Addiction, Author Interviews, Cancer Research, Pharmacology / 04.07.2016
At Lower Dose, Addiction Drug Naltrexone May Have Anti-Cancer Effects
MedicalResearch.com Interview with:
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Dr. Wai Liu[/caption]
Dr Wai Liu
Senior Research Fellow
St George's University of London
London
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Naltrexone is a drug commonly used to wean addicts off alcohol and heroin, but clinical evidence has shown that when the drug is used at lower doses, patients would exhibit alter immunity. The symptoms that patients with a number of autoimmune diseases and those associated with chronic pain would ease significantly. Additionally, a number of reports showed patients with some forms of cancer would experience therapeutic benefit. Interestingly, the doses of the drug was crucial, and the non-conventional effects of naltrexone was only achieved at doses that were lower that what was conventionally used. We set about to understand why a drug could have such different effects when used at differing doses. Our results show that the genetic profile of the drug is subtly different at the two different doses, which helped us identify novel ways in which the drug could be used to induce an anticancer effect.
Dr. Wai Liu[/caption]
Dr Wai Liu
Senior Research Fellow
St George's University of London
London
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Naltrexone is a drug commonly used to wean addicts off alcohol and heroin, but clinical evidence has shown that when the drug is used at lower doses, patients would exhibit alter immunity. The symptoms that patients with a number of autoimmune diseases and those associated with chronic pain would ease significantly. Additionally, a number of reports showed patients with some forms of cancer would experience therapeutic benefit. Interestingly, the doses of the drug was crucial, and the non-conventional effects of naltrexone was only achieved at doses that were lower that what was conventionally used. We set about to understand why a drug could have such different effects when used at differing doses. Our results show that the genetic profile of the drug is subtly different at the two different doses, which helped us identify novel ways in which the drug could be used to induce an anticancer effect.










Lindsay Kohler[/caption]
Lindsay Kohler MPH
Mel and Enid Zuckerman College of Public Health
Tucson, Arizona
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Several studies have reported that following health promotion guidelines for diet, physical activity, and maintenance of a healthy body weight may reduce the risk of getting cancer or dying from cancer. We performed a systematic review to examine the associations between established cancer prevention guidelines for diet and physical activity and cancer outcomes. We found that adhering to cancer prevention guidelines set forth by the American Cancer Society or the World Cancer Research Fund/American Institute for Cancer Research consistently reduced the risk of overall cancer incidence and mortality (10-61%) in the studies included in this review. In addition, higher adherence to the guidelines consistently reduced the risk of breast, colorectal, and endometrial cancers. Adherence to a pattern of healthy behaviors may significantly reduce cancer incidence and mortality.
Prof. Peter Johnson[/caption]
Peter Johnson MA, MD, FRCP
Professor of Medical Oncology
Cancer Research UK Centre
Southampton General Hospital
Southampton
MedicalResearch.com: What is the background for this study? What are the main findings?
Prof. Johnson: Based upon retrospective series looking at the ability of interim PET to predict the outcomes of treatment, we aimed to test the idea of modulating treatment in response to an early assessment of the response to ABVD: could we safely reduce the amount of treatment by omitting bleomycin in the group who had responded well? Although the risk of severe toxicity from bleomycin is generally low, for the small number of patients who experience it, it can be life-changing or even fatal. We also wanted to test whether it might be possible to reduce the use of consolidation radiotherapy by comparison to our previous trials, and this seems to have worked too: we used radiotherapy in less than 10% of patients in RATHL, as compared to around half in our previous trials. We have seen better survival figures than in our previous studies with less treatment overall, so it feels as though we are on the right track.
Dr. Ying Bao[/caption]
Dr. Ying Bao Sc.D., M.D
Assistant Professor of Medicine
Channing Division of Network Medicine
Department of Medicine
Brigham and Women's Hospital
Harvard Medical School,
Boston, MA
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Nuts are rich in bioactive macronutrients, micronutrients, tocopherols and phytochemicals. Current epidemiological evidence has consistently linked increased nut consumption to reduced risk of several chronic conditions including cardiovascular diseases, type 2 diabetes, and inflammation. In contrast, evidence on nut consumption and cancer risk has been insufficient and equivocal.
Prostate cancer is the leading cancer among U.S. men, with approximately 220,800 new cases diagnosed in 2015. However, very few studies have investigated the association between nut intake and prostate cancer. Thus, in the current study, we followed 47,299 US men from 1986-2012, and examined
(1) whether consuming more nuts prevents getting prostate cancer, and
(2) whether consuming more nuts reduces death rates among non-metastatic prostate cancer patients.
During 26 years of follow-up, 6,810 men were diagnosed with prostate cancer, and 4,346 of these patients were without metastasis at diagnosis. We found no association between nut intake and being diagnosed with prostate cancer. However, among non-metastatic prostate cancer patients, those who consumed nuts 5 or more times per week after diagnosis had a significant 34% lower rate of overall mortality than those who consumed nuts less than once per month.
Dr. Lan Huang[/caption]
Dr. Lan Huang PhD
Co-founder, Chairman and CEO
Dr. Orit Markowitz[/caption]
Orit Markowitz, MD
Director of Pigmented Lesions and Skin Cancer
The Mount Sinai Hospital and
Assistant Professor of Dermatology
Icahn School of Medicine at Mount Sinai
Director of Pigmented lesions clinic
Brooklyn VA,
Adjunct Professor, Dermatology
SUNY Downstate Medical Center, Brooklyn, NY
Chief of Dermatology
Queens General Hospital, Jamaica, NY
MedicalResearch.com Editors’ Note: As part of an ongoing series of occasional article on cancer prevention, Dr. Markowitz from The Mount Sinai Hospital discusses skin cancer and the use Optical Coherence Tomography in skin cancer diagnosis and treatment.
MedicalResearch.com: How common is the problem of non-melanoma skin cancer? Are they difficult to detect and treat?
Dr. Markowitz: Skin cancer is the most commonly diagnosed cancer in the United States. Non melanoma skin cancers, including basal cell carcinomas and squamous cell carcinomas, are the most common malignancies of the skin, constituting around 80 percent of all skin cancers. The annual cost of treating skin cancers in the U.S. is estimated at $8.1 billion, with $3.3 billion for melanoma.
Prof. Frances Balkwill[/caption]
Professor Frances Balkwill OBE, FMedSci
Lead, Centre for Cancer and Inflammation
Barts Cancer Institute
Queen Mary University of London
London
MedicalResearch.com: What is the background for this study?
Prof. Balkwill: We wanted to find out if chemotherapy altered patients immune system especially the immune cells that co-exist with cancer cells in tumors.
We studied women with ovarian cancer who often receive chemotherapy after diagnosis but before surgery. This meant, at least in some of them, we could study a biopsy taken before treatment began and also a biopsy taken during the operation.
Dr. Petkov[/caption]
Valentina Petkov, MD, MPH
Health Scientist/Program Officer
NIH/NCI/DCCPS/Surveillance Research Program
MedicalResearch.com: What is the background for this study?
Dr. Petkov: The number of breast cancer diagnoses is increasing in older patients because of increasing life expectancy and changing population demographics. Despite high incidence, little is known about breast cancer biology and outcomes in patients older than 70, which are often under-represented in clinical trials. The 21-gene Oncotype DX Breast Recurrence Score assay has been used in clinical practice to predict distant recurrence risk and chemotherapy benefit in lymph node negative, hormonal receptor positive (estrogen and/or progesterone receptor positive) invasive breast cancer since 2004. The goal of our study was to evaluate the role of the 21 gene assay in older patients at population level.
We used Surveillance Epidemiology and End Results (SEER) data. We included in the analysis 40,134 patients who were diagnosed with invasive breast cancer between 2004 and 2011, had negative nodes and their tumors were hormonal receptor positive and HER2 negative. Breast Cancer Specific Mortality (BCSM) was assessed at 5 years after diagnosis in patients with low risk (Recurrence Score <18), intermediate risk (Recurrence Score 18-30) and high risk (Recurrence Score >30).
Dr. Donald Burke[/caption]
Donald S. Burke, M.D.
Dean of the University of Pittsburgh Graduate School of Public Health
Director of the University of Pittsburgh Center for Vaccine Research
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Burke: At the University of Pittsburgh we developed a unique method for detecting antibodies in the blood of patients in a proof-of-principle study that opens the door to development of simple diagnostic tests for diseases for which no microbial cause is known, including auto-immune diseases, cancers and other conditions.
We used a technique pioneered by co-author Thomas Kodadek, Ph.D., of the Scripps Research Institute, that synthesizes random molecular shapes called “peptoids” hooked onto microscopic plastic beads. The technique can produce millions of molecular shapes. The peptoids are not organic, but if they match to the corresponding shape on an antibody, that antibody will connect to them, allowing the scientist to pull out that bead and examine that peptoid and its corresponding antibody.
My team chemically generated a huge library of random molecular shapes. Then, using blood from HIV-infected patients and from non-infected people, we screened a million of these random molecular shapes to find the ones that bound only to antibodies present in the blood of HIV-infected patients, but not the healthy controls. No HIV proteins or structures were used to construct or select the peptoids, but the approach, nonetheless, successfully led to selection of the best molecular shapes to use in screening for HIV antibodies.
We then resynthesized that HIV-antibody-targeting peptoid in mass and tested it by screening hundreds of samples from the Multicenter AIDS Cohort Study (MACS), a confidential research study of the natural history of treated and untreated HIV/AIDS in men who have sex with men (supported by the National Institutes of Health). Study co-author Charles Rinaldo, Ph.D., chair of Pitt Public Health’s Department of Infectious Diseases and Microbiology and director of the Pittsburgh arm of the MACS, selected the samples, but blinded the testers to which samples were HIV-positive or -negative. The test distinguished between the samples of HIV-positive blood and HIV-negative blood with a high degree of accuracy.
Dr. Arjun Balar[/caption]
Dr. Arjun Balar MD
Assistant Professor, Department of Medicine
Co-Leader Genitourinary Cancers Program
NYU Langone Medical Center
Laura and Isaac Perlmutter Cancer Center
MedicalResearch.com: What is the background for this study?
Dr. Balar: Standard treatment for advanced urothelial cancer includes cisplatin chemotherapy. But more than half of patients are not expected to tolerate
it well and alternative treatment is inferior to cisplatin. The average survival for these patients is in the range of 9-10 months with carboplatin-based treatment, which is the most commonly used alternative
to cisplatin. Atezolizumab is a PD-L1 blocking antibody that reactivates
the body¹s immune system to fight bladder cancer and has been recently
FDA approved in the management of advanced urothelial cancer in the
second-line setting after failure of platinum-based chemotherapy.
Dr. Robert Ferris[/caption]
Robert L. Ferris, M.D., Ph.D.
Robert L. Ferris, M.D., Ph.D.
UPMC Endowed Professor and Vice-Chair
Associate Director for Translational Research
Co-Leader, Cancer Immunology Program
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Ferris: Investigators at the University of Pittsburgh Cancer Institute<http://upci.upmc.edu/> (UPCI) co-led CheckMate-141<https://clinicaltrials.gov/ct2/show/NCT02105636> a large, randomized international phase III clinical trial that enrolled 361 patients with recurrent or metastatic head and neck squamous cell carcinoma who had not responded to platinum-based chemotherapy, a rapidly progressing form of the disease with an especially poor prognosis. Patients were randomized to receive either nivolumab or a single type of standard chemotherapy until tumor progression was observed.
Nivolumab, which belongs to a class of drugs known as immunotherapeutics, enables the body’s immune system to destroy cancer cells. It currently is approved to treat certain types of cancers, including melanoma and lung cancer. The nivolumab group achieved better outcomes than the standard chemotherapy group by all accounts. After 12 months, 36 percent of the nivolumab group was alive, compared to just 17 percent of the standard chemotherapy group.
Nivolumab treatment also doubled the number of patients whose tumors shrunk, and the number whose disease had not progressed after six months of treatment. Importantly, these benefits were achieved with just one-third the rate of serious adverse events reported in the standard chemotherapy group. In addition, on average, patients receiving nivolumab reported that their quality of life remained stable or improved throughout the study, while those in the chemotherapy group reported a decline. The new trial was considered so successful that it was stopped early to allow patients in the comparison group to receive the new drug.
Dr. Laura Ferris[/caption]
MedicalResearch.com Interview with:
Laura Ferris, M.D., Ph.D.
Associate professor, Department of Dermatology
University of Pittsburgh School of Medicine and
Member of the Melanoma Program
University of Pittsburgh Cancer Institute
MedicalResearch.com: What is the background for this study?
Dr. Ferris: Rates of melanoma, the most dangerous form of skin cancer, are on the rise, and skin cancer screenings are one of the most important steps for early detection and treatment. Typically, patients receive skin checks by setting up an appointment with a dermatologist. UPMC instituted a new screening initiative, which was modeled after a promising German program, the goal being to improve the detection of melanomas by making it easier for patients to get screened during routine office visits with their primary care physicians (PCPs). PCPs completed training on how to recognize melanomas and were asked to offer annual screening during office visits to all patients aged 35 and older. In 2014, during the first year of the program, 15 percent of the 333,788 eligible UPMC patients were screened in this fashion.
Dr. Catherine Diefenbach[/caption]
Dr. Catherine S. M. Diefenbach MD
Assistant Professor of Medicine
NYU Cancer Center
New York, NY 10016
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Diefenbach: It is well known that age is important prognostic factor in non-Hodgkin’s lymphoma (NHL). Multiple studies have illustrated that elderly lymphoma patients have inferior survival outcomes as compared to their younger counterpart. While the tumor biology is often different in these two groups, and may play a role in this discordancy, elderly patients are often frail or have multiple medical comorbidities. These include geriatric syndromes, such as: cognitive impairment, falls, polypharmacy, and potentially inappropriate medication (PIM) use. All of these may contribute to poor outcomes for elderly patients. In addition, elderly patients are often under-treated for their aggressive lymphoma out of concern for toxicity or side effects, even though the data clearly demonstrates that elderly patients can still benefit from curative intent chemotherapy.