Cancer Research
05 Feb New Enzyme Pathway May Inhibit BRAC1 and BRAC2 Tumor Growth
MedicalResearch.com Interview with:
Agnel Sfeir PhD Assistant Professor
Skirball Institute - NYU
New York, NY 10016
Medical Research: What is the background for this study? What are the main findings?
Dr. Sfeir: The main finding of this study, published in the journal Nature, is that inhibiting the action of a particular enzyme dramatically slows the growth of tumor cells tied to BRCA1 and BRCA2 genetic mutations which, in turn, are closely tied to breast and ovarian cancers.
This discovery about the enzyme — called polymerase theta, or PolQ — resulted from efforts to answer a fundamental biological question: How do cells prevent the telomere ends of linear chromosomes, which house our genetic material, from sticking together? Cell DNA repair mechanisms can stitch together telomeres broken as part of cell metabolism. But such fusions, the researchers say, compromise normal cell growth and survival.
In the purest biological sense, our findings (in experiments in mice and human cells) show how this particular enzyme, which we know is active in several tumors, promotes unwanted telomere fusions by inserting whole segments of DNA via a disruptive DNA repair pathway termed alt-NHEJ. It was quite remarkable to find that by blocking PolQ action, cancer cell growth was cut by more than half.
Additional experiments confirmed that PolQ is needed to activate the alt-NHEJ pathway of DNA repair. Unlike the main, error-free pathway — or HDR pathway — the alt-NHEJ pathway does not use a related chromosome’s genetic material as a template to meticulously correct any damaged genetic material. As such, alt-NHEJ is highly likely to leave coding mistakes.
02 Feb Higher Birthweight Linked to Increased Childhood Cancer Risk
MedicalResearch.com Interview with: Kate A O’Neill Department of Paediatrics University of Oxford Children’s Hospital John Radcliffe Hospital Oxford UK MedicalResearch.com: What is the background for this study? Dr. O'Neill: Cancer affects around 1 in 500 children under the age of 15. Although the diagnosis and treatment of these diseases have seen major advances over the past few decades, survivors often experience health complications later in life, and cancer remains the main cause of disease related death in children in the developed world. The identification of risk factors for a number of adult cancers has allowed awareness and screening campaigns aimed at preventing disease. For the majority of childhood cancers, however, we still do not know what causes them, and so similar preventative measures are at present not possible. Incidence rates for many childhood cancers peak within the first few years of life, suggesting that the causative events occur early. For childhood leukaemia, it has even been shown that pre-malignant cells are already present at birth, indicating the disease may originate in utero. Studies exploring potential prenatal risk factors for childhood leukaemia have consistently found that children with the disease have higher birthweights than children who do not, and it is now widely accepted that the faster a foetus grows, the higher the risk of developing leukaemia in childhood. Leukaemia is the most common childhood cancer, accounting for approximately one third of all cases. Other childhood cancers are rarer, and it is consequently harder to perform similar risk association studies. The aim of this study was to compile information on large enough numbers of cases and controls to allow the analysis of risk associations between birthweight and all types of childhood cancer. Furthermore, we compiled data in different countries (USA and UK) to allow the comparison of results from two independent populations. MedicalResearch.com: What are the main findings? Dr. O'Neill: We found that with each 0.5kg (1.1lb) increase in birthweight, the risk of childhood cancer increased by 6%. Compared to babies with average birthweights (3-3.49kg, or 6.6lb -7.7lb), babies with clinically high birthweights (4kg, or 8.8lb, and above) had an increased risk of between 16% and 20%. These increased risks were strongest for certain cancers:- Leukaemias
- Tumours of the central nervous system
- Renal tumours
- Soft tissue sarcoma
- Neuroblastoma
- Lymphoma
- Germ cell tumours
- Malignant melanomas
31 Jan Fear of Cancer Stops Some Patients From Getting Screened
MedicalResearch.com Interview with:
Miss Charlotte Vrinten, MSc, BA, BSc
Research psychologist
Cancer Research UK Health Behaviour Research Centre
Department of Epidemiology and Public Health
University College London
Medical Research: What is the background for this study? What are the main findings?
Response: Many people are afraid of getting cancer, but fear doesn’t have the same effect on everyone. For some people, cancer fear motivates them to get checked up, for others it puts them off finding out whether they have cancer. No-one before has worked out why fear might have such opposite effects. We hypothesized that it might be due to how people experience fear, because some fearful people tend to worry a lot about cancer, while others feel physically uncomfortable thinking about it. In our study, instead of using a combined measure of cancer fear as is often done, we distinguished these different aspects of fear to see whether they had different effects on people’s decisions about cancer screening. We found that the effect of cancer fear depended on the type of fear: worriers were more likely to want to get screened for colon cancer, but those who felt uncomfortable thinking about cancer were 12% less likely to go for the test. Twelve percent may not seem like a lot, but given that tens of thousands of people are eligible for this type of screening, it means a big difference in the number of people actually having the test.
30 Jan Integrated Health Care Reduced Racial Disparities in Colon Cancer Treatment
Posted at 20:12h
in Author Interviews, Colon Cancer, Journal Clinical Oncology, Race/Ethnic Diversity, Stanford, Surgical Research
MedicalResearch.com Interview with:
Kim F. Rhoads, MD, MS, MPH, FACS
Assistant Professor of Surgery
Director, Community Partnership Program
Stanford Cancer Institute Unit Based Medical Director, E3 Surgery and Surgical Subspecialties Stanford University Stanford, Ca 94305
Medical Research: What is the background for this study? What are the main findings?
Dr. Rhoads: Colon cancer is the 3rd most common cancer in US men and women and is the 2nd most common cause of cancer death. For at least 2 decades, minorities with colon cancer have suffered a 15-20% additional risk of death when compared with non-minority patients. Our study set out to understand the influence of the location where treatment was delivered and the quality of care received, on overall survival and racial disparities.
We examined more than 30,000 patients who were diagnosed and treated for colon cancer in California from 2001 through 2006. Using cancer registry data linked to state level inpatient data and hospital information, we compared the rates of National Comprehensive Cancer Network (NCCN) guideline adherence and mortality by location of care and by race. We found that patients treated within an integrated health system (IHS) received NCCN guideline based care at higher rates than those treated outside the system—about 3% higher rates of surgery; and more than 20% higher rates of stage appropriate chemotherapy. The rates of guideline based care were nearly equal between the racial groups treated inside the IHS. Propensity score matched comparisons revealed a lower risk of death for all patients and no racial disparities associated with treatment within the Integrated system. For patients treated outside IHS, the disparity in mortality was explained by accounting for differences in receipt of evidence based care by race.
30 Jan New Mayo Model Better Predicts Breast Cancer Risk After Benign Biopsy
MedicalResearch.com Interview with:
Dr. Amy C. Degnim MD
Professor of Surgery
Mayo Clinic, Rochester.
Medical Research: What is the background for this study? What are the main findings?
Dr. Hartmann: Approximately 1 million women in the US every year have a breast biopsy that shows benign findings. We have found that the specific features of the breast tissue seen under the microscope can help to predict the risk of breast cancer in the future. We developed a mathematical formula to calculate breast cancer risk based on the features seen in the biopsy tissue (named the BBD-BC model). We found that using these microscopic features provides more accurate predictions of risk than the previous standard- the Breast Cancer Risk Assessment Tool (BCRAT).
29 Jan Two Gene Mutations Linked To Deadly Ovarian Cancer
MedicalResearch.com Interview with:
Dr. Terry Magnuson PhD
Vice Dean for Research
Department of Genetics, School of Medicine
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina 27599
Medical Research: What is the background for this study? What are the main findings?
Response: Ovarian clear-cell carcinoma is a lethal form of ovarian cancer with limited therapeutic options. Recent patient-derived tumor sequencing studies support a strong genetic basis for the disease, but the roles of gene mutations in cancer causation are still unclear. We observed rapid induction of ovarian clear-cell carcinoma in mice that were genetically engineered to carry mutations in ARID1A and PIK3CA−the two most frequently mutated genes. Comparisons between human and mouse tumors uncovered a downstream role for the Interleukin-6 (IL-6) cytokine-signaling pathway in tumor progression. Thus, ARID1A and PIK3CA mutations cause ovarian clear-cell carcinoma and promote tumor cell growth by acting upon the IL-6 signaling pathway.
29 Jan Study Attacks Breast Cancer Metastases With Seizure Medication
MedicalResearch.com Interview with:
William J. Brackenbury, Ph.D.
MRC Fellow Department of Biology
University of York, Heslington, York UK
Medical Research: What is the background for this study?
Dr. Brackenbury: Metastasis, the spread of cancer cells from the primary tumour to secondary sites, e.g. the lungs or bones, is the main cause of deaths from cancer. However, there are no effective treatments available to slow or stop this devastating aspect of the disease. We and others have found that sodium channels, normally present in neurons and muscle cells, are up-regulated in metastatic breast cancer cells. Sodium channels appear to regulate the behaviour of these cancer cells, helping them to move and squeeze their way out of the primary tumour as they invade and metastasise on their way to distant sites. This suggests that sodium channels might be useful new therapeutic targets for drugs that could slow metastasis.
Medical Research: What are the main findings?
Dr. Brackenbury: Sodium channels are important drug targets for treating epilepsy. We have found that the antiepileptic drug phenytoin, which is a sodium channel blocker, reduces tumour growth and metastasis in a preclinical model of breast cancer. We found that phenytoin reduces proliferation of cancer cells within the primary tumour. It also reduces local invasion of cancer cells into the surrounding fat and muscle, and reduces the number of cells metastasising to distant sites in the liver, lungs and spleen.
29 Jan Genetic Basis For Acute Lymphoblastic Leukemia Drug Toxicity Identified
Posted at 02:29h
in Author Interviews, General Medicine, Journal Clinical Oncology, Leukemia, Pediatrics
MedicalResearch.com Interview with:
Jun J. Yang Ph.D.
Assistant Member Dept. of Pharm. Sci.
St. Jude Children's Research Hospital
Memphis, TN 38105
Medical Research: What is the background for this study? What are the main findings?
Dr. Yang: Mercaptopurine is highly effective in acute lymphoblastic leukemia (ALL) and essential for the cure of this aggressive cancer. However, it also has a narrow therapeutic index with common toxicities. Identifying genetic risk factors for mercaptopurine toxicity will help us better understand how this drug works and also potentially enable clinicians to individualize therapy based on patients’ genetic make-up (precision medicine).
In addition to confirming the role of TPMT, we have identified another important genetic risk factor (a genetic variation in a gene called NUDT15) for mercaptopurine intolerance. Patients carrying the variant version of NUDT15 are exquisitely sensitive and required up to 90% reduction of the normal dose of this drug. TPMT variants are more common in individuals of African and European ancestry, whereas NUDT15 variants are important in East Asians and Hispanics.
29 Jan Targeted MR/Ultrasound Biopsy May Improve Prostate Cancer Diagnosis
MedicalResearch.com Interview with: Mohummad Minhaj Siddiqui, MD Assi
stant Professor of Surgery - Urology
Director of Urologic Robotic Surgery
University of Maryland School of Medicine and
Peter A. Pinto, M.D
Head, Prostate Cancer Section Director, Fellowship Program
Urologic Oncology Branch National Cancer Institute National Institutes of Health Bethesda, Maryland
Medical Research: What is the background for this study? What are the main findings?
Response: For men suspected of having prostate cancer due to an elevated PSA or abnormal digital rectal exam, the next step in their diagnostic workup has traditionally been a standard 12-core biopsy to evenly sample the entire gland. Unlike most other cancers, prostate cancer is one of the few solid tumors left which is diagnosed by randomly sampling the gland with the hope of biopsying the tumor, if it is present. This paradigm has been largely due to the fact that imaging to date has been limited in its ability to identify prostate cancer. Recent advancements in multiparametric MRI of the prostate however has significantly improved clinician's ability to identify regions in the prostate suspicious for cancer. This has led to the emergence of MR/Ultrasound fusion technology which allows for targeted biopsy of the prostate into regions suspicious for cancer.
Although conceptually, it makes sense that a targeted biopsy has the potential to perform better than the standard random sampling of the prostate in the diagnosis of prostate cancer, studies were needed to understand if this is true, and if so, if the improvement was substantial enough to justify the extra expense and effort needed to obtain a MRI guided biopsy. This study performed at the National Cancer Institute's Clinical Center sought to address this clinical question of interest. From 2007-2014, a total of 1003 men suspected to have prostate cancer underwent an MRI of the prostate. If an area of suspicion was seen in the prostate, these men underwent both the targeted biopsy of the suspicious region in the prostate as well as the standard 12-core needle biopsy during the same session. The results from the targeted biopsy were compared to the results of the standard biopsy.
The key findings in this study was that targeted biopsy improved the rate at which high-risk clinically significant cancer was diagnosed by 30%. Of interest, the study also found that low-risk, clinically insignificant disease (the type of prostate cancer that is unlikely to cause any harm to the patient over the course of his natural life) was decreased in diagnosis by 17%. Decrease of diagnosis of such disease has the potential benefit that it could lead to less over-treatment of cancer that never needed to be treated. In a subset of 170 men that ultimately underwent surgery to remove the prostate to treat their cancer, we were further able to examine how well the prostate biopsy reflected the actual cancer burden in the whole gland. It is well known that standard biopsy can actually underestimate the total cancer grade in the whole prostate in upwards of 30-40% of cases. We found that the targeted biopsy was significantly better at predicting whether the patient had intermediate to high-risk cancer compared to standard biopsy. Through further analysis using a statistical method called decision curve analysis, we further found that for men who wish to undergo surgery for intermediate to high-risk cancer, but wish to go on active surveillance for low-risk cancer, targeted biopsy led to better decision making compared to standard biopsy, or even the two techniques combined.
28 Jan Many Breast Cancer Patient Have Limited Understanding Of Their Own Disease
MedicalResearch.com Interview with:
Rachel A. Freedman MD, MPH
Assistant Professor of Medicine, Harvard Medical School
Department of Medical Oncology
Dana-Farber Cancer Institute, Boston, Massachusetts
Medical Research: What is the background for this study? What are the main findings?
Dr. Freedman: Studies have previously looked at how general cancer knowledge may impact health conditions and rates of screening but none (to my knowledge) have focused on one’s knowledge about his/her own breast cancer. We surveyed 500 women who were diagnosed with early-stage breast cancer within the Northern California Cancer Registry and asked questions about their breast cancer subtype (I.e. Hormone receptor status and HER2 status), tumor grade, and stage. We then matched women’s answers to those collected by the registry to examine the correctness of the answers given. We found low overall rates of having knowledge about one’s disease and this was even more apparent for black and Hispanic patients. When education and health literacy were accounted for, disparities in knowledge remains for black women but were narrowed for Hispanic women in some cases.
26 Jan Interval Breast Cancer More Aggressive Than Mammogram Detected Tumors
MedicalResearch.com Interview with:
Dr Jingmei Li
Department of Medical Epidemiology and Biostatistics
Karolinska Institutet Stockholm, Sweden
Medical Research: What is the background for this study? What are the main findings?
Response: Some cancers, such as interval breast cancers, which are detected within two years of a negative mammogram, are associated with more aggressive tumour characteristics and worse prognosis. As women with interval cancers were twice as likely to have a personal of family history of breast cancer, it is likely that there exist inherited variants that predispose a woman to the more aggressive form of the disease. Our study is one of the first to show empirical evidence that screen-detected and interval cancers are different genetically and are two distinct subtypes.
25 Jan Epigenetic Control Protein Allows Melanoma Cells To Metatasize
MedicalResearch.com Interview with: Prof Lukas Sommer. Ph.D. Cell and Developmental Biology University of Zurich Institute of Anatomy Zurich Switzerland MedicalResearch: What is the background for this study? What are the main findings? Prof. Lukas Sommer: Melanoma, the most aggressive of all skin cancers, is often fatal for patients due to the pronounced formation of metastases. Up to date, a melanoma’s rampant growth was mainly attributed to genetic causes, such as mutations in certain genes. However, we now reveal that so-called epigenetic factors also play a crucial role in the formation of metastases in malignant skin cancer. Epigenetic factors do not influence the gene sequence directly, but rather cause certain genes and chromosomal segments to be packed in different densities – and thus make them accessible for reading. In our study we identified “EZH2” as an epigenetic control protein found very frequently in malignant melanoma cells compared to normal cells. In these cells, “EZH2” controls genes that govern both tumor growth and genes that are important for the formation of metastases. We exploited this central position of EZH2 to combat the cancer by using a pharmacological inhibitor to suppress the activity of EZH2. As a result, we were able to prevent the growth and malignant spread of the cancer in an animal model and in human melanoma cells.25 Jan Novel Compound May Shut Down Pancreatic and Triple Negative Breast Cancer Cells
MedicalResearch.com Interview with:
Dr. Patrick Griffin PhD
Professor and Chairman Department of Molecular Therapeutics
Director of the Translational Research Institute
Scripps Research Institute, Jupiter, Florida
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Griffin: We identified a novel synthetic compound known as SR1848 that sharply inhibits the activity and expression of “liver receptor homolog-1” or LRH-1, a protein that plays an important role in the progression of breast and pancreatic cancers.
Our new study shows that SR1848 removes LRH1 from DNA, shutting down expression of LRH-1 target genes, and halts cell proliferation. It’s a novel compound that appears to be a promising chemical scaffold for fighting tumors that are non-responsive to standard therapies.
22 Jan Colorectal Cancer Incidence Rising In Young Adults
MedicalResearch.com Interview with:
Jason A. Zell, D.O., M.P.H.
Program Director, Hematology/Oncology Fellowship Program
Division of Hematology/Oncology
Department of Medicine UC Irvine Health
Medical Research: What is the background for this study? What are the main findings?
Dr. Zell: Colorectal cancer incidence (CRC) has been declining in the U.S. since 1975, due largely to screening for premalignant polyps. Screening in the U.S. begins at age 50 for average risk individuals, and so the vast majority of Young Adults in the U.S. (defined as age 20-39 in our study) are unscreened. Recently, several studies have reported an increased risk of colorectal cancer among U.S. individuals under age 50. In our analysis of 231,544 CRC cases in California over a 22 year period, we identified 5617 cases among Young Adults (age 20-39). As expected, the overall risk of colorectal cancer in Young Adults is low. However, colorectal cancer is increasing among Young Adults as observed in this population-based study, and certain groups remain at particularly high risk. For example, Hispanic Females age 20-29 were observed to have nearly a 16% increase in colorectal cancer risk when comparing the Biannual Percent Change over the course of the study period. Also concerning was the observation that Young Adults were more likely to be diagnosed with colorectal cancer at an advanced stage than adults in the “screened population” (ie, those age 50 and over).
21 Jan Coffee May Lower Melanoma Risk
MedicalResearch.com Interview with: Erikka Loftfield Doctoral student at the Yale School of Public Health Fellow at the National Cancer Institute Medical Research: What is the background for this study? What are the main findings? Response: Previous studies have reported conflicting results on the association between coffee drinking and melanoma. We sought to clarify this relationship using data from the large NIH-AARP Diet and Health Study. We followed over 400,000 retirees aged 50 to 71 years at study entry for an average of 10 years. Participants were asked to report typical coffee intake. During the course of follow-up nearly 3,000 cases of malignant melanoma occurred. In our study, we observed that individuals who reported the highest total coffee intake (4 cups/day) had about 20% lower risk of malignant melanoma compared with those who did not consume coffee.19 Jan Breast Cancer Patients May Benefit From Detailed Nutrition Monitoring
MedicalResearch.com Interview with:
Cecilia Cesa Schiavon
Department of Nutrition, Federal University of Santa Catarina
Florianópolis, Santa Catarina, Brazil
Medical Research: What is the background for this study? What are the main findings?
Response: The study was based on a nutritional intervention for patients undergoing treatment for breast cancer. The intervention took place right after the surgical procedure and lasted about a year, until the end of chemotherapy. The patients were submitted to a special methodology of intervention, aimed at increasing fruit and vegetable intake and reducing red and processed meat, following the World Cancer Research Fund and the American Institute for Cancer Research in the document entitled Food, Nutrition, Physical Activity and the prevention of Cancer: A Global Perspective”.
The main findings show that women undergoing breast cancer treatment may benefit from immediate, individualized, and detailed nutrition monitoring through appropriate nutrition education.
19 Jan New Cancer Fighting Strategy Attacks Telomere Pathway In Difficult Tumors
MedicalResearch.com Interview with:
Lee Zou, Ph.D.
Professor of Pathology, Harvard Medical School
The Jim & Ann Orr MGH Research Scholar
Associate Scientific Director, MGH Cancer Center
Medical Research: What is the background for this study? What are the main findings?
Dr. Lee Zou: Cancer cells must rely on telomerase or the alternative lengthening of telomere (ALT) pathway to maintain telomeres and bypass replicative senescence. The ALT pathway is active in about 10-15% of human cancers, and it is particularly prevalent in specific cancer types, such as osteosarcoma, glioblastoma, and neuroendocrine pancreatic tumors. ALT is a recombination-mediated process. Whether the reliance of cancer cells on alternative lengthening of telomere can be exploited therapeutically was not known.
In our study, we discovered that the ATR kinase is a key regulator of alternative lengthening of telomere. We found that ATR inhibitors disrupt ALT effectively. Furthermore, we found that ATR inhibitors selectively kill ALT-positive cancer cells in a panel of caner cell lines. These findings have suggested the first rational therapeutic strategy for the treatment of ALT-positive cancer.
16 Jan Link Between Inflammation and Breast Cancer Explored
MedicalResearch.com Interview with:
Dr. Jorge Morales-Montor
Departamento de Inmunología
Instituto de Investigaciones Biomédicas
Universidad Nacional Autónoma de México
México City México
MedicalResearch: What is the background for this study?
Dr. Morales-Montor: Cytokines are highly inducible, secretory proteins that mediate intercellular communication in the immune system. They are grouped in several protein families referred as tumour necrosis factors, interleukins, interferons and colony stimulating factors. In recent years, it has become clear that some of these proteins as well as their receptors are produced in the organisms under physiological and pathological conditions. The exact initiation process of breast cancer is unknown, although several hypotheses have emerged. Inflammation has been proposed as an important player in tumor initiation, promotion, angiogenesis and metastasis, all phenomena in which cytokines are prominent players. The data we have hitherto let us suggest that cytokines play an important role in the regulation of both induction and protection in breast cancer. This knowledge could be fundamental for the proposal of new therapeutic approaches to particularly breast cancer and other cancer related disorders.
16 Jan Risk of Prostate Cancer Reclassification Varies With Time
MedicalResearch.com Interview with: Mufaddal Mamawala, MBBS, MPH, CPH Biostatistician Johns Hopkins School of Medicine Brady Urological Institute Medical Research: What is the background for this study? What are the main findings? Dr. Mamawala: Twenty years after prostate-specific antigen (PSA) was FDA approved for the diagnosis of prostate cancer, its use remains highly controversial. There has been an ‘over- diagnosis’ and ‘over-treatment’ of low-risk prostate cancers that would have never progressed to a more lethal form of the disease during one’s life. Active surveillance (AS) is an alternative to immediate treatment, which allows for monitoring of favorable risk patients with selective delayed intervention among those with disease progression. However ‘misclassification’ is a cause of concern for patients in the initial years of been in AS. The initial biopsy may have missed an area of prostate with an aggressive cancer, due to under-sampling of cores or due to randomness, such that this patient could get misclassified as having a low-risk disease and by the time the follow-up biopsy shows an aggressive cancer the window of curability is lost. However with more sampling of the prostate there is more likelihood to find an aggressive cancer. As such if the patient is compliant with their biopsies, and more prostate is sampled under the microscope, better are the chances of finding a higher risk cancer. Conversely if the patient has more biopsies that show no high-risk cancer then they are less likely to have a high-risk cancer on future biopsies. Thus we wanted to evaluate the risk of reclassification, from a low-risk disease to a high-risk disease (higher Gleason score, or increase in extent of the disease), over a period of time in compliant active surveillance patients. The length of time under Active surveillance without reclassification has not been evaluated as a predictor of future reclassification. Biopsies are invasive procedures, and the fact that patient has to undergo this invasive procedure regularly is a deterrent from been in Active surveillance. This study would help to make informed decisions about the need for doing frequent biopsies in light with other clinical factors especially in older patients who had many non-reclassifying biopsies before. We found that the risk of reclassification was not equally distributed across time. As a result of ‘under sampling’ of prostate at diagnostic biopsy we had highest rates of reclassification in the first two years of been in Active surveillance with more than 50% of total reclassifications happening during those two years. The ‘low-risk’ and the ‘very-low-risk’ groups, determined by the Epstein criteria, had similar rates of reclassification in the first two years. After first two years the ‘low-risk’ group were 2.4 times as likely to have a higher risk of reclassification than the ‘very-low-risk’ group. In both the groups the risk of reclassification declined over time significantly by at least 30% with each biopsy that did not show reclassification.15 Jan Spending on Cancer Rises Sharply Over Ten Year Period
MedicalResearch.com Interview with: Anita Soni, PhD, MBA Survey Analyst/Statistician Project Officer, AHRQ Healthcare Data Analytics and Statistical Products Contract Center for Financing, Access and Cost Trends Agency for Healthcare Research and Quality Rockville, MD 20850 Medical Research: What is the background for this study? What are the main findings? Dr. Soni: The data used for this comes from...
14 Jan Melanoma: BRAF Inhibition May Switch Cancer Cells To Become More Metastatic
MedicalResearch.com Interview with:
Keiran Smalley, PhD.
Scientific Director, The Comprehensive Melanoma Research Center
Associate Professor The Moffitt Cancer Center & Research Institute, Tampa, FL
Medical Research: What is the background for this study? What are the main findings?
Dr. Smalley: Although many patients with BRAF mutant melanoma respond very well to BRAF inhibitors and the BRAF/MEK inhibitor combination, resistance is commonplace and the majority of those treated ultimately fail therapy. Most studies to date have focused upon the genetic changes that are associated with acquired BRAF and BRAF/MEK inhibitor resistance. We decided to take a different approach and to use proteomics to comprehensively map all of the signaling changes associated with resistance. Our study showed that melanoma cells with resistance to BRAF and BRAF/MEK inhibition were highly invasive and aggressive. This aggressive phenotype was driven through a cell surface receptor called EphA2, and this became upregulated in both melanoma cell cultures and in patient tumors following BRAF inhibitor treatment. As this suggested that the resistant cells would be more metastatic, we then performed animal experiments and analyzed tumors from melanoma patients receiving BRAF inhibitor. These studies showed an increase in EphA2 expression in the metastatic tumors that was lacking in the primary tumors. When we looked at cohorts of melanoma patients who received either a BRAF inhibitor or an older chemotherapy drug, we found that more of the BRAF inhibitor treated patients seemed to develop disease at new sites. Together this suggested that BRAF inhibition may switch the cancer cells to being more metastatic.
14 Jan Race and Ethnicity Affect Breast Cancer Diagnosis and Survival
MedicalResearch.com Interview with:
Javaid Iqbal, MD, MSC (Candidate)
Institute of Medical Sciences, and
Women’s College Research Institute/Women’s College Hospital
University of Toronto, Toronto Canada
What is the background for this study? What are the main findings?
Dr. Iqbal: A woman’s racial/ethnic background predicts her participation in breast cancer control program (i.e., awareness and screening). The ultimate objective of breast cancer control program is to detect cancer at an optimal stage, which is stage I, because women with stage I breast cancer survive longer. Given the racial/ethnic diversity of North America, this poses questions such as “what predicts stage I breast cancer in the multiethnic North American population?”, “what predicts its survival?”, and “does a woman’s ethnic background plays a role in predicting an early stage, and survival?”
We studied 373,563 women diagnosed with invasive breast cancer in the United States between 2004 and 2011. We followed these women for 7 years and recorded whether or not they died of breast cancer, or whether they are still alive. We then divided all women into different ethnic groups, in particular white, black, Chinese, Japanese, and Indian/Pakistani (South Asian). For each racial/ethnic group, we estimated proportions of women who were diagnosed with stage I breast cancer, and risk of death at 7 years. Our aim was to determine if the racial/ethnic differences in early stage breast cancer, and its survival were better explained by intrinsic biological differences in tumor characteristics, or by differences in early-detection of breast cancer.
We found that a woman’s racial/ethnic background predicted the diagnosis of stage I breast cancer, as well as her risk of dying at 7 years after breast cancer. A black woman was less likely than a white woman to be diagnosed with stage I breast cancer. A black woman was also more likely than a white woman to die of stage I breast cancer 7 years after her diagnosis. The Japanese and Chinese women were more likely than white women to be diagnosed with stage I breast cancer. The risk of death at 7 years was lowest for Indian or Pakistani (South Asian) women. Furthermore, even for small sized (2.0) breast cancers the risk of death at 7 years was higher for black women (9%), compared to white women (5%). Compared to white women, small sized breast cancers in black women were more aggressive at diagnosis, and had spread to lymph nodes and other organs.
13 Jan Melanoma: Study Support 6mm Criteria in ABCD Rule
MedicalResearch.com Interview with: Razieh Soltani-Arabshahi, MD, MSci Department of Dermatology, University of Utah, Salt Lake City, Utah MedicalResearch.com: What is the background for this study? Dr. Soltani-Arabshahi: The incidence of melanoma is rapidly rising. Dermatologists are the leading specialty group to diagnose melanoma. While ABCD cirteria for diagnosis of melanoma have been used by many dermatologists, there are few studies of it's predictive value. MedicalResearch.com: What are the main findings? Dr. Soltani-Arabshahi: We showed that at an academic dermatology center, nearly 16 clinically suspicious lesions need to be biopsied to find one case of melanoma. Biopsies of lesions larger than 6 mm in diameter on older male patients had the highest yield.13 Jan Twist1 Necessary For Squamous Cell Tumor Formation and Progression
MedicalResearch.com Interview with : Cédric Blanpain, MD, PhD Professor of Stem Cell and Developmental Biology WELBIO, Interdisciplinary Research Institute (IRIBHM) Université Libre de Bruxelles Belgium MedicalResearch.com : What is the background for this study? What are the main findings? Dr. Blanpain: Squamous cell carcinoma (SCC) represents the second most frequent skin cancer with more than half million new patients affected every year in the world. Cancer stem cells (CSCs) are a population of cancer cells that have been described in many different cancers including skin SCCs and that feed tumor growth. These cells could be resistant to therapy thus being responsible for tumor relapse after therapy. However, still very little is known about the mechanisms that regulate Cancer stem cells functions. In a new study published and making the cover of Cell Stem Cell, researchers led by Pr. Cédric Blanpain, MD/PhD, professor and WELBIO investigator at the IRIBHM, Université libre de Bruxelles, Belgium, report the mechanisms regulating the different functions of Twist1 controlling skin tumour initiation, cancer stem cell function and tumor progression. Benjamin Beck and colleagues used state of the art genetic mouse models to dissect, the functional role and molecular mechanisms by which Twist1 controls tumor initiation, cancer stem cell function and tumor progression. In collaboration with Dr Sandrine Rorive and Pr Isabelle Salmon from the department of Pathology at the Erasme Hospital, ULB and the group of Jean-Christophe Marine (VIB, KUL Leuven), they demonstrated that while Twist1 is not expressed in the normal skin, Twist1 deletion prevents skin cancer formation demonstrating the essential role of Twist1 during tumorigenesis. The authors demonstrate that different levels of Twist1 are necessary for tumor initiation and progression. Low level of Twist1 is required for the initiation of benign tumors, while higher level of Twist1 is necessary for tumor progression. They also demonstrate that Twist1 is essential for tumor maintenance and the regulation of cancer stem cell function. The researchers also uncovered that the different functions of Twist1 are regulated by different molecular mechanisms, and identified a p53 independent role of Twist1 in regulating cancer stem cell functions.12 Jan Nanomedicine Platform Uses Fluorescence Imaging To Seek and Destroy Cancer Cells
MedicalResearch.com Interview with:
Oleh Taratula, Ph. D.
Assistant Professor of Pharmaceutics
Department of Pharmaceutical Sciences
College of Pharmacy Oregon State University
Corvallis, OR 97331-3507
Medical Research: What is the background for this study? What are the main findings?
Dr. Taratula: Our research group is focused on the development of novel nanotechnology-based approaches to treat different cancers, including ovarian cancer. For many cancers, surgery is a first choice of treatment. For example, only optimal surgical resection of most abdominal metastases can significantly reduce ovarian cancer recurrence and, therefore, improve patient survival. However, it is challenging to remove most of the cancer tumors and residual cancer cells eventually may lead to cancer relapse. Therefore, our aim is to develop a nanomedicine platform, which could help surgeons achieve maximal tumor resection, using the intraoperative guidance with real-time near infrared (NIR) fluorescence signal. Moreover, we expect that the same nanoplatform could further enhance surgical outcomes by combinatorial phototherapy to be performed intraoperatively after tumor resection to eradicate unresected cancer cells.
Our data published in Nanoscale is the first step towards our main goal. At this point, by utilizing naphthalocyanine, we have developed a single-agent-based nanomedicine platform capable of both NIR fluorescence imaging and combinatorial phototherapy. Naphthalocyanine is a commercially available compound, but its potential clinical application is limited by low water solubility and aggregation. Especially, aggregation diminishes the imaging ability and phototherapeutic efficacy of this compound. To address these shortcomings, we discovered that the loading of naphthalocyanine into the dendrimers significantly enhances water solubility, prevents aggregation and preserves imaging and therapeutic abilities. Our data demonstrated that naphthalocyanine-based nanoplatform can generate a NIR fluorescence signal in the cancer tumors, required for elimination of autofluorescence from healthy tissue and body fluids. Furthermore, our results also indicated that the developed nanoplatform is an efficient therapeutic agent which, upon exposure to NIR light, destroys chemotherapy-resistant ovarian cancer tumors by producing both heat and toxic reactive oxygen species.
Finally, many organic fluorophores, including naphthalocyanine, can undergo photobleaching under exposure to light, which could be misinterpreted as a lack of fluorescence signal during the surgery. We demonstrated that the dendrimer encapsulated naphthalocyanine exhibits extremely high photostability and could overcome the above mentioned issue.
12 Jan Socioeconomic Status Affects Long Term Childhood Leukemia Survival
MedicalResearch.com Interview with:
Professor Eleni Petridou
Preventive Medicine & Epidemiology, Department of Hygiene
Epidemiology and Medical Statistics,
Athens University Medical School Athens Greece
Medical Research: What is the background for this study? What are the main findings?
Prof. Petridou: Impressive gains in survival from childhood leukemia have been achieved during the last decades mainly on account of advancements in treatment of the disease. Yet, these big improvements do not seem to be equally shared by all sick children. Disparities in the survival of children suffering leukemia who live in high versus low-income countries, as well as among different racial groups pointed to socio-economic status (SES) of the family as a factor that might adversely affect the outcome. SES, however, is a multifaceted variable comprising economic, social and professional components, which cannot be easily assessed. Therefore, an array of area of residence- and individual family- based proxy indices have been used in order to investigate the association between SES and overall or event-free survival from childhood leukemia. We have intensively searched for published articles around the globe and also analyzed primary data kindly provided by the US National Cancer Institute Surveillance, Epidemiology and End Results Program (SEER) for the period 1973-2010 as well as the Nationwide Registry for Childhood Hematological Malignancies (NARECHEM) in Greece for the period 1996-2011. This study is the first meta-analysis summing up the findings of 29 individual studies and quantifying the adverse effect in the survival due to SES differentials among 60 000 afflicted children. According to the findings, lower socio-economic status children suffering, at least, the more common Acute Lymphoblastic Leukemia (ALL) type have nearly two fold higher death rates compared to those of high socio-economic status. Of note, the SEER data show that the survival gap was wider in the USA with increased risk of death from ALL in the lower SES children (by 20-82%) and widening during the last 40 years time period.
11 Jan Novel Gene Is Potential Therapeutic Target for Triple Negative Breast Cancer
MedicalResearch.com Interview with: Dr. Pentao Liu PhD and Dr. Walid Khaled PhD Wellcome Trust Sanger Institute Cambridgeshire United Kingdom Medical Research: What is the background for this study? What are the main findings? Dr. Pentao Liu: The significance of this research is that it aims to tackle the worst type of breast cancer. Triple Negative Breast Cancer (TNBC) has the poorest patient survival rate compared to other forms of breast cancer. At present there are no targeted therapies available for TNBC, leaving the non-specific chemotherapy as the only treatment option. In this study we identify a new key gene in Triple Negative Breast Cancer which could potentially be inhibited for the targeted treatment of TNBC. In this study we report the identification of a novel gene for Triple Negative Breast Cancer. By analyzing genomics data from 3,000 patients we find BCL11A to be highly expressed in TNBC. We then demonstrate experimentally that upregulation of BCL11A drives tumour development while its downregulation leads to reduction in tumour size. In the experimental mouse model, inactivation of this gene completely abolishes breast tumour development.11 Jan Risk-Benefits of Tamoxifen for Breast Cancer Prevention
MedicalResearch.com Interview with:
Hazel B. Nichols, PhD
Assistant Professor, Department of Epidemiology
University of North Carolina
Gillings School of Global Public Health
MedicalResearch:What is the background for this study?
Dr. Nichols: Tamoxifen, a drug that is often used to treat breast cancer, has also been approved to prevent breast cancer in women who may be at high risk for developing the disease. Taking tamoxifen for 5 years can lower breast cancer risk by up to 48%. The United States Federal Drug Administration (FDA) approved tamoxifen for breast cancer prevention more than 15 years ago (in 1998) for women ages 35 and older who are at high risk of breast cancer and who are at low risk for serious side effects.
National estimates show that <1% of women who are eligible to use tamoxifen actually use it for breast cancer prevention. While tamoxifen lowers breast cancer risk it does cause hot flashes and may lead to serious side effects such as cataract, stroke, and uterine cancer. Women who start taking may also stop taking it before the recommended 5-years due to side effects.
We used a tool developed by scientists at the National Cancer Institute (NCI) to calculate whether the benefits of tamoxifen outweighed the risks for women in the Sister Study, a study of more than 50,000 U.S. and Puerto Rican women with a family history of breast cancer. The tool uses information on a woman’s age, race, breast cancer risk, menopausal status, and whether she had a hysterectomy (surgical removal of the uterus) to estimate whether there is no, moderate or strong evidence that the benefits of tamoxifen will outweigh the risks.
10 Jan Tumor Marker E2F4 Linked to Breast Cancer Survival
MedicalResearch.com Interview with:
Dr. Chao Cheng PhD
Department of Genetics
Geisel School of Medicine at Dartmouth
Hanover 03755, NH
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Chao Cheng: Cancer survival prognosis—“How long do I have, Dr.?” is a topic of great importance to cancer patients and their families. While clinical and pathological variables, such as cancer type, stage, grade, and patient demographics, have long been used to predict survival outcomes, only recently have molecular signatures become incorporated into survival prediction. A molecular approach holds great promise for improving prediction accuracy and additionally elucidating mechanisms of disease, however it is fraught with difficulty due to assay “noise” and “big data” statistical issues, such as the multiple comparisons problem
In this study, we began by analyzing transcription factor binding profiles across available cell lines. By restricting our analysis to transcription factors, DNA expression regulators known to be involved in tumor genesis, we reasoned that we could avoid many of the “big data” issues and achieve results that would make mechanistic and biological sense. We first employed a statistical method we described previously to calculate which genes were the major downstream targets of our transcription factors. With these targets identified, we then analyzed gene expression data using a bioinformatics method to infer the relative activity of each transcription factor based upon the overall expression levels of their gene targets. From here, we incorporated cancer survival data and examined how each transcription factor’s regulatory activity did, or did not, correlate with survival.
The most prognostic transcription factor was E2F4, a member of the E2F family and a known regulator of the cell cycle. We therefore restricted our analysis to E2F4 and examined how its activity level impacted survival in breast cancer patients.
We found that tumors with high E2F4 regulatory activity as compared to low E2F4 regulatory activity had much worse survival outcomes. These results were stable even after controlling for tumor stage, grade, patient age, and treatment, and were based on data from over 1900 patients across eight independent datasets. These results demonstrate that E2F4 is an independent and enhancing predictor of survival above the currently examined variables.