to differentiate early in the course of treatment patients who are likely to benefit from immunotherapy from those who will not greatly improves individual patient care and helps accelerate the development of new therapies. The main purpose of our study was to find a way to separate immunotherapy responders from non-responders at the earliest time point possible, and develop an imaging probe that would allow us to distinguish this non-invasively. Granzyme B is a protein that immune cells use to actually kill their target. They keep it locked up in special compartments until they get the right signal to kill, after which they release it along with another protein called perforin that allows it to go inside of tumor cells and kill them. We designed a probe that only binds to granzyme B after it is released from immune cells, so that we could directly measure immune cell killing. We then attached it to a radioactive atom that quickly decays, so we could use PET scanning to noninvasively image the entire body to see where immune cells were actively releasing tumor-killing granzyme B. We took genetically identical mice and gave them identical cancer and then treated every mouse with checkpoint inhibitors, which we knew would result in roughly half of the mice responding, but we wouldn’t know which ones until their tumors began to shrink. A little over a week after giving therapy to the mice, and before any of the tumors started to shrink, we injected our imaging probe and performed PET scans. When we looked at the mice by PET imaging, they fell into two groups. One group had high PET uptake, meaning high levels of granzyme B in the tumors, the other group had low levels of PET signal in the tumors. When we then followed out the two groups, all of the mice with high granzyme B PET uptake ended up responding to the therapy and their tumors subsequently disappeared, whereas those with low uptake had their tumors continue to grow. We were very excited about this and so we expanded our collaboration with co-authors Keith Flaherty and Genevieve Boland to get patient samples from patients who were on checkpoint inhibitor therapy to see if the same pattern held true in humans. When we looked at the human melanoma tumor samples we saw the same pattern, high secreted granzyme levels in responders and much lower levels in non-responders.
AACR, Author Interviews, Cancer Research, Genetic Research, Hepatitis - Liver Disease / 18.04.2017

MedicalResearch.com Interview with: Sara Torrecilla Recio PhD Student Mount Sinai Liver Cancer Program - Division of Liver Diseases Icahn School of Medicine at Mount Sinai New York, NY MedicalResearch.com: What is the background for this study? Response: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, which represents the second-leading cause of cancer related death worldwide. The landscape of molecular alterations in HCC has been thoroughly explored using next-generation sequencing technologies in single biopsies of tumors. However, in the recent years it has been demonstrated that not all the regions of a tumor harbor the same molecular alterations. This intra-tumor heterogeneity may lead to a misinterpretation of the molecular landscape of the malignancy since not all the molecular alterations would be captured by single-biopsies.
AACR, Author Interviews, Biomarkers, Cancer Research / 06.04.2017

MedicalResearch.com Interview with: [caption id="attachment_33719" align="alignleft" width="191"]Poulikos I. Poulikakos, PhD Assistant Professor Department of Oncological Sciences Department of Dermatology The Tisch Cancer Institute Icahn School of Medicine at Mount Sinai Dr. Poulikakos[/caption] Poulikos I. Poulikakos, PhD Assistant Professor Department of Oncological Sciences Department of Dermatology The Tisch Cancer Institute Icahn School of Medicine at Mount Sinai MedicalResearch.com: What is the background for this study? Response: Mutations in the oncoprotein kinase BRAF are found in about 8% of human tumors, including more than 50% of melanomas. Small molecule RAF inhibitors prolonged survival of melanoma patients with mutant-BRAF tumors, but resistance limits their effectiveness. Further, RAF inhibitors showed only modest efficacy in patients with colorectal and thyroid mutant-BRAF tumors. Previous studies have suggested that the complex biochemical mechanisms of action of RAF inhibitors account for both sensitivity and major mechanisms of resistance to these drugs. Recently, a number of next generation RAF inhibitors have entered preclinical or clinical development, but the most appropriate clinical context for their use remained elusive.
AACR, Author Interviews, Lung Cancer, Surgical Research / 06.04.2017

MedicalResearch.com Interview with: [caption id="attachment_33534" align="alignleft" width="177"]Emanuela Taioli MD PhD Professor, Population Health Science and Policy, and Thoracic Surgery Director, Institute for Translational Epidemiology Director, Center for the Study of Thoracic Diseases Outcome Director, Division of Social Epidemiology Icahn Medical Institute, New York, NY 10029 Dr. Taioli[/caption] Emanuela Taioli MD PhD Professor, Population Health Science and Policy, and Thoracic Surgery Director, Institute for Translational Epidemiology Director, Center for the Study of Thoracic Diseases Outcome Director, Division of Social Epidemiology Icahn Medical Institute, New York, NY 10029  MedicalResearch.com: What is the background for this study? Response: Extensive literature documenting the relationship between hospital volume and clinical outcomes has resulted in the centralization of cancer care advocating patients to seek cancer surgical procedures at high-volume (HV) hospitals. Lung resection and cystectomy have been specifically recommended for centralization, but improvements in outcomes are not shared equally among racial groups. It has also been reported that black patients more commonly undergo surgery at low-volume and lower-quality hospitals, despite living in close proximity to higher quality hospitals. We investigated the effects of centralization on HV hospital utilization and surgical outcomes for lung (n = 28,047 White; n = 2,638 Black) and bladder (n = 7,593 White; n = 567 Black) cancer patients over a 15 year time span (1997-2011) in New York State. We hypothesized that centralization has improved utilization of HV hospitals and outcomes for both black and white patients, but significant disparities remain between black and white patients.
AACR, Author Interviews, Diabetes, Genetic Research, Melanoma / 01.03.2017

MedicalResearch.com Interview with: [caption id="attachment_32560" align="alignleft" width="200"]Reeti Behera, Ph.D. Postdoctoral fellow in the Weeraratna lab The Wistar Institute Philadelphia PA Dr. Behera[/caption] Reeti Behera, Ph.D. Postdoctoral fellow in the Weeraratna lab The Wistar Institute Philadelphia PA MedicalResearch.com: What is the background for this study? What are the main findings? Response: Malignant melanoma is an aggressive disease and is the cause of the majority of skin cancer deaths. In particular, older individuals have a much poorer prognosis for melanoma and are more resistant to targeted therapy than compared to young individuals. A recently published study from our lab has shown that age-related changes in secreted factors in the microenvironment can drive melanoma progression and therapy resistance. Klotho is a protein whose expression levels decreases with aging. In this study, we have shown that a decrease in klotho levels in the aged microenvironment drives melanoma aggression and therapy resistance by promoting the oncogenic signaling pathway Wnt5A. We also have shown that reconstituting klotho levels in the aged microenvironment by using rosiglitazone, an FDA-approved drug used to treat diabetes, can reduce tumor burden in aged mice. We also show that Klotho expression is decreased in therapy-resistant melanoma tumors. Reconstituting klotho levels in therapy-resistant melanoma cells by treating with rosiglitazone can inhibit Wnt5A levels and MAPK pathway. We also show that rosiglitazone can significantly decrease therapy-resistant tumor burden in the aged mice, but not in the young.