MedicalResearch.com Interview with: Neel S. Madhukar Graduate student in the lab of Olivier Elemento, PhD, Associate Professor Head, Laboratory of Cancer Systems Biology Department of Physiology and Biophysics Institute for Computational Biomedicine Weill Cornell Medical College Medical Research: What is the background for this study? What are the main findings? Response: It takes on average 2.6 billion dollars and 10-15 years to develop a single new drug. Despite massive investment in drug discovery by pharmaceutical companies, the number of drugs obtaining FDA approval each year has remained constant over the past decade. One of biggest bottlenecks in the process of developing a new drug is to understand precisely how a drug works, that is, what it binds to in cells, how it binds, and what it does when it is bound. This process is collectively called target identification and characterization of mechanisms of action. At present, target identification is a slow and failure-prone process, driven by laborious experimentation. Every time we seek to develop a new drug, such laborious experimentation needs to be redone from scratch. We are not learning from data acquired from our past successes and failures. (more…)
Author Interviews, Dermatology, Genetic Research, Melanoma / 23.04.2015
MedicalResearch.com Interview with: Pedram Gerami, M.D. Associate Professor of Dermatology Director, Melanoma Research Northwestern Skin Cancer Institute Northwestern University MedicalResearch: What is the basis and background for performing this study? Dr. Gerami: Most of the existing literature shows that Sentinel Lymph Node Biopsy (SLNB) will identify 25 to 35 percent of patients who will ultimately die of metastatic melanoma. Hence while SLNB is reported to be the strongest predictor of outcome for melanoma, the vast majority of patients who ultimately die of metastatic melanoma have a negative Sentinel Lymph Node Biopsy result. Hence in this study we aimed to determine whether a GEP assay developed by Castle bioscience could be used independently or in conjunction with SLNB to better detect those patients who are at high risk for developing metastatic disease and dying from melanoma. MedicalResearch: What are the findings of the study? Dr. Gerami: Our study, which examined the use of a Gene Expression Profile (GEP) assay developed by Castle Biosciences and Sentinel Lymph Node Biopsy alone and in combination in a multi-center cohort of 217 patients, demonstrated that the use of the GEP identified more than 80 percent of patients who develop melanoma Combining the two methods showed that patients predicted to be high risk based on the GEP test alone had similar rates of disease progression whether they were SLNB positive or negative. Patients who were SLNB negative and predicted to be low risk using the GEP test had lower rates of disease progression than the SLNB negative group as a whole. (more…)
AACR, Author Interviews, Cancer Research, NIH, Vaccine Studies / 22.04.2015
MedicalResearch.com Interview with: Daniel C. Beachler, PhD Postdoctoral fellow Infections and Immunoepidemiology Branch of the National Cancer Institute (NCI) Medical Research: What is the background for this study? What are the main findings? Dr. Beachler: HPV is a common sexually transmitted infection. Individuals can acquire HPV infections in the epithelium of their cervical, anal and oral sites, and occasionally these infections lead to cancer. There are three prophylactic HPV vaccines on the market that can protect against HPV at these sites among those not been previously exposed to HPV. This study examined the effect of HPV vaccination of 18-25 year old women at all three anatomic sites. The combined multi-site HPV vaccine efficacy has not been reported previously. It was unknown whether the vaccine may protect non-infected sites against HPV infection or re-infection in women exposed to HPV prior to vaccination. We observed that the HPV vaccine provides the strongest protection at all three sites among women unexposed to HPV before vaccination. Additionally, we observed some protection at the non-infected sites in women who were previously infected with HPV. (more…)
AACR, Author Interviews, Biomarkers, Cancer Research / 22.04.2015
MedicalResearch.com Interview with: Timothy Yap, MD, PhD, NIHR BRC The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust London, United Kingdom. Medical Research: What is the background for this study? What are the main findings? Dr. Yap: This is a novel phase I trial assessing for the first time if the PARP inhibitor olaparib can be combined with the AKT inhibitor AZD5363. The study was undertaken at the Royal Marsden and The Institute of Cancer Research in London, England. This targeted combination was based on strong preclinical rationale demonstrating synergy between both drugs in BRCA positive tumors and also antitumor activity in non-BRCA positive tumors. Although olaparib was recently approved by the FDA for treating advanced ovarian cancer associated with defective BRCA genes, antitumor efficacy in different non-BRCA tumors is yet to be established. The key finding for this study was that it was indeed possible to combine both drugs safely, with multiple patients with different cancers responding, including patients with and without BRCA1/2 mutations. We also assessed a new intrapatient dose escalation phase I trial design in this study, and demonstrated that the novel design could be successfully implemented, with completion of the dose escalation phase in 2 schedules of the combination with just 20 patients in 7.5 months. (more…)
AACR, Author Interviews, Genetic Research, Melanoma, NYU, Personalized Medicine, Wistar / 21.04.2015
MedicalResearch.com Interview with: Melissa Wilson, MD, PhD Assisstant Professor Perlmutter Cancer Center NYU Langone Medical Center New York, NY Medical Research: What is the background for this study? What are the main findings? Dr. Wilson: Metastatic cutaneous melanoma is an extremely aggressive form of skin cancer. Traditionally, it has been characterized by clinicopathologic characteristics. More recently, melanoma tumors have also been stratified by common somatic mutations for which targeted therapies have been developed or are under investigation, including BRAF, NRAS and KIT. In addition to somatic mutations, aberrant intracellular signaling pathways and cell cycle disruption contribute to melanoma pathogenesis. Indeed, recent next generation sequencing studies have identified a number of new genes involved in melanomagenesis. A comprehensive evaluation and understanding of concurrent and mutually exclusive mutations in tumors has been lacking. Therefore, we developed a comprehensive custom targeted capture of 108 genes previously implicated in melanoma pathogenesis. We used the targeted panel to perform massively parallel sequencing on 94 well-established human melanoma cell lines, 67 patient-derived xenografts (PDX), and 5 cell lines made from PDX, all untreated. Samples were clustered based on deleterious mutations. Eighty-three percent of samples had deleterious mutations in the MAPK signaling pathway (including BRAF, RAS) and NF1. Ten percent of samples had PI3K pathway mutations which were predominantly associated with BRAF mutations. TP53 was found to be mutated in 24% of the samples and were also associated with mutations in the MAPK pathway. Mutations in chromatin remodeling genes were mutually exclusive with each other, but were associated with BRAF and NRAS mutations. Of particular interest, five of the 10 NF1mutated samples harbored likely deleterious mutations in MAP3K5 or MAP3K9, suggesting the potential involvement of JNK signal transduction pathway in a cohort of samples. (more…)
AACR, Author Interviews, Breast Cancer, UCSD / 21.04.2015
MedicalResearch.com Interview with: Presented by Dr. Maura N. Dickler MD Associate member of the Breast Medicine Service at Memorial Sloan Kettering Cancer Center and Weill Medical College of Cornell University in New York Medical Research: What is the background for this study? This year, breast cancer will claim the lives of nearly 40,000 women in the United States, and up to half of these women will have a disease that is driven by the estrogen receptor.
- Although medicines have been approved for the treatment of hormone receptor-positive breast cancer for decades, more treatment options are needed.
- Resistance to endocrine therapies causes morbidity and mortality for women with metastatic estrogen receptor-positive (ER+) breast cancer as many patients relapse or develop resistance to available hormonal agents via estrogen-dependent and estrogen-independent mechanisms.
- Dual-acting investigational Selective Estrogen Receptor Degrader (SERDs) could potentially lead to a new treatment option for people with hormone receptor-positive breast cancer and may help overcome resistance to current anti-hormonal medicines.
- GDC-0810 is a dual-acting investigational next-generation oral SERD that works in a number of ways to prevent estrogen fueling tumor growth. It is not only designed to target the estrogen receptor (ER) as an antagonist, but also to cause degradation of the ER protein. In preclinical studies, GDC-0810 was shown to induce tumor regressions in both tamoxifen sensitive and tamoxifen resistant tumor models in vivo.
- Clinical data from the dose-escalation portion of a Phase I/IIa study evaluating GDC-0810 appears to have an acceptable safety profile with encouraging anti-tumor activity in postmenopausal women with advanced breast cancer positive for the estrogen receptor (ER), all of whom were previously treated with standard endocrine therapy.
- Promising anti-tumor activity was observed in 38% of patients on study for six months or longer. At all doses tested, there was robust engagement of the estrogen receptor by GDC-0810 as demonstrated by fluoroestradiol (FES) PET scans. Overall, the most common adverse events of any grade related to GDC-0810 were diarrhea, nausea and fatigue.
AACR, Author Interviews, Cancer Research / 20.04.2015
MedicalResearch.com Interview with: Presented by Dr. Jeffrey R. Infante, MD 2015 American Association for Cancer Research Director of the Drug Development Program Sarah Cannon Research Institute in Nashville, Tennessee. Medical Research: What is the background for this study?
- Inhibition of Checkpoint Kinase 1 (Chk1) may be effective at enhancing the effects of chemotherapeutic agents in tumor cells that lack other key cell cycle checkpoint regulators, such as the tumor suppressor protein p53 (p53 mutant tumors).
- In a broad range of pre-clinical models, GDC-0425, an oral, selective Chk1 inhibitor, enhanced the efficacy of the chemotherapy drug gemcitabine. Greater efficacy was also observed in cancer cell lines lacking p53 activity.
- Based on its proposed mechanism of action in enhancing the cytotoxicity of DNA damaging chemotherapy, GDC-0425 was evaluated in combination with a standard dose of gemcitabine.
Author Interviews, Cancer Research / 20.04.2015
MedicalResearch.com Interview with: Pan Pantziarka, PhD Member of the ReDO project and the Anticancer Fund Research from the Repurposing Drugs in Oncology (ReDO) project MedicalResearch: What is the background for this study? Dr. Pantziarka: This study is one of a number initiated by the Repurposing Drugs in Oncology (ReDO) project. ReDO is an international collaboration between the Belgian foundation the Anticancer Fund and the US not-for-profit GlobalCures. ReDO includes researchers based in the UK, Belgium and the US. The project aims to identify the most promising non-cancer drugs which have evidence that they may be effective additions to oncological treatments. Itraconazole, the subject of this study, is a well-characterised and commonly used anti-fungal agent that is available internationally and at relatively low cost. MedicalResearch: What are the main findings? Dr. Pantziarka: We have summarised a broad range of in vitro, in vivo and clinical evidence of anti-cancer activity in itraconazole. In particular there is strong evidence that itraconazole has activity against the Hedgehog signalling pathway, which is active in a variety of different cancer indications. Our study also includes details of a number of positive clinical trials which have reported, and includes details of some still in progress. The level of evidence is particularly striking in basal cell carcinoma, prostate and lung cancer. (more…)
AACR, Author Interviews, Melanoma, Wistar / 20.04.2015
MedicalResearch.com Interview with: Adina Vultur, Ph.D. Staff Scientist Meenhard Herlyn Laboratory Melanoma Research Center The Wistar Institute, Philadelphia Medical Research: What is the background for this study? What are the main findings? Dr. Vulture: Our goal was to identify new drugs with anti-melanoma activity but with minor effects on normal cells. We screened structurally distinct kinase inhibitors first, against multiple cell lines and normal cells, and identified the organometallic compound SM200 as being the most effective and selective molecule, capable of halting melanoma cell growth and invasion. Further characterization of SM200 indicated that PIM kinases are highly inhibited by this compound compared to other targets. We then confirmed the contribution of PIM kinases to melanoma pathobiology by knockdown studies and by using a clinically available PIM-inhibitor. Encouraging results with PIM kinase inhibition in multiple melanoma models including xenografts suggests that this could be a useful strategy against melanoma. (more…)
Author Interviews, Breast Cancer / 20.04.2015
MedicalResearch.com Interview with: Steven Jay Isakoff, MD, PhD Hematology/Oncology Department of Medicine Massachusetts General Hospital Medical Research: What is the background for this study? What are the main findings? Dr. Isakoff: Metastatic triple negative breast cancer remains a challenging clinical problem with no specific therapies targeted validated for this population. From a number of preclinical studies and because of a link between BRCA1 associated breast cancer and triple negative breast cancer, platinum chemotherapy has emerged as a potential chemotherapy with activity in triple negative breast cancer. However, it is not yet clear how to predict which triple negative breast cancer patients are more likely to respond to platinum chemotherapy. We set out to answer several questions.
- First, what is the response rate to platinum chemotherapy in the first or second line for metastatic triple negative breast cancer?
- Second, can we identify biomarkers to predict response to platinum agents? The results of our study showed that among 86 patients treated with platinum chemotherapy (either cisplatin or carboplatin), the response rate was about 25%. We identified 11 BRCA mutation carriers in our population and the response rate among carriers was about 55% compared to about 20% in the non-carriers. In addition, we found that a new assay called the Hologous Recombination Deficiency assay, which may identify tumors with a BRCA-like phenotype, seemed to predict which cancers were more likely to respond, whereas other biomarkers we looked at were not able to do so.
- Another exciting finding was that 6 patients who had major responses have become long term responders with no subsequent progression, some whom for over 5 years so far. Surprisingly, none of the long term responders are BRCA mutation carriers.
AACR, Author Interviews, Cancer Research, Dental Research, Microbiome / 20.04.2015
MedicalResearch.com Interview with: Xiaodan Mai MBBS University at Buffalo, The State University of New York Buffalo, NY MedicalResearch: What is the background for this study? What are the main findings? Response: Periodontal disease is a condition that is highly prevalent amongst the elderly, and is characterized by chronic polymicrobial infection and inflammation of gum tissue. Periodontal disease has been associated with increased cancer risk, and these findings may be partially explained by extra-oral translocation of subgingival bacteria that subsequently modulates host cell environment and function. However, there is limited research on whether the presence of certain subgingival bacteria influences cancer risk. . Oral bacteria have been categorized into color-coded complexes by their timing of colonization and strength of association with periodontal disease. Using data from an ancillary study of the Women’s Health Initiative conducted in Buffalo, New York (a cohort of 1300 postmenopausal women), we therefore investigated the associations between the presence of three early-colonizing periodontal pathogens (Fusobacterium nucleatum, Prevotella intermedia, and Campylobacter rectus, i.e., "orange complex" bacteria moderately associated with PD), the presence of two late-colonizing periodontal pathogens (Porphyromonas gingivalis, Tannerella forsythia, i.e., "red complex" bacteria strongly associated with PD) in dental plaque and cancer risk. We found borderline associations between presence of any early-colonizing pathogens and increased risk of total cancer and lung cancer. Individual pathogens were not associated with total cancer or site-specific cancers when analyzed singly. Presence of any pathogens or presence of any late-colonizing pathogens was not associated with total or site-specific cancer. (more…)
AACR, Author Interviews, Breast Cancer, Nutrition, UCSD / 20.04.2015
MedicalResearch.com Interview with: Catherine Marinac Doctoral Candidate UC San Diego/San Diego State University Joint-Doctoral Program in Public Health La Jolla, CA 92093 MedicalResearch: What is the background for this study? What are the main findings? Response: The dietary advice for cancer prevention usually focuses on limiting consumption of red meat, alcohol, and refined grains, and increasing consumption of plant foods. However, new evidence suggests that other fundamental aspects of diet, such when and how often people eat, can also play a role in cancer risk. For example, research in mice suggests that decreasing the number of hours we eat during the day, and increasing the length of time we fast overnight can improve metabolic parameters and reduce risk of developing a number of chronic diseases including cancer. Similar to the data from animal models, we found that women who fasted for longer periods of time overnight had significantly better control over blood glucose concentrations – and these effects were independent of how much women ate. This finding is relevant to cancer research because people who have poor glucose control are significantly more likely to develop certain types of cancer. It is hypothesized that high concentrations of circulating glucose may fuel cancer growth and progression. (more…)
Author Interviews, Breast Cancer, Cancer Research, Cognitive Issues, JNCI / 19.04.2015
MedicalResearch.com Interview with: Dr. Kerstin Hermelink Senior psychologist Dept. of Gynecology and Obstetrics Ludwig Maximilian University of Munich MedicalResearch: What is the background for this study? What are the main findings? Dr. Hermelink: Many breast cancer patients report problems of cognitive functioning that interfere considerably with their professional and private lives. In the last two decades, a number of studies have confirmed that subgroups of breast cancer patients show at least subtle cognitive impairment. Initially, the condition has entirely been attributed to chemotherapy effects and has therefore colloquially been named “chemobrain”. Meanwhile, however, cognitive impairment has also been found in patients who were managed without chemotherapy and, surprisingly, even in patients who had not yet received any systemic treatment at all. Several hypotheses on the causation of cognitive impairment that occurs already pretreatment have been put forward; for instance, biological effects of the cancer itself might affect cognitive functioning, or there might be shared genetic vulnerability for cancer and cognitive impairment. None of these hypotheses have been empirically confirmed; thus, pretreatment cognitive impairment is as yet unexplained. Our study was designed to investigate the effects of cancer-related post-traumatic stress on cognitive function in breast cancer patients before the start of treatment. Stress has a substantial influence on cognitive functioning, and post-traumatic stress disorder (PTSD) is associated with impairment of cognitive function. While the incidence of full diagnosis of stress disorder is low among breast cancer patients, many of these patients show symptoms of PTSD, with a peak shortly after diagnosis. We did not find an elevated risk of overall cognitive impairment in pretreatment breast cancer patients compared with matched non-cancer controls; however, the cancer patients scored worse than the controls on a small fraction of the cognitive indices that were used. Performance on these indices was indeed robustly associated with PTSD symptoms. Our results therefore indicate that pretreatment cognitive impairment in breast cancer patients may be largely caused by the stress of being diagnosed with cancer. (more…)
Author Interviews, Cancer Research, Mayo Clinic / 15.04.2015
MedicalResearch.com Interview with: Michael B. Wallace, M.D., MPH Mayo Clinic Jacksonville, FL 32224 Medical Research: What is the background for this study? Dr. Wallace: Since its first consideration as an independent entity in 1996,1 intraductal papillary mucinous neoplasms (IPMN) of the pancreas have been diagnosed with increasing frequency. Detection and resection of IPMN offer a unique opportunity to cure and prevent adenocarcinoma of the pancreas, an otherwise highly lethal disease. The main clinical concern related to intraductal papillary mucinous neoplasms is its wide-ranging potential for malignancy from low-risk indolent lesions to those with high incidence of malignant degeneration. It is well-established that this malignant progression varies based on the morphological subtypes. The current methods of predicting malignant potential are limited to clinical, morphological, and cyst fluid cytology and biomarker data. Medical Research: What are the main findings? Dr. Wallace: Of 1126 patients, 84 were diagnosed with invasive carcinoma/high-grade dysplasia and were compared to the rest of the cohort. Multivariate logistic analysis showed no statistically significant association between cancer/high-grade dysplasia and gender, age or alcohol consumption. Smoking history and body mass index was significantly related with cancer/ high-grade dysplasia. Jaundice and steatorrhea were also associated with cancer/ high-grade dysplasia; however, weight loss was not. Univariate analysis showed no association between malignancy and the cyst number/location, although a strong association was shown for cyst size. The presence/size of nodules, and main duct involvement were strongly related with malignancy. (more…)
MedicalResearch.com Interview with: Josée Savard, Ph.D. School of Psychology, Laval University Cancer Research Center Quebec City, Quebec, Canada MedicalResearch: What is the background for this study? What are the main findings? Dr. Savard: This paper reports on a secondary analysis of an 18-month longitudinal study initially conducted in 962 patients about to receive surgery for various types of cancer. The main results of this larger study indicated that insomnia is a significant problem in cancer patients. More precisely, it was found to affect up to 59% of patients at the peri-operative period. In addition, 32% of patients who were good sleepers developed insomnia symptoms at some point during the study (Savard et al., 2009; Savard et al., 2011). The goal of this particular analysis was to determine the role of cancer treatments and their side effects in triggering/aggravating insomnia symptoms during the 18-month follow-up. Study participants completed questionnaires assessing insomnia severity and somatic symptoms at baseline, as well as 2, 6, 10, 14 and 18 months later. This analysis was conducted separately in women treated for breast cancer (n=465) and men treated for prostate cancer (n=263). In breast cancer patients, chemotherapy and radiation therapy, but not hormone therapy, were found to be associated with increased insomnia severity. This deleterious effect appeared to be due to a number of side effects (e.g., nausea, night sweats, urinary symptoms). In prostate cancer patients, androgen-deprivation therapy was associated with aggravation of insomnia, an effect that was mainly due to the occurrence of night sweats. (more…)
Author Interviews, Cancer Research, Cost of Health Care, HPV, Vaccine Studies / 14.04.2015
MedicalResearch.com Interview with: Lillian Siu, MD, FRCPC Princess Margaret Cancer Centre University Health Network Toronto Medical Research: What is the background for this study? What are the main findings? Dr. Siu: Our study is a collaboration between researchers at the Princess Margaret Cancer Centre and the Canadian Center for Applied Research in Cancer Control. The study involves a statistical model being applied to a hypothetical population of 192,940 Canadian boys who were 12 years old in 2012, to determine the cost effectiveness of HPV vaccination for the prevention of oropharyngeal cancer. On the basis of this model, HPV vaccination for boys aged 12 years appears to be a cost-effective strategy for the prevention of oropharyngeal cancer in Canada. There are limitations to our study as it is based on statistical modelling with many assumptions. For instance, we could not easily address the impact of herd immunity which refers to the indirect protective effect offered by HPV vaccination in women. Based on our statistical model, despite its limitations, the vaccine can potentially save $8 to $28 million CAD for a theoretical group of 192,940 Canadian 12-year old boys in 2012 over their lifetime. As stated, this is based on a theoretical model and not a randomized study, the results are relevant especially that HPV-related oropharyngeal cancer is increasing in incidence and HPV is surpassing smoking as a risk factor for this cancer in many developed countries. Currently, the National Advisory Committee on Immunization (NACI) of the Public Health Agency of Canada recommends HPV vaccination of females 9 through 26 years of age to prevent cervical, vulvar, vaginal and anal cancers, and for anogenital warts; and of males 9 through 26 years of age to prevent anal canal cancers and their precursors, and for anogenital warts. However, funding is also provided for HPV vaccination in young females and not in young males. (more…)
Author Interviews, Biomarkers, BMJ, Cancer Research, Gastrointestinal Disease / 14.04.2015
MedicalResearch.com Interview with: Professor Hossam Haick Ph.D Department of Chemical Engineering and Russell Berrie Nanotechnology Institute Haifa, Israel Medical Research: What is the background for this study? What are the main findings? Dr. Haick: Our study is based on the hypothesis that timely detection of premalignant lesions (PMLs) may provide a tool to decrease either cancer mortality or incidence, thought, currently, there is no perfect non-invasive tool to screen for gastric cancer (GC) and the related premalignant lesions. Using 1002 samples collected from 501 volunteers, we show for the first time that premalignant lesions (PMLs) relevant to (gastric) cancer result in detectable differences in Volatile Organic Compound (VOC) signatures that can be detected and classified non-invasively through exhaled breath. We show additionally that these premalignant lesions can be well-discriminated from various stages of gastric cancer as well as other background stomach diseases. (more…)
Author Interviews, Cancer Research, Cost of Health Care, JAMA / 10.04.2015
MedicalResearch.com Interview with: Gabriel Brooks, MD Gastrointestinal Cancer Center Dana-Farber Cancer Institute Medical Research: What is the background for this study? What are the main findings? Dr. Brooks: The background for our study is that hospitalizations in patients with cancer are common, costly, and distressing to patients. Acute hospital care is the single largest expenditure category in cancer care, accounting for substantially greater costs than even chemotherapy. However, patients generally wish to avoid hospitalization, and they certainly want to avoid complications of treatment that can lead to hospitalization. For these reasons, we sought to identify the extent to which hospitalizations are perceived as potentially avoidable by clinicians who are directly involved in patient care. We interviewed three physicians for each of 103 patients with cancer who experienced a hospitalization. For 24 patients (23%) two or more of the three physicians agreed that hospitalization had been potentially avoidable. (more…)
Author Interviews, Genetic Research, Nature, Pancreatic, UT Southwestern / 10.04.2015
MedicalResearch.com Interview with: Dr. Agnieszka Witkiewicz MD Associate Professor of Pathology Harold C. Simmons Comprehensive Cancer Center UT Southwestern MedicalResearch: What is the background for this study? Dr. Witkiewicz: Pancreatic ductal adenocarcinoma (PDA) has a dismal prognosis, with a five year survival rate of approximately 6%. This poor outcome is related to multiple factors, including the relatively late stage of diagnosis, many patients presenting with unresectable disease, and therapy recalcitrance resulting in disease recurrence in spite of operable disease and systemic therapy. Thus far, insights into how to target the treatment of Pancreatic ductal adenocarcinoma have remained unclear in spite of prior sequencing efforts. MedicalResearch: What are the main findings? Dr. Witkiewicz: The underlying critical finding of the study was that Pancreatic ductal adenocarcinoma is genetically diverse and that, in principle, this diversity could be exploited for the treatment of disease. Specifically, many cases harbored deregulation in pathways that are the target for drug development. For example, we identified cases that were driven by BRAF V600E and that were sensitive to the FDA approved drug Vemurafenib. Similarly, multiple cases harbored defects in DNA repair processes that impart sensitivity to select chemotherapeutic agents and PARP inhibitors. Common pathway deregulation was observed in reference to beta-catenin, notch, hedgehog, chromatin remodeling, and cell cycle regulatory pathways that are all targets for therapeutic intervention. (more…)
Author Interviews, Genetic Research, JAMA, Melanoma / 10.04.2015
MedicalResearch.com Interview with: Nancy E. Thomas, MD, PhD Department of Dermatology University of North Carolina MedicalResearch: What is the background for this study? Dr. Thomas: BRAF and NRAS mutations found in melanomas are important for tumor initiation and maintenance. There are drugs that target BRAF mutations or the pathway that are approved for BRAF-mutant metastatic melanoma and help improve survival. However, it remains unknown whether these mutations in primary melanoma are markers for melanomas with a worse prognosis. MedicalResearch: What are the main findings? Dr. Thomas:
- In a large international population-based study, we found that of primary melanomas, 30% harbor BRAF mutations, 13% have NRAS mutations and the other 57% do not have these mutations (wildtype).
- In higher primary tumor stage melanomas, BRAF or NRAS mutations were associated with an approximately 3-fold increased rate of death from melanoma compared to wildtype melanoma adjusted for other prognostic factors.
- Primary melanomas with NRAS mutations were less likely to have tumor infiltrating lymphocytes (TILs) in the tumor microenvironment. (more…)
Author Interviews, Cancer Research, Cost of Health Care / 08.04.2015
MedicalResearch.com Interview with: Stacie B. Dusetzina PhD Assistant professor in the Eshelman School of Pharmacy and the Gillings School of Global Public Health University of North Carolina at Chapel Hill Member of the Lineberger Comprehensive Cancer Center Medical Research: What is the background for this study? What are the main findings? Dr. Dusetzina: Charges for health services — the amounts providers request before payments are negotiated — have not been widely known for services delivered in physicians’ offices. Charges can be considered the maximum amount that would be paid by a person without insurance who does not or is unable to negotiate for a lower price. In this study we used recently released data from the Medicare Provider Utilization and Payment Public Use File and other sources to measure what physicians charged for chemotherapy drugs delivered intravenously in 2012 and the amounts reimbursed by Medicare and private health plans for the same services. We found that uninsured cancer patients may be asked to pay from 2 to 43 times what Medicare pays for chemotherapy drugs. Medicare and insurers don’t pay the sticker price of health care. They pay a discounted rate. However, uninsured patients don’t have the bargaining power, or they may not try to negotiate for a better price. On average, Medicare paid approximately 40 percent of the charged amounts for chemotherapy drugs. Private insurers paid nearly 57 percent of the charged amounts on average. We also looked at what cancer patients were asked to pay for an office visit. Uninsured patients may be asked to pay from $129 to $391, depending on the complexity of the visit. Medicare paid between $65 and $188 and private insurance paid between $78 and $246 for the same visits. (more…)
MedicalResearch.com Interview with: Dr. Riccardo Capocaccia Evaluative Epidemiology Unit Department of Preventive and Predictive Medicine Fondazione Istituto Nazionale Tumori Milan, Italy Medical Research: What is the background for this study? What are the main findings? Dr. Capocaccia: Life expectancy of cancer patients is usually provided at diagnosis, as a measure of cancer burden. However, no systematic data are available on life expectancy at different times after diagnosis, as a measure of the residual impact of the disease in survivors. At diagnosis, young patients face a higher loss in life expectancy, with respect to cancer-free people of the same age, than older ones. Thereafter, life expectancy gradually approaches, but hardly reaches, that of all patients of the general population. (more…)
Author Interviews, Breast Cancer, Genetic Research, Journal Clinical Oncology, University of Michigan / 06.04.2015
MedicalResearch.com Interview with: Dr. Reshma Jagsi MD, DPhil Associate Professor and Deputy Chair for Faculty and Financial Operations in the Department of Radiation Oncology at the University of Michigan Health System Research Investigator at the Center for Bioethics and Social Sciences in Medicine University of Michigan Medical Research: What is the background for this study? What are the main findings? Dr. Jagsi: We surveyed women diagnosed with breast cancer and found that many women were concerned about the genetic risk of developing other cancers themselves or of a loved one developing cancer. Overall, 35 percent of the women we studied expressed a strong desire for genetic testing, but 43 percent of those did not have a relevant discussion with a health care professional. In addition, minority patients with a strong desire for testing were less likely to discuss it with a professional, even though studies show that minority patients are not at lower risk for these mutations. (more…)
Author Interviews, Biomarkers, Lancet, Lymphoma, NIH / 06.04.2015
MedicalResearch.com Interview with: Dr. Mark Roschewski, MD and Dr Wyndham H Wilson MD-PhD Lymphoma Therapeutics Section Lymphoid Malignancies Branch, Center for Cancer Research National Cancer Institute, National Institutes of Health Bethesda, MD 20892 Medical Research: What is the background for this study? What are the main findings? Response: Monitoring patients with diffuse large B-cell lymphoma (DLBCL) has relied on computed tomography (CT) scans which are imprecise, expensive and include radiation. We investigated the ability of a blood-based assay to monitor patients with DLBCL during and after their initial therapy. The assay we studied amplifies and quantifies small amounts of circulating tumor DNA from the patient’s blood. We showed that this assay effectively predicts which patients will relapse and identifies recurrence 3.5 months before CT scans. (more…)
Breast Cancer, Health Care Systems / 06.04.2015
MedicalResearch.com Interview with: Dr. Karla Unger-Saldaña Unit of Epidemiology Instituto Nacional de Cancerología Mexico City, Mexico. Medical Research: What is the background for this study? Dr. Unger-Saldaña: Even though Breast Cancer is most common in the developed world, most cancer deaths actually occur in developing regions. This is mainly because patients are diagnosed in advanced stages, with poor chances of survival. Most studies have shown that long times between symptom discovery and treatment start (total delay) are associated with advanced clinical stage. Like total delay, patient delay -a prolonged time between symptom discovery and the first medical consultation- has also shown to be associated with advanced clinical stage. But the impact of health system delay -the time between the first clinical consultation and the start of cancer treatment- is less clear. Studies have shown contradictory findings. For example, studies in developed countries have found the reverse association: advanced stages associated with short times between first medical consultation and treatment start. This has been attributed to the ability of doctors to quickly identify patients with advanced cancer and somehow accelerate their care. Medical Research: What are the main findings? Dr. Unger-Saldaña: In this study, done among 886 patients, we found that the majority started cancer treatment in advanced stages, with only 15% being diagnosed in stages 0 and I. Also, we found long delays for breast cancer diagnosis and treatment in most cases. The median time between symptom discovery and cancer treatment start was 7 months. The longest subinterval was that between the first medical consultation and diagnosis confirmation, which had a median of 4 months. The most relevant result was that not only was patient delay associated with advanced stage, but also health system delay. For every additional month of health system delay, the probability of starting treatment in advanced stage was increased by 1%. (more…)
Author Interviews, Cancer Research, UCSF / 03.04.2015
MedicalResearch.com Interview with: Trever G. Bivona MD PhD Assistant Professor, Hematology and Oncology UCSF Medical Research: What is the background for this study? What are the main findings? Dr. Bivona: Resistance to targeted cancer therapy remains a problem in the treatment of cancer patients. These targeted drugs are often effective at shrinking the tumor, but do so incompletely. This incomplete response results in residual disease that is drug resistant and eventually grows to cause relapse that is lethal in patients. We investigated the mechanisms underlying this residual disease state in lung cancers treated with the EGFR targeted therapy Tarceva. We discovered that the tumor cells survival initial EGFR targeted therapy treatment by activating a signaling pathway called NF-kappa B. This NF-kappa B pathway then promotes tumor cell survival, residual disease, and eventual relapse in the lung cancer models we studied. (more…)
Author Interviews, Dermatology, Melanoma / 03.04.2015
MedicalResearch.com Interview with: Suzanne Dobbinson PhD Senior Research Fellow Centre for Behavioural Research in Cancer Cancer Council Victoria Melbourne Australia MedicalResearch: What is the background for this study? What are the main findings? Dr. Dobbinson: Australia has one of the highest skin cancer rates in the world due to the country’s high levels of ultraviolet (UV) radiation and a population with susceptible skin types. Two in three Australians will be diagnosed with skin cancer by the age of 70, with more than 40,000 new cases annually in the state of Victoria alone. Since the 1980s there have been broad public education programs to raise awareness of skin cancer. Television campaigns have been central to these multi-component prevention programs, including SunSmart, which is the longest-running program in Victoria. This study examined SunSmart television advertisements broadcast over summers between 1987 to 2011 to determine what effect – if any – these advertisements had on people’s sun protection attitudes and behaviours. Cross-sectional weekly telephone surveys of Melbourne residents were conducted over summers during the study period. Population exposure to campaign TV advertisements was also measured as cumulated weekly target audience rating points (TARPs) for 4 weeks prior to interview. Using multiple logistic and linear regression models, we examined whether there was a relationship between the TARPs and responses of the surveys. We found that increasing TARPs were related to an increased preference for no tan, increased sunscreen use and overall reduced mean percentage of skin exposed to the sun. Also of note was that this behavioural impact was consistent across all age groups. (more…)
Author Interviews, Cancer Research, Nature, NYU / 03.04.2015
MedicalResearch.com Interview with: Alka Mansukhani Ph.D. Associate Professor Department of Microbiology Member of the Laura and Isaac Perlmutter Cancer Center NYU Langone Medical Center Medical Research: What is the background for this study? What are the main findings? Dr. Mansukhani: Osteosarcoma is a highly aggressive pediatric bone cancer that is almost always advanced at diagnosis. Treatment outcomes have not improved in three decades and 40% of patients eventually succumb to the disease. A few years ago we identified that normal bone stem cells relied on the function of a gene called Sox2 to remain immature an self-renew. We went on to find that osteosarcoma cancer stem cells, that arise from immature bone cells, express high levels of Sox2. Like their normal counterparts, these cancer cells also need Sox2. Sox2 maintains the stemness properties of the cancer cells as well as their ability to form tumors in mice. Depleting Sox2 resulted in cells that had reduced tumor-forming potential and instead, were able to become mature bone cells. http://www.stbaldricks.org/blog/post/new-discovery-may-hold-the-key-to-destroying-osteosarcoma/ In this new study we have identified the mechanism by which Sox2 maintains the properties of osteosarcoma cancer stem cells. Sox2 inactivates the growth restraining function of the well-known tumor suppressive hippo pathway. Hippo signaling restrains the activity of a potent oncogene, YAP. In the osteosarcoma stem cells, Sox2 directly represses two genes (Nf2 and WWC1) in the hippo pathway and thereby unleashes the growth promoting activity of YAP. Like Sox2, YAP is required to maintain the tumorigenic properties of osteosarcoma cells. Consistently, we found high YAP and low NF2 and WWC1 expression in human osteosarcoma tissues. Our study makes a direct connection between Sox2 and repression of hippo signaling to enable YAP activity in osteosarcomas. This mechanism also operates in glioblastoma, an aggressive brain tumor. (more…)