Posts Tagged ‘several’

Promising new cancer therapy uses molecular ‘Trash Man’ to exploit a common cancer defense

Cancer therapies cause unwanted proteins to accumulate in cancer cells, which can trigger a form of cell suicide known as apoptosis. To survive, the cells break down the excess proteins through autophagy, from a Greek term meaning “self eating.” In a study recently published in the journal Molecular and Cellular Biology, scientists induced autophagy using the anti-tumor drug obatoclax while simultaneously blocking the production of p62 using a drug known as a cyclin-dependant kinase (CDK) inhibitor. Several experiments involving animal models and cultured multiple myeloma cells demonstrated that blocking p62 disrupted autophagy and killed far more cancer cells than administering the anti-cancer agents alone.

“Therapies that are designed to block the early stages of autophagy do not offer the possibility of exploiting its potentially lethal effects,” says Steven Grant, M.D., Shirley Carter Olsson and Sture Gordon Olsson Chair in Cancer Research, associate director for translational research and program co-leader of Developmental Therapeutics at VCU Massey Cancer Center. “Our strategy turns autophagy from a protective process into a toxic one, and these results suggest it could increase the effectiveness of a variety of cancer therapies that induce autophagy.”

Critical to the success of this therapy is Bik, a protein that plays a significant role in governing cell death and survival. During cancer treatments, Bik accumulates in cancer cells until it triggers apoptosis. Normally, the cancer cells would induce autophagy and p62 would rid the cells of Bik by loading the proteins into degradation chambers known as auotophagosomes for disposal. However, blocking p62 production results in an inefficient form of autophagy and the accumulation of Bik eventually causes the cancer cells to undergo apoptosis.

This research builds upon more than a decade of work by members of Grant’s laboratory investigating novel treatment strategies and combination therapies that selectively kill multiple myeloma and other blood cancer cells. The technology in his study has been made available for licensing through the VCU Office of Research.

“We are now working to identify additional CDK inhibitors that can be used to disrupt autophagy,” says Grant. “The ultimate goal will be to translate these findings into a clinical trial to test the therapy in patients with various blood cancers.”

source : http://www.sciencedaily.com/releases/2014/08/140827112135.htm

Scientists map risk of premature menopause after cancer treatment

The findings, set out in the Journal of the National Cancer Institute, are based on the experience of more than 2,000 young women in England and Wales treated for the cancer over a period of more than 40 years.

Previous research has suggested that women with Hodgkin lymphoma who receive certain types of chemotherapy or radiotherapy are at increased risk of going through the menopause early — but there was insufficient information to provide patients with detailed advice.

But the new study, led by scientists at The Institute of Cancer Research, London, provides precise estimates of risk for women depending on which treatment types and doses they received and at what age — allowing doctors to give them detailed advice about their risks of future infertility.

The research was largely funded by Breakthrough Breast Cancer and involved researchers from across the UK at more than 50 universities and hospitals.

The research team followed-up 2,127 women who had been treated for Hodgkin lymphoma in England and Wales between 1960 and 2004, and who had been aged under 36 at the time. All had received treatment with chest radiotherapy, sometimes alongside other treatments.

Some 605 of the women in the study underwent non-surgical menopause before the age of 40. This was a large enough number for the researchers to estimate accurate risks of menopause at different ages, depending on the mixture and doses of treatments they received and the age they received them.

The researchers produced a risk table which could help improve the advice that clinicians are able to give to women who have undergone treatment for the disease. Several of the treatments caused a sharp increase in premature menopause risk.

For example, a woman who had received six or more cycles of a standard chemotherapy regimen in her late 20s, but without receiving radiotherapy to the pelvic area, had a chance of around 18 per cent of undergoing menopause by the age of 30, or 58 per cent by age 40.

Overall, risk of premature menopause was more than 20-fold raised after ovarian radiotherapy, and also after some specific chemotherapy regimens. Risk of menopause by age 40 was 81 per cent after receiving ovarian radiotherapy at an overall dose of 5 or more Grays, and up to 75 per cent after chemotherapy, depending on the type, although only one per cent after receiving a chemotherapy regimen called ABVD.

Study leader Professor Anthony Swerdlow, Professor of Epidemiology at The Institute of Cancer Research, London, said:

“Hodgkin lymphoma often affects younger women, and although fortunately most survive the disease, treatments including certain types of chemotherapy and pelvic radiotherapy can lead to premature menopause.

“We hope our study will help women to understand better, in consultation with their doctors, their risks of future infertility following treatment for this malignancy. By looking in a much larger group of women than previous studies of this type, we were able to produce age and treatment specific risk estimates that we hope will be of practical use to individual women. I’m extremely grateful to the patients and doctors who made it possible for us to produce this information.”

source : http://www.sciencedaily.com/releases/2014/08/140822094148.htm

Online screening for rare lung cancer mutation opens door to new kind of clinical trial

The University of Colorado Cancer Center is now taking a novel approach to this problem, reaching out via the internet to expand the pool of patients potentially eligible for just such a biomarker-preselected clinical trial. After completing the interactive online screening questions, eligible patients with advanced lung cancer will be consented via the phone to permit a pre-existing biopsy sample of their lung cancer tissue to be shipped to the CU Cancer Center for trial-specific molecular testing. The testing is designed to identify patients who may have lung cancers driven by alterations in the gene FGFR1. Patients whose tumors turn out to be FGFR1-positive and meet the other trial screening criteria will then be offered treatment for their cancer within a clinical trial at CU Cancer Center using the experimental FGFR1 inhibitor drug ponatinib. Ponatinib is already licensed for treating certain blood cancers, but work by CU scientists in laboratory models suggest it may also be a potent agent in some specific molecular subtypes of lung cancer driven by, among other things, changes in the FGFR1 gene.

“FGFR1 has already been explored by the pharmaceutical industry, with rather limited success, but those approaches used a very different way of looking to see if FGFR1 was driving the lung cancer,” says Ross Camidge, MD, PhD, director of the thoracic oncology clinical program at the CU Cancer Center and the trial’s principal investigator. “Based on some really innovative work coming out of our own Specialized Program of Excellence in Lung Cancer, the tests we are employing in this trial seem to define a completely separate subtype of lung cancer — one that has really not been explored before. Now the challenge is in finding enough people whose cancers are positive for our biomarkers to prove whether the markers will predict for clinical benefit from ponatinib.”

Having built the infrastructure to allow nationwide molecular prescreening for the trial, Camidge’s team plans to also use internet awareness to speed accrual into their trial.

“We know that the vast majority of the U.S. population now routinely uses the internet to find out about medical conditions, so we thought we’d get Dr. Google to help us out,” says Camidge. “Several very high profile internet resources for lung cancer patients, including the Bonnie J. Addario Lung Cancer Foundation (BJALCF) and the Global Resource for Advancing Cancer Education (GRACE) have helped us craft this trial and we are very grateful for their commitment to increase awareness about the opportunity it presents for lung cancer patients who might benefit from the molecular prescreening.”

Indeed, Dr Jack West, the CEO of GRACE, co-wrote a position paper with Camidge in the Journal of Thoracic Oncology in 2012 titled “Have Mutation, Will Travel” to highlight the pressing need to transform the way clinical trials are conducted in the new era of molecular diversity.

“While Big Pharma sometimes spends millions of dollars to open biomarker-selected trials at hundreds of different locations to find enough patients, the kind of innovative approaches that are homegrown in university settings will never have the resource to do that,” said Dr West. “Regardless of whether the FGFR1-ponatinib pairing works or not, what the Colorado team is trying to do could really change the future of clinical cancer research for the better. Patients are increasingly becoming empowered about their own cancer care. Anything we at GRACE can do to get the word out about the Colorado approach will be a very good thing.”

Bonnie Addario, chair and founder of the BJALCF and a ten-year lung cancer survivor herself, is similarly enthusiastic. “If we are going to change the survival rates for lung cancer, we have to stop treating everyone the same. We have to do things differently, and if Dr. Camidge’s approach can bring a little bit of Colorado’s expertise into easy reach of anyone with a computer, then this is a new way of accelerating the process and much more convenient for the patient. We will do all we can to assist in getting patients involved in this exciting new approach,” Addario says.

Over the next 3-5 years the Colorado team plans to screen up to 700 lung cancer patients and optimize the biomarker signatures for predicting benefit from ponatinib over time, tweaking the criteria as they go along based on the emerging results in each group of treated patients.

“Clinical research is very expensive and sources of support for this kind of clinical research, as for everything else, are rather limited,” says Camidge. However, Camidge’s novel approach has already allowed him to secure several hundreds of thousands of dollars in support from sponsors including the manufacturer of ponatinib, Ariad, from the CU Cancer Center and from the CU Lung Cancer Specialized Program of Excellence in Lung Cancer.

“However, if this trial takes off, that’s probably only about half of what we’ll need. That’s why we’ve taken to the internet to crowd-source trial accrual through the Consano philanthropy website. It’s amazing — the internet is giving us new opportunities at every turn. I am very optimistic; although we are having to do this on a very limited budget, I know from experience that we can produce major breakthroughs even from a small study if the approach is right,” Camidge says.

Please visit the trial enrollment website, the Consano crowd sourcing website, and the study description at ClinicalTrials.gov to learn more about the study. As the goal of this study is to find as many advanced stage lung cancer patients who might benefit from this trial as possible, Dr. Camidge and his team would be very grateful if you would consider sharing this information via your own social media outlets.

source : http://www.sciencedaily.com/releases/2014/08/140822124458.htm