Author Interviews, Baylor College of Medicine Houston, Biomarkers, Brain Cancer - Brain Tumors, Cancer Research, PNAS / 19.07.2017

MedicalResearch.com Interview with: [caption id="attachment_36010" align="alignleft" width="199"]Chonghui Cheng, M.D., Ph.D. Associate Professor Department of Molecular & Human Genetics Lester & Sue Smith Breast Center Baylor College of Medicine Houston, TX77030 Dr. Cheng[/caption] Chonghui Cheng, M.D., Ph.D. Associate Professor Department of Molecular & Human Genetics Lester & Sue Smith Breast Center Baylor College of Medicine Houston, TX77030 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Understanding the mechanisms that give cancer cells the ability to survive and grow opens the possibility of developing improved treatments to control or cure disease. In the case of glioblastoma multiforme, the deadliest type of brain cancer, abnormal EGFR signaling is frequently observed. Treatment with the EGFR inhibitor erlotinib attempts to kill cancer cells. However, the clinical benefit of treatment with this and other EGFR inhibitors has been limited by the development of drug resistance. Scientists at Baylor College of Medicine discovered that the molecule CD44s seems to give cancer cells a survival advantage. Eliminating this advantage by reducing the amount of CD44s resulted in cancer cells being more sensitive to the deadly effects of the drug erlotinib.
Author Interviews, Cancer Research, Genetic Research / 22.06.2017

MedicalResearch.com Interview with: [caption id="attachment_35386" align="alignleft" width="129"]Antonis Antoniou PhD Reader in Cancer Risk Prediction Academic Course Director MPhil in Epidemiology Centre for Cancer Genetic Epidemiology Department of Public Health and Primary Care Strangeways Research Laboratory Cambridge University of Cambridge Dr. Antoniou[/caption] Antonis Antoniou PhD Reader in Cancer Risk Prediction Academic Course Director MPhil in Epidemiology Centre for Cancer Genetic Epidemiology Department of Public Health and Primary Care Strangeways Research Laboratory Cambridge University of Cambridge MedicalResearch.com: What is the background for this study? What are the main findings? Response: Several studies demonstrated that women with genetic faults in the BRCA1 and BRCA2 genes are at increased risk of developing breast and ovarian cancer. Having accurate age-specific cancer risk estimates for women with mutations is essential for their optimal clinical management. Most studies to date that estimated cancer risks for BRCA1 and BRCA2 mutation carriers have been "retrospective", in other words they look at what happened in the past. Estimates from such studies are prone to biases because they rely on the experience of women who have already developed cancer and on self-reported cancer family history information on relatives - which may have inaccuracies. The ideal epidemiological study design for estimating cancer risks are prospective studies.  In prospective studies, healthy women with genetic faults are followed over time and overcome these potential biases. However, to date, published  prospective studies have been very small. In the present study we used data from a prospective cohort of women with BRCA1 and BRCA2 mutations who were recruited from 1997 to 2011 and were followed over time. The study included almost 10,000 women who were included in the analyses, and was made possible through collaborations between scientists from Europe, North America and Australia.  The prospective study design explains why it has taken 20 years of hard work to get these results. Most importantly, it took an enormous long-term contribution and commitment from the women themselves to allow the scientists to be able to assemble this dataset. Here, we were able to estimate more precisely the breast and ovarian cancer risks for women with faults in BRCA1 and BRCA2.  These risk estimates will provide more confidence in the counseling and clinical management of women with faults in the BRCA1 and BRCA2  genes. A novel finding in this study is that breast cancer risk for women with faults in BRCA1 and BRCA2  increases rapidly at a young age then remains at a constant high level for the rest of their lives. It peaks in the 40’s for BRCA1 mutation carriers and in the 50’s for BRCA2 carriers, but  carriers of mutations in both genes  are at about the same high risk in later life. This is important information to inform the clinical management of older mutation carriers. This study also shows clearly that for women with a mutation, there are other factors that are important in modifying the breast cancer risk. The study has demonstrated that the extent of the woman’ family history of cancer and the exact place on the gene where her mutation is located are very important in determining the actual risk.
ASCO, Author Interviews, Cancer Research, Vaccine Studies / 12.06.2017

MedicalResearch.com Interview with: Chrisann Kyi, MD Fellow, Division of Hematology and Medical Oncology Icahn School of Medicine at Mount Sinai One Gustave L. Levy Place, Box 1079 New York, NY 10029 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Mutation-derived tumor antigens (MTAs or neoantigens) arise as a direct result of somatic mutations, including nucleotide substitutions, insertions, and deletions that occur during carcinogenesis. These somatic variations can be characterized via genetic sequencing and used to identify MTAs with predictive computational genomics and algorithms. To be a good candidate for a cancer vaccine, a mutated cancer protein must be visible and recognized by T cells, the soldiers of the immune system, so that they in turn can be educated to seek out and destroy cancer cells that bear the mutated protein. At annual ASCO conference this year, we are presenting an exciting clinical trial investigating the feasibility, safety, and immunogenicity of a personalized MTA-based multi-peptide vaccine in the adjuvant treatment for multiple solid tumors. In this trial, the patient’s own tumor is used to manufacture a cancer vaccine according to the mutations in their individual tumor. This vaccine is then given back to the patient in the adjuvant setting. The clinical trial is currently open and accruing at Tisch Cancer Center at Mount Sinai Hospital, NY
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.
Author Interviews, Biomarkers, Genetic Research, Lung Cancer / 25.04.2017

MedicalResearch.com Interview with: Hestia Mellert, PhD Director, Molecular Product Development Biodesix: Making Medicine Personal Boulder, CO MedicalResearch.com: What is the background for this study? What are the main findings? Response: Identifying specific genetic mutations in non-small cell lung cancer patients helps clinicians choose the best treatment options; specific therapies that target mutations can improve patient outcomes, including reducing the risk of death or lessening the severity of the disease. However, nearly 80% of cancer patients do not have genetic mutation results available at initial oncology consultation; up to 25% of patients begin treatment before receiving their results. These factors hinder physicians’ ability to pursue optimal treatment strategies. This study found that a blood-based assay, the GeneStrat test, provides results in 72 hours for 94% of patients, which expands testing options, and supports faster treatment decisions by physicians.
Author Interviews, Biomarkers, Cancer Research / 24.04.2017

MedicalResearch.com Interview with: [caption id="attachment_34117" align="alignleft" width="112"]Thurai Moorthy Ph.D.</strong> President, MultiGEN Diagnostics Greensboro, NC 27405 Dr. Moorthy[/caption] Thurai Moorthy Ph.D. President, MultiGEN Diagnostics Greensboro, NC 27405 MedicalResearch.com: What is the background for this study? Response: As more cancer related genetic markers are reported, there is a need for appropriate molecular tests to meet clinical expectations. These expectations include detection at very low amount in a heterogeneous cell population, such as Formalin Fixed Paraffin embedded (FFPE) tumor biopsies. Braf p.V600E/K mutations are cancer-specific markers found in a variety of cancers. There are several drugs in use, and more drugs are being developed, which are prescribed only to those patients whose tumor carries either of these (Braf p.V600E/K) mutations. Hence, detection of Braf p. V600E/K is critical in the treatment of cancer patients. In this regard, we developed a new platform technology, Allele Specific Multiplex Sequencing (ASMS, for the detection of cancer markers from biopsy samples. As a demonstration project, we tested the new platform technology for the detection of Braf p.V600E/K using tumor samples (FFPE) previously tested by two presently used methods.
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.
Author Interviews, Cancer Research, JAMA, Vitamin D / 27.03.2017

MedicalResearch.com Interview with: [caption id="attachment_33384" align="alignleft" width="75"]Joan M. Lappe, Ph.D., R.N., F.A.A.N. Associate Dean for Research, College of Nursing Criss/Beirne Professor of Nursing Professor of Medicine Creighton University Omaha NE 68131 Dr. Lappe[/caption] Joan M. Lappe, Ph.D., R.N., F.A.A.N. Associate Dean for Research, College of Nursing Criss/Beirne Professor of Nursing Professor of Medicine Creighton University Omaha NE 68131 MedicalResearch.com: What is the background for this study? What are the main findings?
  • Numerous observational studies show that higher vitamin D intake and serum 25, hydroxyvitamin D [25(OH)D], the functional indicator of vitamin D status, are associated with lower incidence of cancer.
  • However, the scientific fields consider randomized clinical trials (RCT) as a gold standard for testing new interventions for prevention and treatment of disease. In the only RCT of cancer and vitamin D to date with cancer as a primary outcome, the Women’s Health Initiative, postmenopausal women randomly assigned to vitamin D3400 IU/day and calcium 1000 mg/day showed no difference from those assigned to placebo in colorectal cancer incidence. One criticism of that study was that the vitamin D intervention was low, only 400 international units (IU) per day.
  • In our study we found that, in healthy women ages 55 and older with a mean baseline serum 25(OH)D of 33 ng/mL, supplementation with 2000 IU/day of vitamin D3and 1500 mg/day of calcium for four years, compared with placebo, decreased all-type cancer incidence by about 30%, but this did not reach statistical significance. (p value =0.057 and for statistical significance, the p value would need to be less than 0.05.)
  • In a secondary analysis, we re-analyzed the data excluding cancers that developed during the first year of study and were likely present but not diagnosed upon study enrollment. The findings here were that vitamin D and calcium did significantly decrease cancer risk by about 35%.
  • In another secondary analyses, we combined all of the serum 25(OH)D values to determine if higher levels were associated with lower cancer incidence. Here, higher serum 25(OH)D was significantly associated with lower cancer incidence. Persons with serum 25(OH)D of 55 ng/mL had a 35% lower risk of cancer than persons with serum 25(OH)D of 30 ng/mL.  This is especially interesting since current recommendations for sufficient serum 25(OH)D levels are 20 ng/mL (the National Academy of Medicine) and 30 ng/mL (the Endocrine Society).
  • Note that serum 25(OH)D is a better predictor of cancer development than assigning persons to supplement groups. Serum 25(OH)D takes into account poor compliance of the active supplement group with taking supplements, personal use of supplements by the placebo group, dietary vitamin D intake, sunlight exposure, and the variation among persons in absorption and metabolism of the vitamin D supplement.
Author Interviews, Cancer Research, Immunotherapy, JAMA / 12.02.2017

MedicalResearch.com Interview with: [caption id="attachment_31946" align="alignleft" width="96"]Michael C. Heinrich, MD Professor of Medicine and Cell and Developmental Biology Oregon Health & Sciences University Dr. Michael Heinrich[/caption] Michael C. Heinrich, MD Professor of Medicine and Cell and Developmental Biology Oregon Health & Sciences University MedicalResearch.com: What is the background for this study? What are the main findings? Response: Prior to 2000, there were no effective medical treatments for advanced GI stromal tumor and patients faced an average life expectancy of 18 months or less.  In our study of the  long-term treatment results using imatinib (Gleevec),  we found that approximately 7% of patients were still on front-line therapy at 10 years without any evidence of tumor progression.  More importantly, the estimated 10 year survival was 23%.   Progression-free and overall survival rates were significantly higher for patients with KIT exon 11-mutant GIST when compared with patients with KIT exon 9-mutant or “wild-type” GIST (no KIT/PDGFRA mutations).
Author Interviews, Cancer Research, Technology / 01.02.2017

MedicalResearch.com Interview with: [caption id="attachment_31687" align="alignleft" width="186"]Vasileios Vavourakis Marie Skłodowska-Curie Fellow Centre for Medical Image Computing Department of Medical Physics & Biomedical Engineering Front Engineering Building, Malet Place University College London WC1E 6BT, London, UK Vasileios Vavourakis[/caption] Vasileios Vavourakis Marie Skłodowska-Curie Fellow Centre for Medical Image Computing Department of Medical Physics & Biomedical Engineering Front Engineering Building, Malet Place University College London WC1E 6BT, London, UK  MedicalResearch.com: What is the background for this study? What are the main findings? Response: It is already known that chemical factors play an important role in pathological angiogenesis, the process whereby cancer induces the formation of new blood vessels to provide it with nutrients. However, there is little knowledge about how mechanical forces induced by tumour growth affect the development and functionality of this pathological vasculature. By developing a mathematical & computational model – also referred in the research community as in-silico model – of the physical and chemical interactions occurring during angiogenic cancerous growth, we aimed to provide insights about how mechanical forces influence cancer-induced angiogenesis. The most important finding of our study is that mechanical forces play a key role in solid tumour-induced angiogenesis.
Author Interviews, Cancer Research, Diabetes, Pharmacology, Science / 05.01.2017

MedicalResearch.com Interview with: Dr. Don Gary Benjamin Biozentrum, University of Basel Basel, Switzerland. MedicalResearch.com: What is the background for this study? What are the main findings? Response: We initiated the study to find a co-drug that would increase the anti-cancer effect of the commonly prescribed anti-diabetic drug metformin. Metformin is a very well tolerated medication, however the dosage required to show anti-cancer activity is higher than that usually prescribed, hence the aim of the study. We found that metformin in combination with a second drug, syrosingopine (an anti-hypertensive), potently kills cancer cells in a variety of pre-clinical models. Quite nicely, both these drugs combine to kill the cells at a concentration where they have no impact on cell growth when applied singly.
Author Interviews, Cancer Research, Nature / 01.12.2016

MedicalResearch.com Interview with: [caption id="attachment_30081" align="alignleft" width="150"]Sudarshan Anand, PhD Department of Cell, Developmental and Cancer Biology Department of Radiation Medicine Oregon Health and Science University Portland, Oregon Dr. Sudarshan Anand[/caption] Sudarshan Anand, PhD Department of Cell, Developmental and Cancer Biology Department of Radiation Medicine Oregon Health and Science University Portland, Oregon MedicalResearch.com: What is the background for this study? What are the main findings? Response: Almost half of all cancer patients receive radiation therapy during the course of their disease. While the impact of radiation on the cancer cells has been well studied in experimental models, its effects on the accessory cells that are present in the tumor are not well known. One of the major interests of our lab is studying these accessory cells of the tumor aka “the tumor microenvironment”. These group of cells consists of blood vessel cells, fibroblasts and immune cells that are normal cells that have been recruited by the tumor and generally support tumor growth. The goal of this study was to understand the impact of radiation (and broadly DNA damaging agents) on the blood vessel cells in the tumor. We focused on a specific type of molecule called microRNAs (miRs) in these cells. miRs are small RNA molecules that bind to dozens of messenger RNAs and the production of proteins. We discovered a group of microRNAs that was induced in blood vessel cells by radiation, a chemotherapy agent cisplatin and peroxide an agent that mimics oxidative stress that is often present in cancers. We found that the top candidate on this list was a microRNA that mimicked radiation by inducing DNA damage and eventually killing the blood vessel cells. Administering this microRNA, either within a tumor or using a specific nanoparticle that delivers cargo to the tumor blood vessels, decreased tumor growth in mouse models of breast cancer, brain cancer and colorectal cancer. We found that the efficacy of this agent was a result of its ability to suppress a protein TREX1, that is often mutated in human lupus. In other words, this microRNA was able to create some of the immune and inflammatory features of lupus within a tumor and induce proteins that triggered cell death on tumor cells. Overall, our work illustrates how the tumor accessory cells respond to radiation and highlights the cross-talk between different accessory cells and the tumor cells.
Author Interviews, Cancer Research, Chemotherapy / 27.11.2016

MedicalResearch.com Interview with: [caption id="attachment_29986" align="alignleft" width="150"]Kelvin K. Tsai, MD, PhD Associate Investigator and Attending Physician Laboratories for Tumor Aggressiveness and Stemness National Institute of Cancer Research, National Health Research Institutes Associate Professor and Principal Investigator Laboratories of Advanced Molecular Therapeutics Graduate Institute of Clinical Medicine College of Medicine, Taipei Medical University, Taiwan Dr. Kelvin K. Tsai[/caption] Kelvin K. Tsai, MD, PhD Associate Investigator and Attending Physician Laboratories for Tumor Aggressiveness and Stemness National Institute of Cancer Research, National Health Research Institutes Associate Professor and Principal Investigator Laboratories of Advanced Molecular Therapeutics Graduate Institute of Clinical Medicine College of Medicine, Taipei Medical University, Taiwan MedicalResearch.com: What is the background for this study? Response: Human cancer is a complex organ consisting of a heterogenous collection of cancer cells and stroma cells. Many solid tumors such as breast cancer and pancreatic cancer are characterized by a pronounced stromal fibrosis termed desmoplasia. Studies showed that systemic chemotherapy can target not only cancer cells but also the stromal fibroblasts, which may have significant impacts on the treatment response in desmoplastic cancers. We set out to study whether and how traditional “maximum tolerated dose (MTD)” chemotherapy affects the tumor fibroblasts and thereby modulates the treatment response, and if so how this therapy-induced stroma perturbation can be avoided or attenuated.
Author Interviews, Cancer Research, Immunotherapy / 17.11.2016

MEDICALRESEARCH.COM INTERVIEW WITH: [caption id="attachment_29733" align="alignleft" width="160"]THOMAS W. DUBENSKY, JR., PH.D.</strong> CHIEF SCIENTIFIC OFFICER ADURO BIOTECH, INC. DR. THOMAS W. DUBENSKY, Jr.[/caption] THOMAS W. DUBENSKY, JR., PH.D. CHIEF SCIENTIFIC OFFICER ADURO BIOTECH, INC. MedicalResearch.com: What is the background for this study? What are the main findings? Response: This presentation highlights findings from multiple preclinical models evaluating ADU-S100 (also known as MIW815), Aduro Biotech’s investigational STING (Stimulator of Interferon Genes) Pathway Activator immunotherapy. The company is developing ADU-S100 in partnership with Novartis. ADU-S100 is a synthetic ‘off-the-shelf’ small molecule immune modulator that is designed to generate a response against a patient’s own unique set of cancer antigens. It does this through the activation of human STING. STING is generally expressed at high levels in immune cells, including dendritic cells. Once activated, the STING receptor initiates a profound innate immune response through multiple pathways, inducing the expression of a broad profile of cytokines, including interferons and chemokines. This subsequently leads to the development of a systemic tumor antigen-specific T-cell adaptive immune response. We conducted preclinical studies in a variety of preclinical models to better understand the potential mechanism of action of ADU-S100 and its potential for treating a variety of cancer types, both within the immediate tumor environment, as well as throughout the body. Data from these preclinical studies suggest the following:
  • Intratumoral injection of ADU-S100 activates the STING Pathway and induces both a durable local and systemic anti-tumor immune response as evidenced by induction of type I interferons (IFNs) and a CD8+ T-cell response.
  • ADU-S100 is able to induce tumor-specific memory mediated by immune cells (e.g. T-cells and NK-cells) whereby the immune system is able to eliminate specific cancerous cells upon their reintroduction without further therapy.
  • Combination of STING activation in the tumor microenvironment and an anti-PD-1 checkpoint inhibitor enhances antitumor efficacy activation of the STING pathway, resulting in the complete eradication of local and distal tumors.
Author Interviews, Cancer Research, Immunotherapy / 11.11.2016

MedicalResearch.com Interview with: [caption id="attachment_29564" align="alignleft" width="75"]Dr. Michael Lotze, MD Chief Scientific Officer, Lion Biotechnologies San Carlos, CA 94070 Dr. Lotze[/caption] Dr. Michael Lotze, MD Chief Scientific Officer, Lion Biotechnologies San Carlos, CA 94070 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Adoptive cell therapy (ACT) with Tumor-infiltrating Lymphocytes (TIL) has shown promise in mediating cancer regression which rely on activation in vivo compared to other immunotherapies that utilize genetically modified T-cells. In TIL therapy, autologous administration of TIL expanded outside the body elicits a highly individualized, specific and potent attack against the tumor. Clinical trials conducted at the National Cancer Institute evaluating TIL therapy for the treatment of metastatic melanoma reported overall response rates of up to 56%. The durable responses observed in these metastatic melanoma patients as well as other patients with cervical cancer, cholangiocarcinoma, and head and neck cancer signal the potential for broader application of TIL therapy to treat patients with other solid tumors, currently an area of substantial unmet clinical need. Lion’s study, recently presented at the Society for Immunotherapy of Cancer, sought to demonstrate the feasibility of culturing and expanding TIL isolated from non-melanoma tumors. We were successful in culturing TIL from tumors obtained from bladder, cervical, head and neck, lung and triple negative breast cancer.
Author Interviews, Cancer Research, Immunotherapy, Vaccine Studies / 09.11.2016

MedicalResearch.com Interview with: Leslie Chong Imugene Chief Operating Officer Armadale, Australia Leslie Chong Imugene Chief Operating Officer Armadale, Australia   MedicalResearch.com: What is the background for this study? How does HER-Vaxx work? • The technology originates from the Medical University of Vienna, one of Europe’s leading cancer institutes and was identified in 2012 by Dr Axel Hoos (Currently Sr. Vice President of Oncology R&D at GlaxoSmithKline, previous Clinical Lead on Ipilumimab at Bristol-Myers Squibb, a director at Imugene; his only Board seat worldwide) • HER-Vaxx is a peptide vaccine designed to treat tumours that over-express the HER2/neu receptor, such as gastric, breast, ovarian, lung and pancreatic cancers. The vaccine is constructed from various B Cell epitopes of HER2/neu. It has been shown in pre-clinical work and in a Phase 1 study to stimulate a potent polyclonal antibody response to HER2/neu, a commercially and clinically validated cancer target. HER-Vaxx’s successful Phase 1 study was in patients with metastatic breast cancer and the next stage of development will be a Phase 1b/2 study in patients with gastric cancer initiating in 2016.
Author Interviews, Cancer Research, Pharmacology / 17.10.2016

MedicalResearch.com Interview with: [caption id="attachment_28926" align="alignleft" width="150"]Dr Pan Pantziarka, PhD Scientist: Anticancer Fund (www.anticancerfund.org) Coordinator: Repurposing Drugs in Oncology (www.redo-project.org) Dr Pan Pantziarka[/caption] Dr Pan Pantziarka, PhD Scientist: Anticancer Fund (www.anticancerfund.org) Coordinator: Repurposing Drugs in Oncology (www.redo-project.org) MedicalResearch.com: What is the background for this study? What are the main findings? Response: This study is part of the Repurposing Drugs in Oncology (ReDO) project to look at a series of non-cancer drugs which have strong evidence of anti-cancer effects. Other drugs have included the antacid cimetidine, the antibiotic clarithromycin and the NSAID diclofenac. The data for propranolol comes from multiple sources: epidemiological data and retrospective data from cancer patients who have also been treated concurrently with propranolol, pre-clinical work in vitro and in animal models and from case series reports in which cancer patients have had propranolol added to their existing treatments. The main findings are that propranolol has multiple mechanisms of action, including anti-proliferative and immunomodulation. There is particularly strong evidence that shows that propranolol has potent effects in the treatment of the rare soft-tissue sarcoma angiosarcoma. It is also suggested that when used at the time of surgery, propranolol in combination with a COX-2 inhibitor, can reduce the risk of metastatic spread.
Author Interviews, Cancer Research, Immunotherapy / 11.10.2016

MedicalResearch.com Interview with: [caption id="attachment_28818" align="alignleft" width="200"]Bernard Vanhove, Chief Operating Officer Director of R&D and International Scientific Collaborations Ose Immunotherapeutics Bernard Vanhove[/caption] Bernard Vanhove, Chief Operating Officer Director of R&D and International Scientific Collaborations Ose Immunotherapeutics MedicalResearch.com: What is the background for this study? What are the main findings? Response: Myeloid suppressive cells, including tumor associated macrophages (TAM) and myeloid-derived suppressor cells (MDSC), represent an abundant immune cell type in the microenvironment of solid tumors where they promote tumor growth, metastases, angiogenesis, inhibiting anti-tumor immune responses. Myeloid cells selectively express SIRPα, an immune tyrosine associated inhibitory receptor (also named CD172a), which controls myeloid functions. We investigated the role of Effi-DEM, new generation checkpoint inhibitor specifically targeting the SIRP- α receptor on the strategic SIRP-α/CD47 pathway in human macrophages polarization and MDSC differentiation. CD47 the ligand of SIRP alpha is ubiquitously expressed in human cells and has been found to be overexpressed in many different tumor cells with a poor prognosis established. Effi-DEM is a selective antagonist of these myeloid suppressive cells as its target SIRP-α is expressed on these cells. Based on this rationale, the preclinical studies conducted with Effi-DEM have demonstrated its potential to transform suppressor myeloid and tumor associated macrophage cells in non-suppressive cells, thereby inducing a reactivation of the immune response. Effi-DEM has also shown to be effective in various aggressive cancer models with encouraging preclinical results, both in monotherapy and in therapeutic combinations with anti-PD-L1 (checkpoint inhibitors) and anti-CD137 (4-1BB) mAbs, activators of the T-cell response. Significant efficacy and survival increase data were demonstrated in models of hepatocarcinoma, melanoma and triple negative breast cancer.
AACR, Author Interviews, Cancer Research / 21.09.2016

MedicalResearch.com Interview with: [caption id="attachment_28144" align="alignleft" width="150"]Nancy Davidson, MD President of the American Association for Cancer Research (AACR) and Director, University of Pittsburgh Cancer Institute Dr. Nancy Davidson[/caption] Nancy Davidson, MD President of the American Association for Cancer Research (AACR) and Director,  Cancer Institute University of Pittsburgh Dr. Davidson discusses the 2016 AACR Cancer Progress Report. “The report serves as an educational document for both Congress and the public, alike. The report is a call to action, designed to urge Congress and the American public to stand firm in their commitment to the conquest of cancer”. MedicalResearch.com: What is the background and goals for this report? Dr. Davidson:
  • This is the sixth edition of our annual Cancer Progress Report.
  •  The annual report is the cornerstone of the AACR’s educational and advocacy efforts:
  • The report outlines efforts to increase public and Congressional understanding of cancer and the importance of cancer research to public health and
  • Efforts to advocate for increased federal funding for the NIH, NCI, FDA, and other federal agencies that are vital for fueling progress against cancer
  • The first report was written in 2011, the year that marked the 40th anniversary of the signing of the National Cancer Act of 1971, to commemorate the advances in cancer research that had been made to date and to paint a picture of where the science was leading us.
Author Interviews, Biomarkers, Cancer Research, Lung Cancer / 11.09.2016

MedicalResearch.com Interview with: [caption id="attachment_27803" align="alignleft" width="200"]Karen L. Reckamp, M.D. Associate Professor City of Hope Comprehensive Cancer Center Duarte, CA 91010 Dr. Karen Reckamp[/caption] Karen L. Reckamp, M.D. Associate Professor City of Hope Comprehensive Cancer Center Duarte, CA 91010 MedicalResearch.com: What is the background for this study? What are the main findings? Response: • Approximately 60% of patients with non-small cell lung cancer (NSCLC) receiving EGFR tyrosine kinase inhibitors (TKIs) will develop TKI resistance through the acquisition of the EGFR T790M mutation. • A major challenge for assessing EGFR mutation status in advanced NSCLC is the availability of suitable biopsy tissue for molecular testing, specifically for determination of the emergence of T790M following progression on initial EGFR TKI therapy. • The objective of this study was to demonstrate that a highly sensitive and quantitative next-generation sequencing analysis of EGFR mutations is feasible from urine and plasma, providing comparable clinical information while potentially mitigating the issues associated with tissue biopsies. • This blinded, retrospective study was conducted on matched tissue, urine and plasma specimens collected from 63 patients with Stage IIIB-IV NSCLC enrolled in the TIGER-X trial of rociletinib, an investigational 3rd generation tyrosine kinase inhibitor (TKI), targeting T790M.
ASCO, Author Interviews, Biomarkers, Personalized Medicine, UCSD / 07.06.2016

MedicalResearch.com Interview with: [caption id="attachment_24655" align="alignleft" width="200"]Maria Schwaederle PharmD Clinical Research Scientist Center for Personalized Cancer Therapy UCSD Moores Cancer Center La Jolla, CA 92093 Dr. Maria Schwaederle[/caption] Maria Schwaederle PharmD Clinical Research Scientist Center for Personalized Cancer Therapy UCSD Moores Cancer Center La Jolla, CA 92093 MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Schwaederle: We performed this analysis with experts in the field, including but not limited to Drs Schilsky, Lee, Mendelsohn and Kurzrock, all known for their experience in the area of precision/personalized medicine. Historically, phase I trials (which are often first in human or highly experimental in other ways) were believed to be examining only toxicity. Our meta-analysis of 13,203 patients shows that in the era of precision medicine, this historical belief needs to be discarded. Second, it is the use of precision medicine that makes this belief outdated. Indeed, Phase I trials that utilized a biomarker-driven approach that is the essence of precision medicine had a median response rate of about 31%, which is higher than many FDA approved drugs, and this is in spite of the fact that phase I patients are a highly refractory group having failed multiple lines of conventional therapy. Importantly, however, it was not the use of targeted agents alone that was important. It was the biomarker-based approach where patients are matched to drugs. Without matching, response rates were dismal—about 5%.
Author Interviews, Cancer Research / 05.04.2016

MedicalResearch.com Interview with: Katriina Heikkila, PhD Lecturer, London School of Hygiene and Tropical Medicine Honorary Researcher, the Finnish Institute of Occupational Health MedicalResearch.com: What is the background for this study? Dr. Heikkila:  Governments across the world have set regulations on working time, many recommending a maximum of 48- or 55-hour working week but many men and women today regularly work longer than recommended maximum hours. Working exceedingly hours is associated with many adverse health outcomes, such as an increased risk of cardiovascular disease, but the relationship of excess working hours with incident cancer has so far been unclear. To address this gap in the knowledge, we investigated the association between weekly working hours and incident cancer using individual-level data from over 116 000 initially cancer-free men and women from 12 research studies from Finland, Denmark, Sweden, Germany, the Netherlands and the UK.
Author Interviews, Cancer Research / 25.02.2016

MedicalResearch.com Interview with: [caption id="attachment_22038" align="alignleft" width="130"]Ross Cagan, PhD Professor, Developmental and Regenerative Biology, Oncological Sciences, Ophthalmology Senior Associate Dean for the Graduate School of Biomedical Sciences Icahn School of Medicine at Mount Sinai Dr. Ross Cagan[/caption] Ross Cagan, PhD Professor, Developmental and Regenerative Biology, Oncological Sciences, Ophthalmology Senior Associate Dean for the Graduate School of Biomedical Sciences Icahn School of Medicine at Mount Sinai Medical Research: What is the background for this study? What are the main findings? Dr. Cagan: Large scale screening for new cancer drugs typically rely on either cell culture or biochemical assays. These types of systems do not take into account the complexity of cancer and drug interactions at a whole animal level. We developed a whole animal screening method using Drosophila (fruit flies) as a model organism. Our model activates the Ras and PI3K oncogenic pathways specifically in lung-like Drosophila tissue. The end result is overproliferation, cell migration and animal lethality. These phenotypes were used to screen a large library of drugs, from which a number of hits were discovered. This study focused on the synergistic abilities of the Mek-inhibitor, trametinib, and a statin to rescue the cancerous phenotypes at a molecular, cellular and whole animal level.
Author Interviews, Cancer Research / 27.01.2016

[caption id="attachment_20977" align="alignleft" width="171"]Dr. Anne Burtey, PhD Department of Biomedicine, Biomaterials, Department of Clinical Dentistry and K. G. Jebsen Brain Tumour Research Center University of Bergen, Bergen, Norway; Department of Pathology and Department of Clinical Medicine Haukeland University Hospital, Bergen, Norway and NorLux Neuro-Oncology Laboratory, Department of Oncology Luxembourg Institute of Health Luxembourg, Luxembourg Dr. Anne Burtey[/caption] MedicalResearch.com Interview with: Dr. Anne Burtey, PhD Department of Biosciences University of Oslo Oslo, Norway Medical Research: What is the background for this study? Dr. Burtey: At the site of tumors, cancer cells communicate with normal cells present in the microenvironment. This communication deeply modifies these cells that become “devoted” to tumors, helping the latter in growing, in becoming more invasive. Drugs blocking this communication - or taking advantage of it to spread better within tumors and towards “tumor-helper” cells - may represent a new generation of drugs with increased anti-cancer properties. To develop such drugs, we first need to understand the communication processes at stake between cancer and normal cells. Previous reports suggested that cells communicate by trading entire subsets of components by contact- or secretion-dependent mechanisms. Whereas the latter is rather well studied, the former remains largely unclear. In 2004, our group identified tunneling nanotubes (TNTs) as a cellular feature for contact-dependent communication (Rustom et al., Science 2004). They are thin membranous bridges established between cells that facilitate the cell-to-cell transport of ions, proteins, RNAs, mitochondria and even viruses. That TNTs were observed in a variety of cells including cancer cells suggests that they may represent a general route of communication and play a role in cancer.