Mesothelioma Blog

The formation of a Central Institutional Review Board (CIRB) has shortened the process required to begin cancer clinical trials by a little over a month on average, according to a new study. The findings suggest that the CIRB is helping to streamline the timeframe of clinical trials from concept to completion – allowing for new technologies, procedures and drugs to hit the market sooner than previously possible.

The National Cancer Institute (NCI), a division of the National Institutes of Health (NIH), created the CIRB in 2001. Prior to the formation of this centralized review board, cancer research institutions funded by the NIH were required to use one of several independent IRBs for monitoring purposes.

Clinical trials are lengthy testing phases of new treatments. The goal of clinical trials is to verify the safety and effectiveness of new drugs and procedures to ensure their efficacy for public use. The process has been known to take up to ten years and cost up to $1 billion in some cases.

Though time-consuming, these clinical trials are seen as necessary precautions to ensure the safety of new emergent drugs. However, in an effort to expedite the procedure, the NCI initiated the formation of a centralized review board.

To determine if such an initiative was successful, scientists at the Veterans Affairs Palo Alto Health Care System and Stanford University School of Medicine compared CIRB trial reviews to those performed by unaffiliated local IRBs. Surveys were collected from both oncology research staff and IRB staff. These surveys were intended to identify differences in effort, timing and costs associated with the review process.

In addition to hastening the review process, the study determined that the centralized review board saved oncology researchers $717 per initial review.

The new study serves to validate all the hard work that went into organizing and maintaining the CIRB. As Dr. Jeffrey Abrams, associate director of the NCI’s Cancer Therapy Evaluation Program, suggests: “For all the volunteer reviewers and participating sites, this study provides objective confirmation that a centralized approach significantly improves the overall process for participants in multi-site trials.”

Now that CIRB benefits have been verified, researchers intend to initiate efforts to improve enrollment in the centralized review process. Presently, some sites may still opt to use independent review boards.

Resource: http://www.cancer.gov/newscenter/pressre…

The success rate of surgical procedures related to removal of cancer tumors is often directly tied to the surgeon’s ability to remove all cancerous cells found in the body’s tissue. Miss just one small patch of cancer, and the illness can regroup and regrow.

Now, new technology is helping oncologists sniff through body tissue mid-surgery to identify cancerous tissue so that it can be removed on the spot. The innovative instrumentation matches a mass spectrometer with an electroscalpel, and has the potential to greatly improve success rates of cancer surgery.

Mass spectrometry is a powerful technology that quickly categorizes molecules based on their ratios between mass and charge. Because cancer cells and healthy cells exhibit unique molecular profiles, mass spectrometry can be incredibly useful for surgical cancer procedures.

However, using this technology in the operating room has been hindered by the fact that mass spectrometry requires a collection of sample cells. These cells must be bombarded with charged particles in order to achieve ionization. To achieve ionization, gaseous procedures such as high-voltage nitrogen jetting are required. These procedures are not safe for the human body. Additionally, these ionized particles must be sucked into a machine for analysis.

Recently, an innovative workaround was developed to answer this problem. As it turns out, electroscalpels already produce gaseous ions. These ions, which serve as a waste product of the instrument’s function, are effective in propelling the necessary ionization to achieve mass spectrometry. Additionally, these fumes are already collected due to their hazardous nature.

The new collaboration of technologies was developed at Justus-Liebig University in Giessen, Germany and headed by Professor Zoltan Takats.

Because mass spectrometry can analyze tissue samples within a few hundred milliseconds, Takats explains, “we can draw a map and say this part is healthy liver, that is connective tissue, this is adipose tissue, that is cancer.”

The technology makes current surgical procedures seem antiquated in comparison. Today, surgeons use imaging scans taken pre-surgery, as well biopsy results, to guide surgical removal. However, if the surgeon happens upon suspicious tissue during the surgery, little could be done to verify or disprove the presence of cancer.

Mass spectrometry can also be useful for post-operative care. Mid-surgical profiling can produce accurate images of the tumor, which serve to map locations of the cancerous cells. This data can identify the progression of the tumor, which can be helpful when prescribing type and dosage of chemotherapy drugs.

Takats and his team have so far tested the advanced electroscalpel on lab rats and other animals. Clinical trials on humans are set to begin in the near future. If proven successful, one hurdle that may limit real-world applications is cost. An electrosurgery system coupled with a mass-spectrometry system currently costs about $128,000. However, Takats believes a lower performance model could be just as effective, and cost about $20,000.

Resource:
 http://www.technologyreview.com/biomedic…

More than one-third of all breast cancer patients are administered chemotherapy drugs that are not explicitly approved by the U.S. Food and Drug Administration (FDA) to treat the disease, according to a recent study conducted by M.D. Anderson.

Such a practice is relatively common among many illnesses, but it especially prevalent among breast cancer patients. Known as off-label drug use, doctors often prescribe drugs that are FDA-approved for the treatment of other conditions, but not breast cancer. The term “off-label” refers to the drug label report that is approved by the FDA. Such a report dictates approved doses and for which medical conditions the drug is considered a safe and effective treatment.

In terms of breast cancer, M.D. Anderson researchers found that 35 percent of women were treated with off-label chemotherapy drugs between the years of 1991 and 2002. This percentage was calculated by using the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) database. This database is considered the most extensive cancer registry in the United States, and represents 26 percent of the entire U.S. population.

All women in the study were aged 65 years or older. Researchers note that oncologists tend to treat older patients more conservatively. As such, the actual percentage of breast cancer patients using off-label medications may be higher than 35 percent.

The most prevalent off-label drug used to treat breast cancer was Navelbine® (used by 16 percent of all off-label breast cancer patients). Navelbine is a drug approved for the treatment of lung cancer. Gemzar® – a pancreatic cancer drug – was also a commonly prescribed off-label treatment.

Both chemo drugs have been shown to be effective in the treatment of breast cancer. However, clinical trials explicitly testing the safety and effectiveness of such drugs for use in breast cancer treatment have not been completed. Drugs that have been proven effective, but as of yet properly passed clinical trials, make up the majority of off-label drug cases.

However, some off-label drug use is considered hazardous or shows no signs of medical benefit. In fact, researchers found that seven percent of off-label breast cancer treatments were considered medically inappropriate.

Such off-label use raises controversy around the unrestricted use of FDA-approved drugs. Additionally, off-label use of chemo drugs is typically not approved by Medicare, Medicaid and insurance.

Resources: http://www.mdanderson.org/newsroom/cance…
 http://www.cancer.org/docroot/ETO/conten…

In recent years, research efforts related to the use of histone deacetylase (HDAC) inhibitors have yielded promising results in the field of cancer treatment. Within the coming years, experts predict this new class of anticancer agents will emerge to produce clinical benefits among various cancer treatment regiments. Further down the line, second-generation HDAC inhibitors may be improved to deliver personalized treatment methods.

The benefits of HDAC inhibitors are linked to their ability to augment tumor growth. Specifically, these inhibitors interfere with angiogenesis (growth of new blood vessels needed to feed tumors) and cell cycling. They also spur programmed cell death.

HDAC inhibitors are further heralded for their ability to boost the effectiveness of current cancer treatments.

Histone acetylases are enzymes associate with RNA synthesis. A number of HDAC inhibitors have been found to exhibit beneficial control of cancer cell transcription. Different HDAC inhibitors alter cellular functions in a variety of ways, from cell differentiation and apoptosis to cytoskeletal modifications. These multiple pathways for treatment serve to provide researchers with a vast number of research possibilities.

A small number of HDAC inhibitors have already entered experimental trials. For example, FK228 (depsipeptide) has been found to be an effective treatment for prostate cancer among mice. The general consensus is that such treatments are relatively safe, with primary symptoms that include reduced white blood cell production (neutropenia) and reduced presence of platelets (thrombocytopenia).

HDAC inhibitors have also shown treatment potential outside of the realm of cancer. Most notably, brain disorders such as Huntington’s disease, multiple sclerosis and Rett syndrome have emerged as disorders that may benefit from HDAC inhibition.

Resources:
 https://www.leaddiscovery.co.uk/reports/…
 http://www.ncbi.nlm.nih.gov/pubmed/11914…
 http://www.nature.com/nrd/journal/v7/n10…
 http://cat.inist.fr/?aModele=afficheN&am…

Significant increases in survival for neuroblastoma, a childhood cancer, have been achieved through the use of new antibody treatments, according to a British study based out of Southampton University.

The monoclonal antibodies, dubbed anti-41BB and anti-CD40, “super-charged” the immune systems to spur the eradication of cancerous neuroblastoma tumors in 40 to 60 percent of all laboratory tests.

When one of the antibodies was combined with a unique peptide (protein fragment), the results were similarly promising for more aggressive tumors.

The two antibodies are designed to bind with molecules in the immune system. Once attached, the antibody stimulates the production processes, causing the immune system to spring into action.

The study, while promising, is still in the very early stages of research. As Juliet Gray, leader of the Southampton study, states: “Although this work is still at a pre-clinical stage, we hope it has enabled us to identify a way that we can provide effective immunotherapy treatment against neuroblastoma.”

Neuroblastoma is a type of cancer that attacks the nervous system. Though rare, it is the most common type of cancer diagnosed in infants. Present chemotherapy treatment methods return a 60 percent success rate among patients diagnosed with the illness. It is hope that these new immunotherapy solutions may one day become a viable new treatment option.

Immunotherapy – the process bolstering the body’s immune system to better fight illness – has already proven successful in the treatment of adult cancers. Similar monoclonal antibodies are presently FDA-approved for medical treatment. Some of these include rituximab (Rituxan or MabThera) and alemtuzumab (Campath).

Next for the Southampton team is to research the safety and effectiveness of monoclonal antibodies in children. Studies will also be conducted to determine of immunotherapy can be used in conjunction with chemotherapy treatments.

Resources:
 http://www.reuters.com/article/latestCri…
 http://www.pharmacyeurope.net/default.as…

When it comes to identifying the causes of cancer, most researchers focus on environmental triggers and gene mutation. However, a new viewpoint comes from Paul Ewald, an evolutionary biologist at the University of Louisville at Kentucky. With his unique background, Ewald has applied Darwinian biology to the problem of cancer, and he believes viruses are the primary answer.

A handful of cancers have already been linked to viruses. For example, hepatitis B can cause liver cancer and the human papilloma virus can cause cervical cancer. However, Ewald believes that by the year 2050, we will have identified infections that cause as many as 95 percent of all cancers.

To verify this claim, Ewald points out that cancer requires “a few specific genes to be mutated, within a limited number of cell divisions, to cause the cells to divide uncontrollably.” A mutation of any of the other 30,000 genes results, not in cancer, but in cell death or similar crippling results. It has already been proven that both hepatitis B and human papilloma have evolved to specifically spur gene mutations associated with cancer.

Given the fact that random gene mutations are highly unlikely to target the correct genes, Ewald hypothesizes that unidentified infections are behind the majority of cancers. However, this does not mean that genetic defects or mutations do not contribute to cancer. Ewald states that “viruses push cells to the brink; additional mutations from genetic defects or the environment are needed for full-blown cancer.”

Sexually transmitted diseases and kissing diseases have the most potential to cause cancer, according to Ewald. This is due to the long-term low profile of these infections, which allows them to be passed on to multiple partners over the course of several years. Currently, almost all identified cancer-causing viruses fit into these categories.

Ewald believes that by targeting the evolution of viruses and other pathogens, healthcare costs could be cut by 80 percent in the future. This dramatic drop would largely be due to infection prevention measures that would ultimately halt the formation of cancer before it can manifest. Additionally, steps could be taken to ensure that, if you are infected with an identified virus, the probability of cancer can be minimized. Vaccines used to prevent cervical cancer and blood test screening for hepatitis B are current examples that such tactics work.

Resource:
 http://discovermagazine.com/2009/new-sci…

New DNA sequencing technology at the Brigham and Women’s Hospital (BWH) has identified several new unique genetic mutations in mesothelioma cancer cells that were previously unidentified.

The findings serve as promising evidence that the improved sensitivity and effectiveness of DNA sequencing technology is providing more pertinent and rapid results in relation to cancer gene profiling. Successful identification of over-expressed genes, for both mesothelioma and other types of cancer, can help dictate the best course of cancer treatment.

As lead author of the BWH study, David Sugarbaker, explains: “after spending a year and a half to develop the methodology and software for the pipeline, new tumors can be analyzed over the course of about a month. Knowing which genes are mutated opens the door to better understanding and the discovery of more targeted and effective patient-specific treatments in real time.”

In the initial mesothelioma analysis, tissue samples were taken from four patients with malignant pleural mesothelioma, one patient with lung cancer and one with normal lung tissue. All expressed genes from each sample were sequenced (numbered in the billions). With no preconceived notions of which genes may be indicators of mesothelioma, 15 new mutations were identified in the four mesothelioma tumor samples.

Moreover, it was found that each tumor had unique genetic mutations not shared by any other tumor sampled. This suggests that mesothelioma tumors are singularly unique, much like our fingerprints.

Ultimately, this study exhibits the promise of advancements in DNA sequencing technology. One day such technologies may be a standard procedure for all cancers used for the purpose of identifying tumor mutations and dictating treatment. As Fleisher envisions it: “every patient’s tumor will be directly sequenced to determine its mutations and optimal treatment just as we now identify the cause of an infection before selecting the best antibiotic to treat it.”

Resources: http://www.brighamandwomens.org/PressRel…

Personalized cancer care has been growing by leaps and bounds in the past few years. Frequently, new technologies and treatments are being developed to help oncologists sub-classify patients beyond general types of cancer and provide improved treatment on a case-by-case basis.

One of the newest technologies currently in development is a class of products known as microfluidics microchips. Such computer chips allow scientists to capture rare types of tumor cells and isolate minute gene expressions that could potentially help dictate viable treatment options.

Presently, such microchips are in clinical trials as a treatment aid for prostate cancer. The study, being conducted at the Genitourinary Oncology Service at Memorial Sloan-Kettering Cancer Center, will consist of prostate cancer patients that have responded poorly to other forms of treatment.

Through microchip analysis, a comprehensive genetic profile will be provided for each participant. As Martin Fleisher, chairman of Department of Clinical Studies at Sloan-Kettering, suggests: the goal of this gene analysis is to determine which “genes are over-expressed and whether or not [the participants] would be candidates for certain types of targeted therapies that would beat down their cancer.”

Gene profiling is currently used to dictate treatment regiments for several cancers. For example, Herceptin is typically only used on breast cancer patients that have a specific protein present in their tumors.

However, prior to microfluidics, doctors were required to obtain a biopsy to obtain a proper gene profile. Such a luxury is not always available. As a workaround, scientists have longed for a reliable way to identify and isolate the low concentrations of tumor cells present in the bloodstream. Sloan-Kettering’s microchip seems to be the solution.

The microfluid chip Sloan-Kettering is employing for the study is manufactured by Fluidigm. The technology is remarkably advanced, with the ability to filter DNA from each cell into one of 96 microscopic channels. Reagents entering from the opposite side combine with the cells to create 9,000 simultaneous reactions. These reactions indicate differences in gene expression, and serve to effectively profile cancer cells.

For the prostate cancer study, researchers will analyze approximately 30 key genes in each patient. Expression of these genes, many related to testosterone production and cell signaling, have previously responded well to dasatinib in animal models. Dasatinib is a chemotherapy drug that is currently used to treat chronic myelogenous leukemia.

Once the most promising candidates for the drug have been identified through microfluidics, clinical trials will be initiated to test the predictive effectiveness of this burgeoning technology.

Resource: http://www.technologyreview.com/biomedic…

New DNA sequencing technology at the Brigham and Women’s Hospital (BWH) has identified several new unique genetic mutations in mesothelioma cancer cells that were previously unidentified.

The findings serve as promising evidence that the improved sensitivity and effectiveness of DNA sequencing technology is providing more pertinent and rapid results in relation to cancer gene profiling. Successful identification of over-expressed genes, for both mesothelioma and other types of cancer, can help dictate the best course of cancer treatment.

As lead author of the BWH study, David Sugarbaker, explains: “after spending a year and a half to develop the methodology and software for the pipeline, new tumors can be analyzed over the course of about a month. Knowing which genes are mutated opens the door to better understanding and the discovery of more targeted and effective patient-specific treatments in real time.”

In the initial mesothelioma analysis, tissue samples were taken from four patients with malignant pleural mesothelioma, one patient with lung cancer and one with normal lung tissue. All expressed genes from each sample were sequenced (numbered in the billions). With no preconceived notions of which genes may be indicators of mesothelioma, 15 new mutations were identified in the four mesothelioma tumor samples.

Moreover, it was found that each tumor had unique genetic mutations not shared by any other tumor sampled. This suggests that mesothelioma tumors are singularly unique, much like our fingerprints.

Ultimately, this study exhibits the promise of advancements in DNA sequencing technology. One day such technologies may be a standard procedure for all cancers used for the purpose of identifying tumor mutations and dictating treatment. As Fleisher envisions it: “every patient’s tumor will be directly sequenced to determine its mutations and optimal treatment just as we now identify the cause of an infection before selecting the best antibiotic to treat it.”

Resources: http://www.brighamandwomens.org/PressRel…

President Obama announced plans to contribute $5 billion in medical research grants that the White House says will cumulatively provide “cutting-edge medical research in every state across America.”

The funds will be provided via Obama’s $787 billion economic stimulus plan, and will largely be used to aid research into cancer, heart disease and autism.

The president made the announcement while visiting the National institutes for Health on September 30. As he puts it, the goal of this stimulus package is “to unlock treatments to diseases that have long plagued humanity, to save and enrich the lives of people all over the world.” Obama also noted that this is the “single largest boost to biomedical research in history.”

One billion dollars of the package will be set aside for cancer research geared towards understanding genetic causes associated with cancer and improving personalized treatment mechanisms. To facilitate this goal, $175 million has already been set aside for grants devoted to the Cancer Genome Atlas.

The Cancer Genome Atlas is an initiative currently underway to extensively map the unique genetic changes that affect cancer. Specifically, the money will be used to collect tens of thousands of cancerous tissue samples and subsequently sequence the entire DNA strands of over 20 forms of cancer.

President Obama stresses that the more than 12,000 grant awards will largely take place at not-for-profit institutions such as the National Institutes for Health. By eliminating profit incentives, the president hopes to spur unbiased research.

Beyond touting the potential for significant advancements in the study of cancer and other medical ailments, Mr. Obama noted that the $5 billion package will serve to “create new jobs, tens of thousands of jobs” for medical workers, researchers, educators and medical equipment manufacturers.

Along with discussing the stimulus package, Obama highlighted the importance of his health care reform package. As he puts it, all the medical advancements achieved through the package “make no difference to the family that is dropped from an insurance policy when a child gets sick.”