Sarcomatoid Mesothelioma Treatment

Sarcomatoid mesothelioma is the least common histological type of mesothelioma, but it is the most aggressive.

http://www.ncbi.nlm.nih.gov/pubmed/20081811?dopt=Abstract

Even more than epithelial mesothelioma, the sarcomatoid form is difficult to diagnose and to distinguish from other diseases. Just looking at the cells under a microscope is not enough, and doctors employ immunohistological tests to distinguish Sarcomatoid mesothelioma from true sarcoma and pulmonary sarcomatoid carcinoma.

 

http://www.ncbi.nlm.nih.gov/pubmed/18199156?dopt=Abstract

The general treatment plan for sarcomatoid mesothelioma focuses on:

  • Managing pleural effusions
  • Administering radiotherapy to intervention sites
  • Evaluating suitability for radical surgery
  • Evaluating suitability for chemotherapy and clinical trial entry

Lung Cancer Patients Get Unequal Treatment

A new study from the MD Anderson Cancer Center in Houston found that patients who go to public hospitals for lung cancer care get less effective treatments than those who go to expensive cancer-oriented hospitals. The study also showed that patients who receive their care from public hospitals were nine times more likely to have severe symptoms when they check in for treatment than those who attend cancer centers such as MD Anderson.

The study examined the care in two Houston public hospitals, one Miami public hospital, and MD Anderson, one of the most respected cancer care centers in the world. Dr. Charles Cleeland, the study’s author, said that the disparity of care between public hospitals and cancer centers has existed “for the last couple of decades”. He also noted that lung cancer care “is less well managed” for patients who are poor, unemployed, members of minority groups or those that have little to no health insurance.

The number of public hospital patients experiencing symptoms before admitting themselves for care was nearly double that of cancer center patients. The study, which followed the patients’ progress for two months, showed major differences in the quality of care between the cancer center and the public hospitals. Dr. Cleeland said that patients in public hospitals that were displaying symptoms were “not being corrected”.

Dr. Cleeland also noted that the reasons for the differences in care between public hospitals and well-known cancer centers are “very complex”. “I don’t think it’s the intention of those caring for those folks,” he said. However, he did cite that the lack of access to technical resources or cancer specialists for those underserved patients might be some of the reasons behind the disparity.

A similar study conducted at the University of North Carolina found that African Americans are less likely than Caucasian patients to opt for surgery to remove lung tumors. Surgical tumor removal is often the most effective treatment in the early stages of the disease. Dr. Samuel Cykert, the UNC study’s author, attributed the differences to “unintended biases in physicians”. Dr. Cykert mentioned that doctors who work with underserved patients “would be less apt to recommend surgery” than they would for patients who could afford the procedure.

“Advocating for oneself is very important,” Dr. Cykert said. “Being passive is bad.”

The two doctors do agree on treating symptoms early, rather than allowing them to worsen before seeking help. Dr. Cleeland stressed that doctors, nurses and other health care professionals need to help patients with the symptoms of their lung cancer as much as with treating the cancer itself.

“I think we need to strategize about how to help them (underserved patients)”, he said. “This (study) is characterizing their experience.”

According to public health officials, 62 out of every 100,000 adults will be diagnosed with lung cancer each year. Underserved patients are more likely to engage in cigarette smoking, the primary cause of lung cancer in America, and are also more likely to die from lung cancer.

Sources:
http://www.reuters.com/article/2011/06/20/us-lung-cancer-patients-idUSTRE75J6Y320110620

Nanoparticles Communicate to Deliver Chemotherapy Drugs

Teams of researchers at opposite ends of the country have recently developed an improved system to deliver chemotherapy drugs to attack malignant cells. Scientists at both the Massachusetts Institute of Technology and the University of California at Sand Diego have devised a method involving microscopic machines known as nanoparticles. Although cancer researchers have used nanoparticles for several years to deliver chemotherapy treatments, this new method employs an added layer of accuracy.

While some cancer-fighting efforts with nanoparticles involve a single nanoparticle, the cooperative effort at MIT and UCSD involves a two-stage delivery system.  The first stage acts as a “scout”, locating the cancerous cells by tracking their protein emissions, which differ from those of health cells. Once the scout particle locates an area of malignant activity, it sends a signal to the second-stage nanoparticles. The second-stage particles deliver the chemotherapy drug and shrink the tumor.

Most methods that use nanoparticles to administer chemotherapy drugs are highly inefficient, with only one percent of the injected medication reaching the target. In tests on laboratory mice, the scientists found that the two-stage system delivered the drugs at 40 times the rate found in most single-stage methods. Geoffrey von Maltzahn, the lead author of the paper on this method, said that the dual-stage method “can improve the efficiency with which (nanoparticles) find and treat diseases like cancer.”

One of the keys to the success of the dual-stage system is that the “scout” particles are actually rod-shaped, microscopic gold particles. In addition to its connotations of wealth, gold is also highly conductive to both heat and electricity. When researchers shone a bright light on areas affected by the gold nanoparticles, the gold heated up and damaged the blood vessels around the tumor.

As the tumor began to bleed, the body sent a signal to its blood-clotting agents to create a protein known as fibrin. The second-stage nanoparticles also picked up on that signal and sent the drug to the bleeding tumor. The particles followed the signal deployed the drug to the tumor site. The blood clot closed around the malignant cells and sealed in the drug. This method improved both the accuracy and efficacy of the drug delivery system.

The method has shown great promise in the laboratory, as it improves the concentration of drugs delivered to the tumor site while greatly reducing the side effects associated with conventional chemotherapy treatments. However, much more research and effort will need to be done to see if it can be applied to human patients. One problem could be that the system could create blood clots in other areas of the body away from the tumor. Blood clots in the brain are often the source of strokes, and clots in the heart can cause pulmonary embolism and death.

“If you’re going to trigger coagulation, you want to be very selective, so that you don’t cause damage in other parts of the body,” said Dr. Anil Sood, an oncology specialist at the MD Anderson Cancer Center in Houston.

Related article

Sources:
http://www.popsci.com/science/article/2011-06/nanoparticle-teams-communicate-inside-body-target-tumors
http://blogs.discovermagazine.com/80beats/2011/06/21/two-types-of-nanoparticles-work-together-to-target-tumors/
http://bostinnovation.com/2011/06/21/mit-creates-new-nanoparticle-method-to-target-cancer-cells-more-effectively/
http://web.mit.edu/newsoffice/2011/swarming-nanoparticles-0620.html



Personalized Vaccines May Help Fight Cancer

Individualized vaccines created from a patient’s own cancer tumor may help boost the immune system’s response to the illness, according to a study conducted at Dartmouth-Hitchcock Medical Center. Early trials of the innovative new treatment option suggest that patient survival can be greatly improved through such vaccinations.

For the study, researchers (led by Richard Barth Jr, chief of general surgery at Dartmouth-Hitchcock) used dendritic cells culled from a patient’s blood to develop a personalized vaccine. Dendritic cells are an integral part of the immune system that seek out hostile antigens. By programming these dendritic cells to target a patient’s unique cancer cell manifestation, the result is an induced immune response to tumors.

As witnessed in the study, the injection of such a vaccine resulted in an effective anti-tumor response in a majority of patients.

The study included 26 patients who had tumors that had spread from the colon to the liver. All patients were surgically treated to remove the tumors. However, metastasized colon tumors are notorious for spawning regrowth following surgery. In an attempt to reduce the chances for the cancer to return, Barth and associates injected the vaccine into patients one month after surgery.

Study representatives report that 60 percent of all patients who received a vaccination displayed a favorable T-cell immune response to their tumors. Of those with a favorable response, 63 percent were alive and free of any signs of cancer after five years of treatment.

In comparison, only 18 percent of patients who did not respond to the immunization were alive and free of cancer during the same time period.

The study shows for the first time that dendritic vaccines may be useful in the treatment of cancer. Previous research efforts have attempted to show that such vaccines may be helpful in fighting larger tumor deposits. While previously unsuccessful, the vaccines may be used in conjunction with surgery to improve a patient’s chances for survival.

Additional studies are required before the efficacy and effectiveness of the treatment option can be validated. According to Barth, “This study isn’t definitive enough for us to say that everyone with colon cancer that spreads to the liver should get the vaccine. A next possible step would be to compare this vaccine with just dendritic cells which have not been pulsed with tumor antigens as a control.”

Findings of the study were published in the November issue of Clinical Cancer Research.

Sources:
http://www.smartplanet.com/business/blog/smart-takes/a-personalized-vaccine-to-combat-cancers-tumors/12609/
http://thedartmouth.com/2010/11/29/news/cancer


Vaccine Stops Cancer Before It Starts

The biotechnology company OncoPep is developing a vaccine against a deadly form of cancer before it becomes evident in patients at risk to contract the disease.  The vaccine is designed to prevent the onset of multiple myeloma, a type of cancer that attacks the bone marrow and forms tumors inside the bone.  The disease also strikes the immune system, increasing the production of antibodies and leading to pain and excess bleeding.

The vaccine represents a new step in the growing field of immunotherapy. Scientists who research immunotherapy treatments for various cancers develop methods for the body’s own immune system to combat cancer.  Immunotherapy research had led to the creation of vaccines that can prevent cancer, such as the human papillomavirus (HPV) vaccine that prevents cervical cancer in women. The field has also produced vaccines by programming antibodies to fight cancer as they would fight infections or other diseases.

The myeloma vaccine fits in an intermediate stage in cancer treatment. The primary treatment group would consist of patients who have a preliminary, pre-cancer stage of the disease, known as smoldering multiple myeloma (SMM).  Patients with SMM have abnormal growth rates in the plasma cells that create antibodies, but do not have the tumors and other symptoms that come with the full onset of the disease.

A team of researchers at the Dana Farber Cancer Institute in Boston developed a method to administer a vaccine made up of a mix of protein molecules called peptides.  The peptides contain protein molecules that myeloma tumors require for sustained life and growth.  As the antibodies attack the peptides, they also attack the myeloma cells. The immune system then robs the cancer cells of the proteins they need to survive.

Just as with blood types, doctors have classified patients into different types of immune systems, called “human leukocyte antigen (HLA) types”.  Doctors commonly use HLA typing to match donors and recipients in bone marrow transplants.  Researchers on the myeloma vaccine will target the treatment at patients with the most common HLA type, known as HLA type A2. Doris Peterkin, CEO of OncoPep, said that the peptides were more likely to trigger the needed antibodies in patience with the most common HLA type, and would be more effective in preventing SMM from becoming full myeloma.

As promising as the preliminary results have been, the road to a vaccine for multiple myeloma is still a long one.  Although patients with SMM develop full myeloma in almost 80 percent of all cases, only 10 percent of those cases progress to that stage each year.  OncoPep and the research team will still need to collect data for several years on the effectiveness of the vaccine before it will be ready for the wider marketplace.

Dr. Kenneth Anderson, one of the research team leaders who developed the vaccine, said that he hopes it could be used as a preventative measure for patients with SMM, who currently do not have treatment options available until the disease becomes full-blown myeloma.  “The idea (behind the vaccine) would be to prevent the development of an active cancer, ” Dr. Anderson said.

Sources:
http://www.technologyreview.com/printer_friendly_article.aspx?id=37520
http://www.fiercevaccines.com/story/oncopep-vax-aims-stop-multiple-meyloma-it-starts/2011-05-05
http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001609/

Breast Cancer Drug May Help Fight Lung Cancer

A new study from researchers at the University of Geneva shows that the breast cancer drug Tamoxifen may also be useful in combating lung cancer. The study found that women who were undergoing treatment for breast cancer, with Tamoxifen as part of their chemotherapy routines, also showed a reduced death rate from lung cancer. The research team examined data from women who received Tamoxifen from 1980 to 2003 and found that the death rate from lung cancer in those patients was eighty-seven percent lower than those who did not take the drug.

Tamoxifen has been used for decades to suppress the production of estrogen, a female sex hormone. Previous research efforts have tied the production of estrogen to breast cancer. Recent studies have also linked hormone replacement therapy, often prescribed to post-menopausal women, to an increased incidence of lung cancer. One of the premises of the Geneva study was to learn if suppressing hormones could be used as a therapy to treat lung cancer.

The study data did not show a decrease rate in the appearance of lung cancer in women who took Tamoxifen, but the results did show a remarkable reduction in the mortality rate from the disease. Dr. Elisabetta Rapiti, the study’s team leader, said that the data shows clear signs, “that there is a hormonal influence on lung cancer”. She also cited earlier findings that showed that lung cancer cells have receptors for estrogen and progesterone, another female sex hormone, which suggests that the mutated cells could feed off the hormones.

Oliver Childs, the senior science information officer at the British research facility Cancer Research UK, told reporters that it was “possible” that Tamoxifen and other anti-estrogen drugs could also have a positive effect on lung cancer patients. However, he also said that the results from the Geneva study were inconclusive since “the number of women who developed lung cancer (in the study) was small”.

In Dr. Rapiti’s study, out of more than six thousand patient records examined, only forty of the women showed signs of lung cancer. Less than half of the Geneva study patients underwent treatment with Tamoxifen or other hormone suppressants, and only one-third of the patients had ever smoked. The study data shows that nearly as many smokers used Tamoxifen as underwent other kinds of chemotherapy for their breast cancer.

The study authors also mentioned that the data was incomplete in places, including how the breast cancer diagnosis affected the women’s smoking behaviors. They also mentioned that they often lacked specific information on the types and dosages of anti-estrogen therapies the women received during their chemotherapy treatments.

Mr. Childs said that “large-scale clinical trials” would be necessary to determine how Tamoxifen could be used as a potential weapon against lung cancer. Dr. Rapiti also mentioned “prospective studies” to examine the findings further. She also said that, if any new studies confirm the earlier findings, it “could have substantial implications for clinical practice” in the treatment of lung cancer.

Sources: http://www.bbc.co.uk/news/health-12243206 http://www.medpagetoday.com/HematologyOncology/LungCancer/24487 http://www.financialexpress.com/news/Breast-cancer-drug-may-also-cut-lung-cancer-deaths–Study/741687/

Scientists Attempt to Widen Range of Targeted Cancer Drugs

The development of new chemotherapy drugs that target cancerous tumor cells – while leaving healthy cells alone – has been a breakthrough in the cancer treatment field. However, these treatments have been shown to work only on a select few patients. Even when they do work, the tumor can create a resistance to the drugs, leaving the patient with fewer options. Several scientific research teams are working on new drugs that will work with a wider range of patients and target tumors before they can develop a resistance to the treatments.

The main component in the research behind these new cancer drugs comes from a deeper knowledge of how cancer cells come into being, grow, multiply and spread throughout the body.  One study at the Massachusetts Institute of Technology examines lung cancer cells and how scientists can synthesize drugs that can target the tumors.  The treatments can also be modified to help the patient as they proceed through the chemotherapy routines.

The MIT study takes a close look at a class of drugs known as “epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors”. Tyrosine kinase is a protein that functions as an “on/off” switch for many cell functions. When the proteins that regulate cell growth are permanently set in the “on” position, the cells can grow quickly and in uncontrolled ways, a common occurrence in cancer cells. Tyrosine kinase inhibitors act to slow down or stop the wild cell growth and stabilize or reduce the size of lung cancer tumors.

EGFR inhibitors are effective in less than 40 percent of all lung cancer patients. The drug’s effectiveness varies widely based on the patient’s medical history, smoking habits, race, gender and ethnicity. Dr. Philip Sharp, Professor at the Koch Institute for Integrative Cancer Research at MIT, said that laboratories around the world have “hundreds of drugs” that are in various stages of testing and development. “To personalize cancer care, we must interpret changes in (tumors) to predict the correct drug combination to use.”

Another factor in customizing cancer treatments is that some patients carry a mutation in the gene for EGFR, which makes the drugs more effective. The MIT study examined the differences between those patients and patients that did not respond to the drug. MIT researcher Doug Lauffenburger, along with a team of researchers, developed mathematical models to simulate the behavior of different types of cancer cells. The models revealed that the cancer cells that responded to the drug had a slower uptake of EGFR than the less responsive tumors.

While these methods require further verification, scientists are hopeful that the findings can lead to a possible screening test for lung cancer patients to determine the effectiveness of EGFR inhibitors in individual cases. Lauffenburger and his team also learned that the EGFR inhibitors could be more effective in certain cases when combined with another class of chemotherapy drug known as MEK inhibitors, which are often used to treat melanoma. In terms of tailoring drug combinations to individual patients, Dr. Sharp remarked that these findings “indicate that this is beginning to become possible.”

Sources: Technology Review, Medscape.com

Researchers Identify Gene That Guards Cancer From Chemo

A cancer gene known as astrocyte elevated gene-1 (AEG-1) has been identified as a major contributor to chemotherapy resistance, according to researchers at Virginia Commonwealth University. The findings suggest that future treatment methods focused on switching off the expression of this gene may improve treatment success of chemotherapy regimens.

Cancer researchers have long viewed AEG-1 as an important gene in the study of cancer. Previous studies have already shown that the gene facilitates cancer cell survival by regulating a variety of critical intracellular processes. Now, the VCU team reports that AEG-1 is also responsible for regulating a tumor’s level of protective autophagy – a process that bolsters the cancer’s defenses against drugs and environmental attack.

According to Paul B. Fisher, Ph.D., of VCU Massey Cancer Center, “Understanding how AEG-1 promotes resistance to chemotherapy and enhances cancer cell survival may lead to treatments that inhibit this gene and its regulated pathways, thereby uncovering potentially new therapeutic targets that can be exploited to enhance the ability of anticancer drugs to fight tumors.”

The findings, which were published in the November 22nd online early edition of the Proceedings of the National Academy of Sciences (PNAS), may one day improve the survival rates of patients for a variety of aggressive cancer types.

Source: http://www.dddmag.com/news-Gene-Protects-Cancer-from-Chemo-112310.aspx

Skin Rash From Erbitux Linked to Improved Lung Cancer Survival

Lung cancer patients who developed a rash following treatment with cetuximab (Erbitux) lived longer than those who displayed no such side effects, according to researchers at Hospital Grosshandsdorf in Germany.

While drug side effects are generally seen as a negative outcome of treatment, it would appear that individuals taking Erbitux might come to view skin rash as a positive sign.

For the study, the German researchers looked at hundreds of patients who had been diagnosed with non-small-cell lung cancer. Of the 518 patients reviewed who had taken Erbitux, it was noted that approximately 70 percent eventually reported an acne-like rash on the skin. This rash typically showed up within the first three weeks of treatment.

Surprisingly, the researchers noted that this sector of patients went on to live much longer than the non-rash sector. On average, those who reported a rash survived for 15 months, while those without a rash survived an average of 8.8 months.

Additionally, patients with the rash displayed an increased stoppage of cancer progression (5.4 months compared to 4.3 months).

While it is currently unclear why a skin rash may be an indicator to success rate for Erbitux, the findings could help doctors assess the effectiveness of lung cancer treatments in the future. Presumably, the manifestation of skin rash would indicate that Erbitux is delivering a positive effect on an individual’s cancer. As such, absence of the rash may help identify patients who need to be switched to an alternative treatment method.

Before such avenues can be recommended, the German team stresses that additional studies must be conducted to validate these initial findings. According to Dr. Francesco Perrone of the Istituto Nazionale Tumori in Naples, Italy, “The only way to verify the hypothesis that skin rash predicts the benefit of cetuximab is a randomized trial that compares interruption versus continuation of cetuximab in patients with skin rash after three weeks of treatment with cetuximab and chemotherapy.”

Erbitux is currently approved for treatment of squamous cell carcinoma, colorectal cancer and head and neck cancer. The drug is currently in Phase III clinical trials for the treatment of non-small cell lung cancer.

Sources:
http://www.emaxhealth.com/
http://www.businessweek.com/

Improving Treatment by Targeting Cancer Stem Cells

Studies completed in 2008 suggested for the first time that cancer tumors might contain cancer stem cells. Stem cells are basic cell structures that have the ability to grow into a diverse variety of cell types. As such, cancer stem cells are the initial cancer cells that grow and divide to proliferate the illness.

Today, a wide variety of cancer drugs and treatments are effective at killing a high number of cancer cells. However, the ability of cancer stem cells to survive these treatments and start the growth process all over again often prevents them from offering long-term health benefits.

With the discovery of cancer stem cells, interest has quickly grown in favor of the idea for developing drugs that specifically target these unique cell structures.

Robert A. Weinberg of MIT and the Whitehead Institute for Biomedical Research is one of the emerging experts on the subject (it was his 2008 research that led to the discovery of tumor cells that may indeed harbor stem cells). Weinberg has worked closely with Piyush Gupta, a researcher that has done extensive research into how current drug treatments affect cancer stem cells.

As it turns out, there are currently very few conventional cancer drugs that measurably affect the health and function of cancer stem cells. With this fact in mind, Gupta set to work screening 16,000 unique compounds in the hopes of finding specific drugs that might effectively target stem cells.

Through Gupta’s research, it was found that an antibacterial known as Salinomycin proved to attack a large proportion of breast cancer stem cells. Now, a startup known as Verastem intends to research how Salinomycin may be used to create the first cancer treatment that specifically targets cancer stem cells.

Verastem also plans to screen an additional 300,000 compounds in an effort to find additional options that may target cancer stem cells.

Another startup that is focusing on cancer stem cell research is OncoMed. Based in Redwood City, CA, OncoMed researchers are looking to find ways to reduce the ability of cancer stem cells to self-renew. OncoMed currently has entered stage 1 clinical trials with its inaugural drug (OMP-21M18).

Source:
http://www.boston.com/