Biomarker Drug for MesotheliomaTreatment

Mesothelin Combined with a MiRNA May Be Effective Diagnostic Biomarker for Mesothelioma

German researchers have shown that a combination of protein and nucleic acid biomarkers improves the diagnostic performance of a blood-based screening test for mesothelioma compared to the use of an individual biomarker from a single molecular class.

Malignant mesothelioma, an aggressive asbestos-caused cancer with a long latency period of 40 or more years, has a low median survival rate of 9-13 months from diagnosis due to the fact that symptoms typically only occur during late stages of the disease. Diagnosis at early stages has the potential to improve therapy and survival, but the development of a reliable blood test has been hindered by the low diagnostic performance of most prominent biomarker to date for mesothelioma—mesothelin.

The biomarker mesothelin, according to the authors of a new study published online by PLUS ONE, is characterized by high specificity (89%) but low sensitivity (58%). That is, in patients with mesothelioma, blood tests that use mesothelin as a biomarker generate false positives 11% of the time and false negatives 42% of the time. The AUC (a measure of diagnostic accuracy) of mesothelin is 0.85.

By combining the protein biomarker mesothelin with the microRNA (miRNA) biomarker miR-103a-3p, the researchers improved the overall diagnostic performance of a blood-based biomarker for mesothelioma to an AUC of 0.93.

“In conclusion,” writer the authors, “we showed that the combination of mesothelin and miR-103a-3p improved the diagnostic performance of a blood-based screening test, resulting in higher sensitivity and specificity to detect malignant mesothelioma.”

Malignant mesothelioma is a form of cancer that occurs in the thin layer of tissue that surrounds the lungs, abdomen and heart. Asbestos exposure in the only proven cause of mesothelioma.

Up to 3,000 new cases of the disease are diagnosed in the United States each year, with 85,000 U.S. cases expected until 2054.

Anyone who was exposed to asbestos in the past—or who worked in occupations at risk for exposure—should be aware of mesothelioma symptoms, which include chest or abdominal pain, shortness of breath, and unusual lumps in affected areas.

Because early diagnosis is the key to a favorable prognosis, schedule a doctor visit immediately if you have symptoms that might indicate mesothelioma.

Know more about Mesothelioma and how you can deal with it.

Sources :

biomarker
http://www.cancer.gov/dictionary?cdrid=45618
(new study published online by) PLUS ONE
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0114483

UK Mesothelioma Clinical Trial Tests for Mesothelioma Patients

Early Detection of Mesothelioma Could Someday be Possible Through Simple Urine Test

Researchers and physicians agree that the best way to combat cancer is to detect the disease at its earliest stage, when patients have the most treatment options available to them. Many cancers, including mesothelioma, however, do not have reliable, noninvasive screening methods. Now, researchers report success in detecting cancer through a simple urine test.

According to an article in MIT News, a team led by Sangeeta Bhatia, a member of MIT’s David H. Koch Institute for Integrative Cancer Research, has found a way to “amplify” cancer proteins to enhance the ability to detect them. Specifically, the researchers “developed nanoparticles that can home to a tumor and interact with cancer proteins to produce thousands of biomarkers, which can then be easily detected in the patient’s urine.”

Not only could this process be used to detect cancer, but it is also useful for monitoring disease progression and responsiveness to treatments.

Researchers at both MD Anderson Cancer Center and Massachusetts General Hospital Cancer Center are also in the early stages of developing a cancer detection tool using circulating tumor cells (CTCs). The tests must be highly sensitive to detect such few cells in the bloodstream. These tests, while still in the early phases of testing, can detect lung cancer as well as determine the efficacy of the treatment. The hope is that the tests may also be able to detect mesothelioma.

Although finding CTCs in the bloodstream has been likened to finding a needle in a haystack, the MIT researchers found a process to treat the nanoparticles so that they would accumulate at the tumor site. Hundreds of peptides are then released from the nanoparticles, flooding the bloodstream. They then rapidly accumulate in the kidneys where they are excreted in the urine, and are detected using mass spectrometry.

“There’s a desperate search for biomarkers, for early detection or disease prognosis, or looking at how the body responds to therapy,” says Bhatia.

This research “is an exciting approach to overcoming the problem of biomarker scarcity in the body,” says Sanjiv Gambhir, chairman of the Department of Radiology at Stanford University School of Medicine. Gambhir was not part of the research team.

Mesothelioma is a rare, serious cancer most often affecting the lining of the lungs that occurs in individuals exposed to airborne asbestos fibers. Diagnosing the disease is extremely difficult and many patients are not diagnosed until they exhibit life-threatening complications. Research of this type is needed to help prevent the nearly 3,000 Americans from dying of the disease each year.

Mesothelioma Metastasis Closer to Being Understood, Stopped

Researchers from the Massachusetts Institute of Technology report they have found the mechanism that allows cancer cells to break off the initial tumor site and spread to other parts of the body. Cancer cells are typically anchored in place, but understanding how they break free and migrate, the researchers believe, is the key to uncovering a new approach to cancer treatment.

The researchers report that metastasis is the cause of nearly 90 percent of cancer deaths. Pleural mesothelioma, a cancer of the lining of the lungs caused by past asbestos exposure, is one cancer that is highly aggressive and spreads quickly. The National Cancer Institute reports that treatments for patients with metastatic cancer are to control further growth of the cancer or to relieve symptoms caused by it. In some cases, metastatic cancer treatments may help prolong life. However, according to the NCI, most people who die of cancer die of metastatic disease. Understanding how to stop metastasis is critical for increasing survival in mesothelioma patients.

In a study published Oct. 9 in Nature Communications, MIT researchers reported that proteins called integrins, located on cell surfaces, form the anchors that hold the cells in place. But cells temporarily lose their ability to adhere as they become more metastatic, and the anchors “let go.” The freed cells then move to another area and regain their ability to adhere or stick to tissues, forming another tumor.

“If we can prevent them from growing at these new sites, we may be able to interfere with metastatic disease,” says Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science, and leader of the research team.

The authors of the study found that metastatic tumors stuck especially well to fibronectin and galectin-3 proteins that are made of proteins that contain or bind to sugars. This finding, they suggest, can lead to development of new anti-cancer drugs that focus on “a specific protein-protein or protein-sugar interaction, rather than a particular gene mutation.”

The research team is currently developing drugs aimed at inhibiting tumor cell interactions with galectin-3.

2,500 to 3,000 people are diagnosed with mesothelioma each year in the U.S. Mesothelioma takes decades to appear after exposure, but then advances rapidly.

Wake Forest Study Shows Treatment to Reduce Fluid Buildup in Patients with Peritoneal Mesothelioma

A new study from cancer researchers at North Carolina’s Wake Forest University reports that undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) can improve the lives of those suffering from peritoneal mesothelioma by controlling the buildup of fluid in the abdomen.

CRS/HIPEC Offers A More Permanent Solution To Fluid Build Up

The accumulation of fluid in the peritoneal cavity (the space between the lining of the abdomen and abdominal organs) can cause those with mesothelioma a great deal of discomfort. However, according to a recent article in the Annals of Surgical Oncology, undergoing CRS/HIPEC can offer a more permanent solution to fluid build up.

Left untreated, the building up of fluid can cause not only discomfort, but also bloating, disfiguration and shortness of breath as it interferes with diaphragm movement. Although peritoneal mesothelioma sufferers can have fluid drained, it generally accumulates again in time. So, how can treatment help?

Cancer researchers at Wake Forest University studied 299 patients, 15% of whom had peritoneal mesothelioma and the rest of whom had various types of primary cancers that had spread to the peritoneum.

All patients underwent cytoreductive surgery (CRS) to remove as much of the cancer as possible, followed by hyperthermic intraperitoneal chemotherapy (HIPEC). The procedure involves bathing the abdominal cavity in heated chemotherapy drugs to destroy residual cancer cells. According to the study, 93% of participants had a complete resolution of their ascites after a three-month period. This included some cases in which the cancer itself could not be completely removed.

Authors of the study, published in the Annals of Surgical Oncology, wrote that, “Although complete cytoreduction (the removal of cancerous cells) remains the goal of this procedure, HIPEC can provide palliative value in selected patients with malignant ascites.” This can improve the quality of life for mesothelioma patients, even in cases where it may not necessarily be able to improve survival rates.

Exposure To Asbestos Primary Cause Of Peritoneal Mesothelioma Peritoneal

mesothelioma accounts for 10 to 20 percent of the nearly 3,000 cases of mesothelioma diagnosed in the United States every year. The primary cause of peritoneal mesothelioma tumor is exposure to asbestos. Symptoms may include:

abdominal pain
anemia
blood clotting abnormalities
bowel obstruction
swelling due to a buildup of fluid in the abdomen (ascites)
weight loss.

If you’ve been exposed to asbestos, it’s important to see your healthcare professional immediately to determine whether you may have developed mesothelioma. Many mesothelioma victims were exposed to asbestos fibers and dust particles decades ago and far too many aren’t diagnosed until the cancer is in its later stages.

While life expectancy rates for untreated peritoneal mesothelioma are grim, early detection and effective treatment, such as CRS/HIPEC are available to combat symptoms and may improve prognosis.

NC State Research Could Lead to New Method of Treatment for Mesothelioma

The science around microRNAs is in the news again after North Carolina State University researchers report they have discovered a way to identify cancerous cells that could lead to “new methods of disease detection and treatment.” This comes on the heels of a fast-tracked Australian mesothelioma clinical trial that manipulates microRNAs to treat the cancer.

microRNAs, or miRNAs, are tiny molecules found within cells that serve a function in primary biological processes such as organ development, fat metabolism, cell proliferation and death. When miRNAs function properly, a person remains healthy. However, “disregulation” of miRNAs can lead to diseases, including mesothelioma and other cancers.

Directing Cancer Treatment Through microRNAs

Although other researchers have conducted basic DNA mathematical computations in test tubes, NC State researchers set out to attempt DNA-based logic computations to detect the presence of specific microRNAs in living human cells. According to a press release from NC State University, by performing these Boolean computations, when two miRNAs are present in a cell, the scientists could direct the output to release a “fluorescent molecule.”

In practice, however, instead of creating a glowing cell, “we could attach therapeutic agents that are released to treat the disease itself,” said NC State chemist Alex Deiters and co-author of the study.

When two conditions are met, as shown by the result of an “AND” Boolean computation when two specific miRNAs are present indicating cancer, the result could be “to release a drug that could kill a cancer cell,” said James Hemphill, Deiters’ graduate student and co-author of the study, according to the News & Observer.

How Can This Benefit Mesothelioma Patients?

Mesothelioma, the signature cancer of asbestos exposure, is difficult to treat due to its aggressive nature which often fights off even the strongest of medicines. Although chemotherapy is the primary treatment modality for the cancer, it has shown to be chemo-resistant at times, eventually rendering the treatments ineffective. One way oncologists can combat resistance to treatments is to target them specifically to the person’s unique genetic characteristics and the unique characteristics of the mesothelioma.

Ricki Lewis, PhD, geneticist and author of The Forever Fix, said in an email interview, “Cancer isn’t just one disease, it is many, and even within the same patient, a cancer’s characteristics change over time.”

http://blogs.plos.org/dnascience

One reason cancer is dynamic is because of microRNAs. “microRNAs orchestrate the turning off of certain genes as a cancer grows, invades, and spreads,” said Ms. Lewis. In fact, due to their intricate role in gene regulation, many leading scientists refer to miRNAs as the “master maestros of the genome.”

When asked about the importance of NC State’s study for mesothelioma, Ms. Lewis said, “Detecting patterns of microRNA deployment and tagging them to delivery of a treatment would be a rational and personalized way to treat mesothelioma.”

Targeting therapy for mesothelioma patients optimizes the potential for success of the treatment and offers mesothelioma treatment options that may not otherwise have been considered. Close to 3,000 Americans are diagnosed with mesothelioma each year. There is no cure for the disease.

The NC State study can be found in the June 24 issue of the Journal of the American Chemical Society.

http://pubs.acs.org/action/cookieAbsent

Category: Research