Author Interviews, Cancer Research, Nature, NYU, Pancreatic / 17.03.2023

MedicalResearch.com Interview with: Aristotelis Tsirigos, Ph.D. Professor of Medicine and Pathology Co-director, Precision Medicine Director, Applied Bioinformatics LaboratoriesNew York University School of Medicine MedicalResearch.com: What is the background for this study? Response: Pancreatic cancer is one of the most lethal types of cancer with only 12% of patients surviving more than 5 years after diagnosis. One of the main reasons behind the dismal prognosis is the complexity of the tumor. Pancreatic cancer cells are very heterogenous and interact with different types of non-malignant cells in what is known as the tumor microenvironment. (more…)
Author Interviews, Cancer Research, Nature, Pancreatic, University of Michigan / 03.06.2022

MedicalResearch.com Interview with: Imad Shureiqi, MD, MS Professor, Division of Hematology and Oncology Department of Internal Medicine Rogel Cancer Center Ann Arbor, MI, 48109 MedicalResearch.com:  What is the background for this study?   Response: Pancreatic ductal adenocarcinoma is a highly lethal form of cancer with rising occurrence, and strategies to prevent and treat the disease are urgently needed. Most cases of pancreatic cancer arise from pre-cancerous lesions called pancreatic intraepithelial neoplasia (PanIN); about 55-80% of adults over forty are estimated to have these low-grade pre-cancerous silent pancreatic lesions. But critical factors that promote the progression of pancreatic pre-cancerous lesions to pancreatic cancer remain poorly defined, especially those easy to target. Findings from this publication indicate that people who have silent PanIN pre-cancerous lesions, even those that are low-grade, could increase their risk of PanIN progression into pancreatic cancer by consuming activators of a nuclear lipid receptor called peroxisome proliferator-activated receptor-delta (PPARδ). PPARδ activators can be natural substances, such certain fatty acids like palmitic and arachidonic acid in high-fat diets, or synthetic ones, like Cardarine (GW501516). (more…)
Author Interviews, Biomarkers, BMJ, Gastrointestinal Disease, Pancreatic / 09.03.2022

MedicalResearch.com Interview with: Ece Kartal, PhD Postdoctoral Fellow Saez-Rodriguez Group Universitätsklinikum Heidelberg Institute for Computational Biomedicine Heidelberg MedicalResearch.com:  What is the background for this study?    Response: Pancreatic cancer is one of the deadliest types of cancer: although incidence rates are relatively low (only few people develop pancreatic cancer in their lifetimes), it has a high lethality, with a five year survival rate of less than ~5%. Pancreatic cancer symptoms are generally unspecific so that the disease is usually detected very late which further  limits therapeutic options. In light of this, earlier detection of pancreatic cancer could dramatically improve prognosis, but there are currently no affordable and non-invasive tests available in the clinic. For pancreatic ductal adenocarcinoma (PDAC),the most common form of pancreatic cancer, it was previously found that the oral, gut and pancreatic microbiome are risk factors and may affect prognosis . (more…)
Author Interviews, Gender Differences, Pancreatic, Race/Ethnic Diversity / 23.05.2021

MedicalResearch.com Interview with: Kelly Herremans, MD Lead researcher on the study Surgical research fellow University of Florida College of Medicine Gainesville MedicalResearch.com: What is the background for this study? Response: Pancreatic cancer is a deadly malignancy with an estimated 5-year survival rate of only 9%. Significant racial and ethnic disparities exist in pancreatic cancer. Underrepresentation in the clinical trials that determine safety and efficacy may contribute to these disparate outcomes. (more…)
Author Interviews, Opiods, Pancreatic, PLoS / 08.01.2021

MedicalResearch.com Interview with: Faraz Bishehsari, MD, PhD Associate Professor of Medicine and Graduate College Director of the Translational Gastroenterology Unit Division of Digestive Diseases Rush University Medical Center MedicalResearch.com: What is the background for this study? Response: This study builds on recent population based studies where opium use was found to be possible risk factor for pancreatic cancer. Although opium use is not a common recreational habit in the United States, opioid use has been rising remarkably over the past decade. In fact, opioid misuse and overdose have evolved into a public health crisis here with increasing opioid prescription use and abuse over the past decade. (more…)
Author Interviews, Diabetes, Genetic Research, Pancreatic / 15.05.2020

MedicalResearch.com Interview with: Dr. Núria Malats, MD PhD, Head of the Genetic and Molecular Epidemiology Group Spanish National Cancer Research Centre (CNIO)  MedicalResearch.com: What is the background for this study? Response: The high mortality of pancreatic cancer is a consequence of late diagnosis because of the absence of symptoms in the earliest stages, and defining risk populations is therefore crucial to be able to carry out diagnostic tests that reveal the presence of the tumour as early as possible. Diabetes and pancreatic cancer are connected because the pancreas secretes insulin; in diabetic people, this does not occur in a normal way. It is estimated that around 50% of patients with pancreatic cancer presents diabetes. But it is an outstanding challenge for researchers to figure out which is the cause and which is the consequence.  To conduct the study, the team used data from more than 3,500 persons from PanGenEU, a large European study involving centres from six countries, including Spain, and led by Malats, to analyse the relationship between multiple risk factors and pancreatic cancer. (more…)
Author Interviews, Colon Cancer, Gastrointestinal Disease, Pancreatic / 17.04.2020

MedicalResearch.com Interview with: Dr Cristina Bosetti PhD Head of the Unit of Cancer Epidemiology Mario Negri Department of Oncology Milan Italy MedicalResearch.com: What is the background for this study? Response: Aspirin has been known since long time to have a beneficial effect in the primary and secondary prevention of cardiovascular diseases. Additional evidence indicates that it has also a favorable role on the risk of various cancers. (more…)
AACR, Author Interviews, Pancreatic / 24.09.2019

MedicalResearch.com Interview with: Hadas Reuveni, PhD VP of Research and Development Kitov Pharma MedicalResearch.com: What is the background for this study? Response: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death worldwide. Current treatments fail to provide patients with an effective and long-lasting response, mostly given to the nature of the tumor microenvironment which hinders drug accessibility, the late stage on diagnosis and the rapid upregulation of compensatory alternative signaling pathways by the tumor cells that lead to cancer drug resistance. Two of the major parallel pathways regulating tumor survival and metastasis as well as the crosstalk of the tumor and its microenvironment are mediated by insulin receptor substrate (IRS) 1 and 2, and by the signal transducer and activator of transcription 3 (STAT3). Both IRS1 and STAT3 have been shown to play a significant role in development of drug resistance by tumor cells. NT219, the focus of the current study, is a small molecule that presents a new concept in cancer therapy. NT219 represents a new family of novel compounds acting as a dual inhibitor of both IRS1/2 and STAT3 signaling both directly in the tumor and its microenvironment. We have previously shown that simultaneous inhibition of these two pathways is crucial to overcome drug resistance, and to prolong the positive response of the anti-cancer activity of approved cancer drugs. NT219 targets IRS1/2 for degradation using a unique mechanism, supported by a feed-forward decrease in IRS gene expression. A long-term suppression of both IRS and STAT3 by NT-219 has been demonstrated in previous preclinical studies, which lasted days following removal of NT219 from the cancer cells, assuring a strong and prolonged anti-cancer activity. This study was designed to investigate the efficacy of NT219 at overcoming drug resistance to several approved oncology therapies using patient-derived xenograft (PDX) models of KRAS mutant pancreatic cancer, as well as to validate NT219's mechanism of action and optimal dose regimen.  (more…)
Author Interviews, JAMA, Mayo Clinic, Pancreatic, USPSTF / 14.08.2019

MedicalResearch.com Interview with: Dr. Chyke A. Doubeni, M.D., M.P.H. Dr. Doubeni is a family physician and The inaugural director of the Mayo Clinic Center for Health Equity and Community Engagement Research MedicalResearch.com: What is the background for this study? Response: The U.S. Preventive Services Task Force uses systematic review of existing research to make recommendations on clinical preventive services that are delivered in primary care, with the goal to promote and improve health for all Americans. Although pancreatic cancer is an uncommon condition in the general population, it is often deadly. Pancreatic cancer is now the third most common cause of cancer death in the United States, and could become the second leading cause if current trends continue. The vast majority of people with pancreatic cancer are diagnosed at a late stage and, unfortunately, even when caught early enough when surgery could be most effective, only a little over one-third of patients survive beyond five years. (more…)
AACR, Author Interviews, Cancer Research, Dental Research, Pancreatic, Race/Ethnic Diversity / 28.03.2019

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Cancer Research, NEJM, Pancreatic / 21.12.2018

MedicalResearch.com Interview with: Prof. Thierry Conroy MD, Director Department of Medical Oncology Institut de Cancérologie de Lorraine Vandoeuvre-lès-Nancy CEDEX MedicalResearch.com: What is the background for this study? Response:  Surgery of pancreatic cancer offers the only chance of cure. Despite the low response rate (5% - 9%) of gemcitabine in metastatic disease, a 6-month regimen of adjuvant therapy with gemcitabine increases 5-year survival from 10% to 20% and is recognized as standard of care. However, recurrence rate remain high despite adjuvant treatment with 69-75% of patients relapsing within 2 years. -       The combination of bolus and continuous infusion Fluorouracil, Folinic Acid, Irinotecan and Oxaliplatin (Folfirinox) was shown to increase response rate (31.6% versus 9.4%) in metastatic disease as compared to Gemcitabine and increase survival (11.1 versus 6.8 months). -       Deletion of bolus Fluorouracil in the Folfirinox regimen (mFOLFIRINOX) decreased toxicity and do not reduce efficacy in advanced disease. -       We performed a randomized trial in patients with good performance status, ECOG 0-1 CA 19.9 ≤ 180 U/L and no cardiac contraindication to fluorouracil. (more…)
Author Interviews, Immunotherapy, Pancreatic / 14.11.2018

MedicalResearch.com Interview with: Dr James Kuo, MBBS Medical oncologist and Deputy Medical Director Scientia Clinical Research Sydney, Australia MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Immune checkpoint inhibitors (ICI) that have seen success in the treatment of patients with various tumour types have not been as effective in patients with metastatic pancreatic cancer and therefore immune-therapeutic agents of novel mechanism of action, in particular in combination with existing ICI, need to be investigated. This study set out to test the safety and efficacy of pixatimod, a novel immunomodulatory agent, in combination with nivolumab, firstly in the dose escalation cohorts in patients with any solid tumour for the maximal tolerable dose, and then using this dose to further treat an expansion cohort of patients with pancreatic cancer. Altogether 16 patients had received the combination and in 10 patients in whom treatment response was evaluable, 4 patients experienced a clinical benefit and continued treatment in the trial, with 1 patient having a significant partial response now treated for 48 weeks. Interestingly, all these 4 patients had metastatic colorectal cancer. Side effect profile has been consistent with other immunotherapeutic agent combination and in the patients who had clinical benefit, no treatment related side effects were observed.  (more…)
Author Interviews, Cancer Research, Cannabis, Pancreatic / 01.08.2018

MedicalResearch.com Interview with: Prof Marco Falasca Head Metabolic Signalling Group School of Pharmacy & Biomedical Sciences Faculty of Health Sciences Curtin University Western University MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Each year around 9,800 people in the UK are diagnosed with pancreatic cancer. The disease is particularly aggressive and has one of the lowest survival rates of all cancers. Indeed, the life expectancy for pancreatic cancer patients has barely changed in the last 40 years because there are very few, and mostly only palliative care, treatments available. Given the five-year survival rate for people with pancreatic cancer is less than seven per cent, the discovery of new treatments and therapeutic strategies is urgently needed. In this study, we decided to concentrate on a protein, named GPR55, found in high levels in pancreatic cancer. Our results show that GPR55 promotes pancreatic cancer progression. Consequently, we decided to use its inhibitor cannabidiol, a naturally occurring constituent of medicinal cannabis, as a pharmacological strategy to block GPR55 activity. Strikingly, mice with pancreatic cancer that were treated with cannabidiol alongside chemotherapy, survived almost three times longer than those treated with chemotherapy alone, our study reports.  (more…)
AACR, Author Interviews, Cancer Research, Pancreatic / 02.07.2018

MedicalResearch.com Interview with: 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.   (more…)
ASCO, Author Interviews, Pancreatic / 04.06.2018

MedicalResearch.com Interview with: Dr. Marcus Smith Noel, MD University of Rochester James P. Wilmot Cancer Institute Strong Memorial Hospital MedicalResearch.com: What is the background for this study? What are the main findings? Response: Pancreatic cancer outcomes are poor even despite improvement in the overall prognosis for many cancers. Early detection of pancreatic cancer is uncommon because early stage pancreatic cancer often has few symptoms. Unfortunately, most cases are diagnosed at more advanced stages, which is in part why the disease is so lethal. Current standard of care treatments are highly toxic and not effective long-term, as about 90% of patients diagnosed with advanced or metastatic pancreatic cancer do not survive a year. SM-88 is a relatively non-toxic novel combination therapy designed to utilize cellular metabolism and oxidative stress to drive cancer cell death. This therapy has previously demonstrated activity in various metastatic cancers, such as pancreatic cancer, and is currently being evaluated in an ongoing Phase II trial for metastatic pancreatic cancer. This study is a trial in progress report of Tyme’s Phase II trial in patients with metastatic cancer. The Phase II trial is designed as an open-label, multi-center study of SM-88 in patients with metastatic pancreatic cancer who have failed at least one prior line of therapy. In the first stage of the trial, 36 patients will be randomized 1:1 to receive a dose of either a currently utilized active regimen or a double dose per day of SM-88. Primary endpoints are overall response rate (ORR) and overall survival (OS). Secondary endpoints include progression-free survival (PFS), disease control rate, duration of response and time to subsequent treatment. The purpose of the first stage of the study is to analyze the safety, efficacy and pharmacokinetics of SM-88 in patients.  The selected dose of SM-88 will be continued into the second stage of the trial for approximately 81 additional patients. (more…)
AACR, Author Interviews, Baylor College of Medicine Houston, Blood Pressure - Hypertension, Pancreatic / 17.04.2018

MedicalResearch.com Interview with: 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. (more…)
AACR, Author Interviews, Microbiome, NYU, Pancreatic / 28.03.2018

MedicalResearch.com Interview with: 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.  (more…)
Author Interviews, Cancer Research, Novartis, Pancreatic / 05.02.2018

MedicalResearch.com Interview with: Lynn Matrisian, PhD, MBA Chief science Officer Pancreatic Cancer Action Network MedicalResearch.com: Would you tell us a little about PNETs? How common is this type of pancreatic tumor? How does Lutathera differ from other treatments for this tumor?  Response: Pancreatic neuroendocrine tumors (PNETs) make up about 6 percent of all pancreatic cancer diagnoses. They are less common and slower growing than the more common type of pancreatic cancer, adenocarcinoma, and have a better prognosis. Lutathera® is a peptide receptor radionuclide therapy (PRRT) that was approved for the treatment of gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including PNETs, that express somatostatin receptors. The drug is a somatostatin analog that is conjugated to a radionuclide (177Lu) to selectively deliver radiotherapy to the cancer cells. Other treatment options for PNETs include surgery (partial or complete removal of the tumor), chemotherapy (typically in combination) or radiation therapy (conventional as well as PRRT). Patients may also receive targeted therapies. Sutent® blocks platelet-derived growth factor receptors (PDGFRs) α and β, stem-cell factor receptor (c-kit) and vascular endothelial growth factor receptor (VEGFR)-2 and VEGFR-3, leading to inhibition of cell growth and angiogenesis. Afinitor® behaves as a rapamycin analog, blocking the mammalian target of rapamycin (mTOR) signaling pathway. Prior to Lutathera’s approval, there were two non-PRRT somatostatin analogs approved for PNET patients. These drugs were initially intended to mitigate some of the symptoms of the disease, but they were also found to slow the cancer cells’ growth. The approved somatostatin analogs are lanreotide and octreotide.  (more…)
Author Interviews, Genetic Research, JAMA, Pancreatic, Surgical Research / 25.08.2017

MedicalResearch.com Interview with: Nancy You, MD, MHSc, FACS Department of Surgical Oncology The University of Texas MD Anderson Cancer Center Houston  MedicalResearch.com: What is the background for this study? What are the main findings? Response: This study was motivated by the emerging promise of precision medicine and the emerging evidence that immunotherapy may have phenomenal efficacy in particular molecular subtypes of cancers.  This specific molecular subtype shows deficiency in DNA mismatch repair mechanisms and therefore is thought to be more immunogenic.  DNA mismatch repair deficiency can arise from germline defects such as in the case of patients with Lynch Syndrome, an inherited cancer syndrome, or from epigenetic inactivation DNA mismatch repair genes. Overall, pancreas cancer has seen limited success with conventional chemotherapy.  In our study, we demonstrated that there is a particular molecular subtype of pancreas cancer that is characterized by defect in DNA mismatch repair genes and by microsatelie instability that has a different prognosis than other pancreas cancers.  This subtype of pancreas cancer is suspected to also respond to immunotherapy. (more…)
Author Interviews, Biomarkers, Pancreatic / 13.06.2017

MedicalResearch.com Interview with: Rajesh Kumar NV, Ph.D. Instructor of Oncology and Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA Current affiliation Senior Manager, Human Therapeutics Division, Intrexon Corporation Germantown, MD MedicalResearch.com: What is the background for this study? Response: Pancreatic ductal adenocarcinoma (a.k.a. pancreatic cancer) is one of the most deadly of all types of cancer and currently the third leading cause of cancer-related death in United States. Current therapeutic options for pancreatic cancer involve combination cytotoxic chemotherapy, which yield only minimal survival benefit. A multitude of Phase III clinical trials have failed to demonstrate efficacy, largely due to the aggressive growth of pancreatic tumors. Metabolic reprogramming is a hallmark of cancer cells, including pancreatic cancer. Altered metabolism is central to the pathogenesis of pancreatic cancer and contributes to promotion of proliferation, survival, invasiveness and chemo-resistance of cancer cells. Pharmacologic strategies targeting cancer metabolism might therefore represent a promising approach towards the development of effective drugs against pancreatic cancer. We utilized a clinically relevant and genetically characterized platform of patient-derived pancreatic cancer xenografts, which we originally created from the freshly resected pancreatic cancer tissues of patients, to explore the in vivo anti-tumor efficacy of a panel metabolic inhibitors and investigated whether mutational status, gene expression and metabolite profile of tumors correlate with the sensitivity to metabolic inhibitors. To our knowledge, this is the largest preclinical trial which enrolled a large number of animals (over 500 mice) with established human pancreatic tumors for the comprehensive evaluation of key metabolic inhibitors in pancreatic cancer.  (more…)
Author Interviews, Biomarkers, Immunotherapy, Pancreatic / 21.10.2016

MedicalResearch.com Interview with Dr. Ashton A. Connor, MD PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research Dr. Steven Gallinger MD, MSC Division of General Surgery Toronto General Hospital Toronto, ON MedicalResearch.com: What is the background for this study? What are the main findings? Response: The etiology of pancreatic ductal adenocarcinoma (i.e. "pancreatic cancer") and the relationship between the tumour and its characteristic dense, encroaching stroma are still poorly understood. Using whole genome sequencing in two large cohorts, we show that there are four fundamental mutational processes that give rise to pancreatic cancer. With expression data, we also show that the interaction between the tumour and the surrounding stroma varies with the type of mutational process found in the tumour. Specifically, tumours with defective DNA repair, either homologous recombination or mismatch repair deficiency, elicited strong anti-tumour immune responses, likely due to the relatively high numbers of neoantigens in these tumours. Individually, these concepts have been studied in other cancer types, but we are first to apply either of these to pancreatic cancer, and we also the first to integrate these two aspects of cancer biology for any tumour, to our knowledge. (more…)
Author Interviews, Gastrointestinal Disease, Pancreatic / 06.10.2016

MedicalResearch.com Interview with: Dr. Pouria Jandaghi Functional Genome Analysis, Deutsches Krebsforschungszentrum Heidelberg, Germany Department of Human Genetics, McGill University University and Genome Quebec Innovation Centre Montreal, Canada MedicalResearch.com: What is the background for this study? Response: Although the overall five-year survival of all patients with cancer stands at 63%, for pancreatic cancer patients, it is a disheartening 8% - a number that remains largely unchanged for three decades. Of the patients diagnosed with pancreatic cancer, about 85% exhibit pancreatic ductal adenocarcinoma (PDAC). Most of these patients die within 4 to 6 months after diagnosis. The poor prognosis is caused by the its detection at only late stages, and lack of effective options for chemotherapy. The widely used chemotherapeutic agent gemcitabine, confers a median survival advantage of only 6 months, and resistance to therapy develops in the vast majority of patients. Given this poor prognosis of patients with PDAC, there is an urgent need to find more effective therapies. In this study, we set out to investigate potential therapeutic targets by dissecting gene expression profiles of tumors and control samples. Candidate targets were validated with respect to their suitability and analyzed functionally. (more…)
Author Interviews, Biomarkers, Diabetes, Pancreatic / 19.09.2016

MedicalResearch.com Interview with: Dr. Pavel Škrha Charles University, Prague Czech Republic MedicalResearch.com: What is the background for this study? What are the main findings? Response: Incidence of pancreatic cancer (PAC) is still increasing. The main problem is in the late diagnosis of the cancer. It was found, that diabetes mellitus was much more frequent in the pancreatic cancer patients than in the general population. DM can be already the first symptom of the disease (secondry T3cDM). In our study nearly 80 % of all the pancreatic cancer patients had DM/prediabetes and it was of new-onset (less than 2 years before the cancer diagnosis) in 73 % out of them. We have measured the current marker of PAC (CA 19-9) together with serum microRNA-196 and -200 (that we have chosen in the previous pilot study). All the markers were significantly elevated in the pancreatic cancer patients, without any difference between the subgroups according to DM presence/absence. While the sensitivity of CA 19-9 alone (to detect the cancer) was 85 % (specificity 73 %), combining all the three markers improved it to 95 % (specificity 77 %). In the pancreatic cancer group, there were only six patients with T1 or T2 stage (others had an advanced stage of the disease - T3, T4). While CA 19-9 alone identified only 2 patients of them, the combined test identified all the six patients (data not shown in the poster). (more…)
Author Interviews, Nature, Pancreatic / 09.09.2016

MedicalResearch.com Interview with: Armando E. del Río Hernández, PhD European Research Council Fellow Head, Cellular and Molecular Biomechanics Laboratory http://biomechanicalregulation-lab.org/ Senior Lecturer, Department of Bioengineering Imperial College London MedicalResearch.com: What is the background for this study? What are the main findings? Response: Pancreatic cancer is an extremely aggressive disease with an unacceptably low survival rate that has not changed during the last 40 years despite significant efforts aimed at developing therapies against cancer cells. Pancreatic cancer is characterised by an extensive desmoplasia, which forms the majority of the tissue around the tumour. This desmoplastic tissue is known to help the tumour to grow and metastasize, and hinders drug delivery. We have focused our efforts on understanding how pancreatic stellate cells (PSCs), which are the key effectors that orchestrate the desmoplastic reaction in pancreatic cancer, can promote tumour progression. PSCs in healthy pancreas have abundant vitamin A storage in their cytoplasm and exist in a quiescent state that guarantees a balanced tissue homeostasis. In pancreatic cancer, loss of this balance activates PSCs, which lose the vitamin A content and remodel the surrounding tissue to make it favourable for cancer cell invasion. We found that treating PSCs which ATRA (All trans-retinoic acid), the active metabolite of vitamin A mechanically reprograms PSCs to promote quiescence in vitro. Quiescent PSCs are unable to remodel the microenvironment to allow pancreatic cancer cell invasion. To get more information about our findings please find the article in the open access journal Nature Communications:http://www.nature.com/articles/ncomms12630 (more…)
Author Interviews, Cancer Research, Chemotherapy, Johns Hopkins, Pancreatic / 11.08.2016

MedicalResearch.com Interview with: Rajesh Kumar NV, Ph.D. Instructor of Oncology and Pathology Johns Hopkins University School of Medicine Baltimore, MD, USA Current Affiliation: Senior Manager, Human Therapeutics Division, Intrexon Corporation, 20358 Seneca Meadows Parkway, Germantown, MD, USA MedicalResearch.com: What is the background for this study? Response: Pancreatic cancer remains as one of the most deadly malignancies in the world. Recently, a cremophor-free and albumin-bound formulation of paclitaxel (nab-PTX, Abraxane) in combination with gemcitabine (GEM, Gemzar) is recently approved as a standard of care treatment option for patients with metastatic pancreatic cancer. Majority of the newly diagnosed pancreatic cancer patients use the nab-PTX plus GEM regimen. Currently there are over 100 clinical trials at various stages with this regimen as a backbone to approved medicines or investigational agents. Since widely available cremophor-based paclitaxel (PTX, Taxol) is a key chemotherapy component for the treatment of several human malignancies and the treatment cost of nab-PTX is relatively higher than PTX, patients, clinicians, third party payers and regulatory agencies have a substantial interest in understanding whether these two drugs provide a similar level of therapeutic efficacy in pancreatic cancer. We utilized orthotopic models of human pancreatic cancer, which were shown to better recapitulate the histologic and metastatic characteristics of disease, and compared the anticancer efficacy, effect on tumor stroma modulation, metastatic spreading to distant organs and survival following GEM, PTX, nab-PTX and combinations of GEM plus PTX or nab-PTX. The preclinical trial used a total of 300 mice with established orthotopic pancreatic tumors. The tumors used for implantation were originally resected from the primary tumors of patients with moderately differentiated and poorly differentiated pancreatic cancer. (more…)
Author Interviews, Pancreatic / 27.07.2016

MedicalResearch.com Interview with: Dr-Dewi-VernereyDewi Vernerey PhD Epidemiologist / Statistician Methodology and quality of Life in oncology unit University Hospital of Besançon MedicalResearch.com: What is the background for this study? Response: The management of locally advanced pancreatic cancer (LAPC) patients is still controversial. Better discrimination for the prediction of overall survival (OS) at diagnosis is needed. Currently, there is a lack of a staging system and an absence of a consensus regarding patient-specific risk profile for OS that can lead to confusion about the development of research strategy and to potentially inappropriate management of patients with locally advanced pancreatic cancer. (more…)
Author Interviews, Brigham & Women's - Harvard, Pancreatic, Weight Research / 10.07.2016

MedicalResearch.com Interview with; Dr. Rakesh K. Jain, PhD A.W.Cook Professor of Radiation Oncology (Tumor Biology) Director, E.L. Steele Laboratory Department of Radiation Oncology Harvard Medical School and Massachusetts General Hospital Boston, MA 02114 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death worldwide, and more than half of patients diagnosed with PDAC are overweight or obese. Among patients with PDAC, obesity more than doubles the already high risk of death, and our work aims to reveal the underlying mechanisms. Specifically, we identified that obesity increases desmoplasia – an accumulation of connective tissue and inflammation – hallmark of Pancreatic ductal adenocarcinoma and discovered underlying mechanisms. In our report published online in Cancer Discovery, we describe how interactions among fat cells, immune cells and connective tissue cells in obese individuals create a microenvironment that promotes tumor progression while diminishing the response to chemotherapy. We demonstrated the negative impact of obesity on numerous aspects of tumor growth, progression and treatment response in several animal models of pancreatic ductal adenocarcinoma and confirmed some of our findings in samples from cancer patients. Along with finding that tumors from obese mice or patients exhibited elevated levels of adipocytes or fat cells and of desmoplasia, both of which fuel tumor progression and interfere with treatment response, we identified the underlying causes. The elevated desmoplasia in obese mouse models of PDAC was caused by the activation of pancreatic stellate cells through the angiotensin II type-1 receptor (AT1) signaling pathway. This activation was induced by interleukin-1 beta (IL-1ß) produced by fat cells as well as the immune cells called neutrophils within tumors. Inhibiting AT1 signaling with losartan, which is used clinically to treat hypertension, or the blockade of IL-1ß reduced obesity-associated desmoplasia and tumor growth and increased the response to chemotherapy in the obese mouse model but not in normal weight animals. Analysis of tumors from human PDAC patients revealed increased desmoplasia and fat deposits in samples from obese patients, and data from more than 300 patients showed that excess weight was associated with a reduction in patients. (more…)
Author Interviews, Nature, NYU, Pancreatic / 22.04.2016

MedicalResearch.com Interview with: Dr. George Miller, MD Vice Chair for research, Department of Surgery Associate Professor, Department of Surgery Associate Professor, Department of Cell Biology NYU Langone’s Perlmutter Cancer Center MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Miller: Cancer cell death is the goal of most therapeutic programs. Indeed, chemotherapy induces cancer cell death. We show that a novel form of cancer cell death entailing organized necrosis is a prominent way by which cancer cells die. However, paradoxically this form of cell death termed "necroptosis" actually accelerates pancreatic cancer growth in animals by inducing immune suppressive inflammation. MedicalResearch.com: What should clinicians and patients take away from your report? Dr. Miller: Novel agents are needed to block necroptosis in pancreatic cancer. This can potentially enhance the immune system's ability to fight the cancer. (more…)
Author Interviews, Chemotherapy, Pancreatic, Vanderbilt / 07.03.2016

MedicalResearch.com Interview with: Alexander A. Parikh, M.D., M.P.H. Associate Professor of Surgery Director of Hepatobiliary, Pancreatic and GI Surgical Oncology Director, Vanderbilt Pancreas Center Vanderbilt University Medical Center Nashville, TN MedicalResearch.com: What is the background for this study? Dr. Parikh: Although adjuvant chemotherapy has been proven to increase survival after successful resection of pancreatic cancer and has become the standard of care worldwide, the use of adjuvant chemoradiation is more controversial. The vast majority of randomized trials have failed to show a significant improvement in survival with the use of chemoradiation after pancreatic cancer resection. Furthermore, our own report from the multi-institutional Central Pancreatic Consortium (CPC) published several years ago failed to show a benefit in the use of chemoradiation except in high-risk groups such as lymph node positive disease. The purpose of the current study was to investigate the patterns of recurrence with the use of adjuvant chemotherapy or chemoradiation in hopes of explaining some of these differences. It was our hypothesis that systemic chemotherapy would prevent distant recurrence (and perhaps local) while chemoradiation would only prevent local recurrence and thereby have less impact on overall survival. MedicalResearch.com: What are the main findings? Dr. Parikh: The main findings demonstrated that adjuvant chemotherapy led to an improvement in both local and distant recurrence with a corresponding improvement in overall survival while chemoradiation only led to an improvement in local recurrence but not distant nor overall survival. (more…)
AACR, Author Interviews, Breast Cancer, Cancer Research, Pancreatic, Weight Research / 13.02.2016

MedicalResearch.com Interview with: Joao Incio, MD Edwin L. Steele Laboratory for Tumor Biology Massachusetts General Hospital | Harvard Medical School | Boston, MA, U.S.A Department of Internal Medicine | Hospital S. Joao | Porto, Portugal  Medical Research: What is the background for this study? What are the main findings? Dr. Incio:  The study focused on the effects of obesity on pancreatic and breast cancer, since more than half of those diagnosed with such tumors are overweight or obese. In addition, a number of large-scale studies have found that obesity leads to an increased risk of death in pancreatic, breast and other types of cancer. But prior to the current study the mechanism of obesity-induced pancreatic and breast cancer progression was unclear. We have uncovered a novel mechanism behind the ability of obesity to promote cancer progression.  We found an association between obesity and an overabundance of a factor called PlGF (placental growth factor) and that PlGF’s binding to its receptor VEGFR-1, which is expressed on immune cells within tumors, promotes tumor progression. We found that obesity increased infiltration of tumor-promoting immune cells and the growth and metastasis of pancreatic cancers. Blocking VEGFR-1 signaling shifted the immune environment towards prevention of tumor progression in obese but not in lean mice in both pancreatic and breast cancer models. We also found that PlGF was present in excess in obesity and that reduction of PlGF produced similar results to VEGFR-1 inhibition in the tumors of obese mice. We also discovered that targeting the PlGF/VEGFR-1 interaction prevents weight gain in a genetically obese mouse model but worsens a diabetes-like condition, a worsening that was alleviated by use of the common diabetes drug metformin, which also had beneficial anti-tumor effects. Our findings in cellular and animal models, as well as in patient tumor samples, indicate that targeting the PlGF/ VEGFR-1 pathway may be particularly effective in obese patients. (more…)