Posts Tagged ‘materials’

Sabotage as therapy: Aiming lupus antibodies at vulnerable cancer cells

The findings were published recently in Nature‘s journal Scientific Reports.

The study, led by James E. Hansen, M.D., assistant professor of therapeutic radiology at Yale School of Medicine, found that cancer cells with deficient DNA repair mechanisms (or the inability to repair their own genetic damage) were significantly more vulnerable to attack by lupus antibodies.

“Patients with lupus make a wide range of autoantibodies that attack their own cells and contribute to the signs and symptoms associated with lupus. Some of these antibodies actually penetrate into cell nuclei and damage DNA, and we suspected that we may be able to harness the power of these antibodies for use in targeted cancer therapy,” Hansen said.

The genetic code that determines how a cell develops is written in DNA. Damage to this code can cause a cell to malfunction, die, or transform into a cancer cell. Normal cells are equipped to repair damaged DNA and preserve the genetic code, but many cancer cells have defective DNA repair machinery and accumulate genetic mutations.

This difference between normal cells and certain cancer cells creates an opportunity to develop therapies that damage DNA and only kill cancer cells that cannot repair the damage. However, DNA is sequestered inside cell nuclei, where delivery of therapies can be challenging. Yale Cancer Center researchers are finding that naturally occurring lupus antibodies just may be a solution to this problem.

“Lupus antibody-based cancer therapy is an emerging new concept, and I believe we are just seeing the tip of the iceberg in terms of the potential of this approach,” said Hansen.

The researchers previously found that a lupus antibody called 3E10 inhibits DNA repair and sensitizes cancer cells to DNA damage, and they have now found that the DNA-damaging lupus antibody 5C6 is toxic to DNA repair-deficient cancer cells.

“Now that we know that more than one lupus antibody has a selective effect on cancer cells, I am confident that additional lupus autoantibodies with even greater therapeutic potential await discovery,” Hansen said.

source : http://www.sciencedaily.com/releases/2014/09/140902151302.htm

Better classification to improve treatments for breast cancer

Cancer arises due to genetic changes which cause normal cells to develop into tumors. As we learn more about breast cancer, we are seeing that it is not one single disease — the mutations in the genes that cause different cancers are not alike, and this is why tumors respond differently to treatment and grow at different rates. Currently, there are two key markers that clinicians use to predict response to treatments.

Spotting the trends in tumor genetics and creating a system to diagnose tumor types is a primary objective of cancer scientists. To this end, researchers at Cancer Research UK and the University of Cambridge have been developing the IntClust system, which uses genomic technology to create a classification system with enough detail to more accurately pinpoint which type of breast cancer a patient has, and therefore what treatment would be most appropriate.

To test the system, the scientists looked at the 997 tumor samples they had used to develop the system, and 7,544 samples from public databases, along with the genomic and clinical data including data from The Cancer Genome Atlas. They classified these using their IntClust system, and the two main systems in use today — PAM50, which groups cancers into five types, and SCMGENE, which classifies cancer into four.

They found that IntClust was at least as good at predicting patients’ prognosis and response to treatment as the existing system. But the system identified a previously unnoticed subgroup of tumors in just 3.1% of women with very poor survival rates, which appeared to be resistant to treatment. Identifying the genomic signatures for this group could flag up these high risk cancers early, and having the genomic data for these could aid in the investigation of new avenues for treatments for this type of cancer.

At present, using this system to classify tumors would be costly for most clinicians, and interpreting the results requires training that many clinical settings don’t have access to. But the detail and accuracy of this system could be of great use to breast cancer researchers, who will be able to investigate the reasons that certain groups of cancer respond better to certain treatments, in order to find clinical markers, or to identify new targets for breast cancer treatments.

Raza Ali, lead author from Cancer Research UK Cambridge Institute, says: “We have developed an expression-based method for classification of breast tumours into the IntClust subtypes. Our findings highlight the potential of this approach in the era of targeted therapies, and lay the foundation for the generation of a clinical test to assign tumors to IntClust subtypes.”

source : http://www.sciencedaily.com/releases/2014/08/140827203633.htm

Three-quarters of depressed cancer patients do not receive treatment for depression; new approach could transform care

An analysis of data from more than 21,000 patients attending cancer clinics in Scotland, UK, published in The Lancet Psychiatry, found that major depression is substantially more common in cancer patients than in the general population. Major depression was most common in patients with lung cancer (13%) and lowest in those with genitourinary cancer (6%). Moreover, nearly three quarters (73%) of depressed cancer patients were not receiving treatment.

To address the problem of inadequate treatment the SMaRT Oncology-2 randomised trial, published in The Lancet, evaluated the effectiveness of a new treatment program called ‘Depression Care for People with Cancer’ (DCPC). DCPC is delivered by a team of specially trained cancer nurses and psychiatrists, working in collaboration with the patient’s cancer team and general practitioner, and is given as part of cancer care. It is a systematic treatment program that includes both antidepressants and psychological therapy.

The trial, involving 500 adults with major depression and a cancer with a good prognosis (predicted survival more than 12 months) compared DCPC with usual care [1]. DCPC was strikingly more effective at reducing depression. At 6 months, 62% of the patients who received DCPC responded to treatment (at least a 50% reduction in the severity of their depression) compared with only 17% of those who received usual care. This benefit was sustained at 12 months. DCPC also improved anxiety, pain, fatigue, functioning, and overall quality of life. Moreover, the cost of providing DCPC was modest (£613 per patient) making it a cost-effective way to improve cancer patients’ quality of life.

According to lead author Professor Michael Sharpe from the University of Oxford in the UK, “The huge benefit that DCPC delivers for patients with cancer and depression shows what we can achieve for patients if we take as much care with the treatment of their depression as we do with the treatment of their cancer.”

To see if patients with a poor prognosis cancer could also benefit from this approach, the SMaRT Oncology-3 randomised trial, published in The Lancet Oncology, tested a version of DCPC adapted for patients with a typically poor prognosis cancer (lung cancer). The trial, involving 142 patients with lung cancer and major depression, found that those who received the lung cancer version of DCPC had a significantly greater improvement in depression than those who received usual care during 32 weeks of follow-up. The lung cancer-specific version of DCPC also improved anxiety, functioning, and quality of life.

According to study leader Dr Jane Walker from the University of Oxford and Sobell House Hospice in Oxford in the UK, “Patients with lung cancer often have a poor prognosis. If they also have major depression that can blight the time they have left to live. This trial shows that we can effectively treat depression in patients with poor prognosis cancers like lung cancer and really improve patients’ lives.”

source : http://www.sciencedaily.com/releases/2014/08/140827203635.htm