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Nanoparticles Could be Used to Improve Cancer Treatment, Diagnosis

Nanoparticles are finding early success in fighting the war on cancer. At Burnham Institute for Medical Research in La Jolla, CA, researchers have shown how anticancer nanoparticles can be used to improve MRI imaging of tumors and improve the dissemination of cancer drugs directly to the site of cancer.

These beneficial results are due the ability of anticancer nanoparticles to flock directly to a tumor and subsequently attract additional nanoparticles to the site. As a result, this advanced accumulation has been shown to deliver larger quantities of MRI image-enhancement agents to the point of illness so that improved diagnostics can be achieved.

In a similar fashion, nanoparticles may also be used to magnify the amount of chemotherapy drugs that actually penetrate into a tumor.

These findings are reported on the heels of Burnham lab tests that involved using nanoparticles to diagnose mice with breast cancer tumors. The team reports MRI imaging that was three times brighter than offered by conventional methods – a fact that greatly improves diagnosis potential.

In addition to their homing capabilities, nanoparticles provide a secondary benefit that helps starve a tumor of oxygen. Through tests with the mice, the team reports that 20 percent of blood vessels inside the tumor became blocked due to clotting. Such a fact could significantly diminish the growth rate of tumors.

In terms of drug administration, nanoparticles could not only increase the benefits of chemotherapy, but also diminish side effects. This is due to the fact that a higher proportion of the drugs find their way into the invading tumor as opposed to healthy tissue.

Findings reported by the Burnham Institute team were published in a recent edition of the Proceedings of the National Academy of Sciences.


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New Diagnostic Technique Could Result in Test for Mesothelioma

Reuters is reporting a new blood test that could identify mesothelioma at an early stage. The biotech company Somalogic, which specializes in developing diagnostic tests, announced a new technology that could allow doctors to identify mesothelioma in patients before they show visible symptoms.

Somalogic scientists used blood samples from mesothelioma patients and were able to develop aptameters (oligonucleic acid or peptide molecules) that bind to proteins expressed by mesothelioma cells. These biomarkers are present in the blood at extremely low concentrations, so conventional chemical analysis cannot find them. The use of proteomics array technology and genetic material specific to the protein allows discovery of the disease early in its development.

According to HealthDay News, Somalogic scientists identified 19 biomarkers for mesothelioma. They found a specificity of 100% for those markets. Sensitivity was 80%. If these numbers hold through further development, the diagnostic process would be able to identify the large majority of mesothelioma cases with some false positives.

If this technology proves reliable it could be used in a screening process for people with a history of asbestos exposure. Asbestos is known to cause mesothelioma, but the latency period is very long and the symptoms often don’t manifest until the disease has progressed to a point at which treatment options are limited. Early discovery of mesothelioma would give doctors and patients more options and improve the prognosis of those afflicted with this cancer.


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Cancer Stem Cells More Complex Than Previously Thought

Studies into cancer stem cells and how they might be targeted for cancer treatment have been fervent over the past ten years. Indeed, there is a lot of evidence that suggests these unique cancer cells may lead to significant breakthroughs in treatment. However, as more and more research is being put into stem cells, researchers are discovering that the path to successful drug development may be more complex than initially thought.

Like healthy stem cells, cancer stem cells serve as progenitors (at least that’s the theory). As progenitors, these cells are responsible for re-growing tumor cells following cancer-killing treatments such as chemotherapy. Clearly, finding drugs or treatments that diminish the effects of these stem cells could help improve cancer survival rates.

In the past, researchers believed that all cancers followed a cancer stem cell model. This model suggests that such cells initiate the growth of cancer tumors. However, such a belief is changing as more research suggests a number of different cell types may instigate tumor growth.

While early cancers linked to stem cell tumor growth – such as acute myeloid leukemia and other blood cancers – continue to show a string linkage, there have been mixed research results for other types of cancer. As Dr. Jean Wang of the University of Toronto explains, “most of the markers we have right now are still very rough.” While many of these markers suggest stem cell growth in such cancers as brain, breast, colon and pancreatic cancer, there is enough variation in studies to result in skepticism among some experts. In fact, according to Dr. Barbara Vonderhaar of the NCI Center for Cancer Research, “We still don’t have definitive proof that cancer stem cells exist.”

As such, the initial goal for cancer stem cell research is to clearly validate their presence and importance in tumor growth. Until this happens, it will be extremely difficult (and possibility even futile) to attempt to create cancer drugs that target these progenitors.


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Smallpox and Other Viruses Hijacked to Help Fight Cancer

In 1796, Edward Jenner showed that the cowpox virus could be used to inoculate people against smallpox. Today, the same vaccine is being looked at as a potential treatment against cancer. Vaccinia poxvirus is just one of several viruses that has been hijacked for the purpose of killing cancer tumors (herpesvirus is another high profile enlistee). These viruses, known as oncolytic viruses, are currently in late-stage human testing and have shown remarkable promise.

Through genetic engineering, such oncolytic viruses have been altered slightly to specifically seek out and attack cancer cells. Upon infection, the virus replicates and continues to infect new cancer cells, often killing them. To bolster cell death of the cancer, many engineered viruses also include an immune system protein (GM-CSF) that serves to boost the natural response of the individual’s immune system. The inclusion of this protein attracts white blood cells to mount a two-front attack on the cancer cells.

Cancer patients need not worry about the altered viruses infecting healthy cells. In the case of vaccinia poxvirus, the genetic engineers have removed a gene known as thymidine kinase. This gene is necessary for replication within the body.

The vaccinia virus is showing early promise in its effectiveness against a variety of cancers. In a phase II clinical trial, 18 of 24 patients diagnosed with liver cancer survived for a minimum of 12 months. In comparison, roughly half of liver cancer patients typically survive to the one-year mark. A phase III clinical trial is scheduled to begin later in the year.

An early-stage trial has also tested the engineered virus against colorectal, ovarian, skin and lung cancers.

In these early studies, patients reported flu-like symptoms to the treatment. However, no other major side effects were reported. Individuals who have previously received a smallpox vaccine showed no reduction in benefits.

Beyond the vaccinia virus, an engineered herpesvirus known as OncoVex is showing promise against head and neck cancer. The treatment is currently in phase III clinical trials. A nearly identical virus has already met approval in China and is currently available.

If these new cancer treatments eventually make it to market, they will almost certainly be paired with chemotherapy or radiation. Treatment studies focused wholly on virus treatment have not been nearly as successful as those that incorporate a combination of virus therapy and chemo or radiation.


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Palliative Care for Lung Cancer Improves Length, Quality of Life

New research suggests palliative care may not only ease suffering of lung cancer patients, but also increase lifespan. This insight comes on the heels of a study of 151 patients with advanced lung cancer. Among these patients, those that were given early palliative care typically been reserved for patients close to death were shown to survive 2.7 months longer than those who received standard care.

This extended lifespan occurred despite a less aggressive cancer treatment regiment that included less frequent sessions of chemotherapy. As such, the findings suggest that drug therapy is not the only important element to consider when providing cancer treatment.

Palliative care is a type of treatment that focuses on minimizing a patient’s symptoms, as well as improving mental health and quality of life. In some cases, patients may be reluctant to choose palliative care, as many associate it with “giving up” on fighting the disease.

However, as this new study suggests, such is not necessarily the case. Thomas Smith, a palliative care expert who runs a program at Virginia Commonwealth University refers to the study as a breakthrough ñ serving to highlight the importance of beginning palliative care sooner rather than later.

Though overall cancer treatment is less intensive with a palliative care focus, the whole-health approach requires the involvement of numerous nurses, doctors, nutritionists, pharmacists and others. As a result, patients receiving palliative care are commonly able to minimize in-patient hospital visits.

As Dr. Ira Byock ñ an expert at Dartmouth Medical School who was not involved in the study ñ sums up, “Attending to people’s physical, emotional, social and even spiritual well-being is good for them and helps them live longer.”


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Turning Cancer Into a Mathematical Formula

What do computer engineers, physicists and mathematicians have to offer in the fight against cancer? As it turns out, quite a lot. In a new collaboration that finds these non-medical professionals teaming up with oncologists, these new enlistees in the war on cancer have been tasked with turning the disease into a mathematical formula.

Working at twelve locations set up by the National Cancer Institute (NCI), several small teams of oncologists and computer engineers are working together to mathematically define how cancer grows and spreads throughout the body.

At one such worksite located at the University of Southern California, computer architect Danny Hillis and oncologist David Agus are collaborating to create a comprehensive model of lymphoma. The ultimate goal of their work is to create a series of interlocking computational models that successfully predict various aspects of the disease and allow for personalized therapy.

In other words, the team is working to create a ‘theory of lymphoma,’ much in the same way that Newton created the theory of gravity. With these hard-set facts in place, the USC team hopes to produce a model that allows doctors to predict patient response rate to various combinations of therapy based on such parameters as age, sex, blood pressure and specific genetic sequences.

This formulaic approach is intended to fine-tune personalized therapy so that each individual patient receives the treatment most likely to deliver positive results.

The burgeoning technique is similar to previous personalized medical research practices. However, instead of simply looking at one gene or antibody, the computer model is intended to take everything about a disease into account. Within five years, the USC team hopes to have a thorough computational model of mouse lymphoma. The insights learned from this model will then be extended towards human applications.


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Personalized Genetic Profile of Cancer Now Available to Public

A startup company known as Foundation Medicine has just been launched with the primary goal of offering personalized genetic profiles of cancer genomes. The initiative is the first such available service, and aims to help cancer patients receive targeted cancer treatment.

In recent years, doctors and researchers have come to realize the value of mapping for specific cancer mutations. For example, a specific cancer mutation that is associated with breast cancer (HER2) has been known to seriously diminish the success rate of traditional breast cancer treatments. For these patients, the use of Herceptin within the treatment regimen helps overcome HER2 to increase survival rates.

While a handful of identified genes such as HER2 are routinely screened for when diagnosing cancer, a complete genetic mutation analysis can reveal a number of other pertinent genetic mutation combinations. Foundation Medicine wants to make such information available through their targeted genetic analysis. The cost of such testing for a patient is estimated in the low thousands.

Newly formed in 2009, Foundation Medicine has already received support from a number of leading cancer and genomics researchers. The company, based in Cambridge, MA, recently raised $25 million in capital thanks to the venture capital firm Third Rock Ventures.

Initially, the Foundation genetic service will look at 100 genes that have been proven scientifically to affect the effectiveness of cancer treatment. Recently, an increasing amount of new drugs have been identified that specifically target some of these genes (such as Herceptin). In other cases, a specific gene may indicate that a certain treatment is not likely to work. In either case, knowing which of these 100 mutations a patient has or doesn’t have may significantly alter the success rate of cancer treatment.

As the scientific community continues to discover new critical genes, Foundation Medicine plans to update their service to provide up-to-date analysis. The company also plans to expand the analysis to include the chemical makeup of each individual cancer as well.

Mathew Meyerson, a leading genetics authority at Harvard Medical School and founder of Foundation Medicine, states, “a relatively comprehensive picture of the cancer genome is probably the best way to get a good understanding of what is the right diagnostic and the right treatment for the patient.”

In terms of timing, Foundation Medicine might seem by some to be a little early in providing such a service. Though the idea of personalized medicine is still rather new, the Cancer Genome Atlas Project is scheduled to finish mapping several thousand genes for each major type of cancer in the next couple of years. When complete, Foundation will be in a good place to take the data from the Atlas Project and quickly apply it to the real world.



Improving Adoption Rates of Orphan Drugs for Mesothelioma and Other Rare Diseases

Recently, research on a promising drug for a disease that currently affects 1,500 people in the United States annually was halted due the financial reasons, according to Peter Saltonstall of the National Organization for Rare Diseases. The root of these financial reasons stems from the cost of research versus the expected amount of profits that the pharmaceutical company can expect over the long term.

Saltonstall declines to name the particular illness in question, but the identity is hardly important. Such financial issues have long been a difficulty when it comes to spurring interest in research for virtually all rare diseases. Sadly, drug development is a profit-driven business – a fact that has long proven detrimental to “small potatoes” illnesses that affect less than 200,000 people annually. However, it should be noted that combined, more than 7,000 rare diseases affect 20 to 30 million people in the United States each year.

In an effort to improve interest in such research, the United States passed the Orphan Drug Act (ODA) in 1983. The ODA serves to increase incentives for pharmaceutical companies to pursue research within the rare disease sector. Such incentives include federally funded grants, tax credits on costs associated with clinical trials and a 7-year exclusive marketability of any drugs that eventually come to market.

In a lot of ways, the ODA has been very successful. Since 1983, the FDA has approved 357 rare-disease drugs. Additionally, 2,100 products entered the testing pipeline. In comparison, only 10 drugs for rare disease achieved FDA-approval prior to the Act.

However, many experts on the subject claim additional measures need to be taken. The Food and Drug Administration’s Office of Orphan Products Designation is responsible for reviewing studies that may or may not be eligible for orphan status. According to Tom Cote, who heads the department, “[Pharmaceutical companies] frequently come out with press releases saying how important orphan products are to them…[but] they infrequently pass anything substantive over my desk.”

In an effort to further bolster interest in rare diseases, a 2010 appropriations bill is calling for a review process for orphan drugs. The review may result in additional measures that can decrease the cost of cancer research for rare illnesses. For example, initiating statistical models that require fewer patient participants may drop research costs significantly. Of course, the concern is that shallower pools of data may reduce the efficacy of results. Still, Cote is willing to be flexible when it comes to spurring initial research.

As a complement to the proposed revisions, the FDA is already attempting to spur interest by holding on-site workshops that help provide guidance for maximizing current ODA incentives. Hopefully, these and other measures will result in a renewed interest in research for rare diseases.