Mesothelioma is an aggressive cancer caused by asbestos exposure. The disease has a very long latency period and is often not discovered until decades later, after the disease has progressed to an advanced stage leaving patients with limited treatment options.  Chemotherapy is considered the most effective single modality for the treatment of mesothelioma. However, mesothelioma has shown to be chemo-resistant and the chemotherapy is primarily used to relieve symptoms.  

Ravi K. Amaravadi, MD, an assistant professor of Medicine at the Perelman School of Medicine and Abramson Cancer Center at the University of Pennsylvania, found that combining hydroxychloroquine (HCQ), a drug currently used in the treatment of malaria and rheumatoid arthritis, with cancer therapies, such as chemotherapy, “can enhance the antitumor activity of these drugs in laboratory models of treatment-resistant cancers.” 

Amaravadi and his team believe HCQ blocks autophagy, the process of “self-eating” within cells, and stops the continued growth of cancerous cells.  The researchers reported that autophagy is increased in cancer cells, and the cells might actually “be addicted to autophagy.” Autophagy, Amaravadi believes, is the way cancer cells evade chemotherapy. 

“While our knowledge of the role of autophagy in cancer is still in its infancy, the opportunity to learn about autophagy, both at the bench and the bedside, could accelerate the translation of basic advances in this field into clinical benefit for patients with cancer,” says Amaravadi.

According to the report, over 30 clinical trials have been initiated for HCQ to test the effectiveness of the drug with various cancers.  One clinical trial is underway to determine if adding HCQ to erlotinib helps in the treatment of non-small cell lung cancer.  Erlotinib is a tyrosine kinase inhibitor which is shown to block a protein called the epidermal growth factor receptor which is found in lung cancers. 

In a separate study, researchers at Johns Hopkins found that compared with lapatinib, erlotinib appeared to prevent altered EGFR from working.  They concluded “erlotinib is a better drug treatment for non-small cell lung cancers that are associated with altered forms of EGFR protein.” 

Nearly 3,000 Americans are diagnosed with mesothelioma each year. Many of them rely on clinical trials for the opportunity to receive new, potentially curative therapies. 

The Penn findings were reported at the annual American Association for Advancement of Science meeting being held this week in Vancouver, British Columbia.

Mesothelioma is a rare, aggressive form of cancer primarily caused by exposure to airborne asbestos fibers.  Each year close to 3,000 Americans are diagnosed with the incurable cancer. While there is currently no known cure for the disease, many clinical trials and studies are underway that could offer hope to mesothelioma patients through discovery of new approaches to treat the disease, to develop procedures to detect the disease at an early stage and to find a cure.   

“This year we have awarded another half million dollars toward the search for a cure. Our mission to cure meso is clear and we won’t stop until it’s accomplished,” said Kathy Wiedemer, the executive director of the Meso Foundation.

This year’s funded mesothelioma projects are:

• Tao Dao, MD, PhD, Memorial Sloan Kettering Cancer Center – TCR-like mAb specific for WT1 peptide/MHC complexes on mesothelioma
• Assunta DeRienzo, Brigham and Women’s Hospital – Identification of Novel Mutations in Malignant Pleural Mesothelioma using Deep Whole-Genome Sequencing
• Marc Ladanyi, Memorial Sloan-Kettering Cancer Center – Frequent inactivation of BAP1 in mesothelioma: biology and new therapeutic opportunities
• Liang-Chuan S Wang, Perelman School of Medicine at the University of Pennsylvania – The Role of the IFN response in Chemosensitivity of Mesothelioma to Pemetrexed
• Nadia Zaffaroni, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy – Identification and validation of miRNAs as novel biomarkers and therapeutic targets in diffuse malignant peritoneal mesothelioma 

The five new grants will bring to 76 the total number of grants funded by the Meso Foundation.  The grants were selected from among 46 applications.  The Mesothelioma Applied Research Foundation instituted its grant funding program in 2000 and has since awarded over $7.6 million to critical research, stimulating the field of mesothelioma research and encouraging scientists to devote their life-work to this under-researched cancer.

Mesothelioma often has a complex growth pattern ruling out surgery and radiation therapy since pinpointing the malignant cells is difficult.  As a result, chemotherapy is the primary treatment modality.  Although lung cancer is characterized by more distinct, individual tumors, oncologists rely on chemotherapy for lung cancer as well.  Platinum-based drugs, including cisplatin, paclitaxel, carboplatin and doxorubicin, are frequently used to treat both lung cancer and mesothelioma.

In a study published in Nature Structural & Molecular Biology, Johns Hopkins researchers reported that “DNA changes in a gene that drives the growth of a form of lung cancer can make the cancer’s cells resistant to cancer drugs.”

This proved that some classes of lung cancer drugs will not work and that kinase inhibitors may be more effective. Kinase inhibitors have long been thought to be the key to developing drugs that kill mesothelioma cancer cells, however, the results have not been conclusive. Kinases are responsible for transforming healthy cells into cancerous cells.

Further, the authors found that “different forms of EGFR [epidermal growth factor receptor] protein reacted in unexpected ways,” and by better understanding these factors they could better predict the effective treatments.   They found that not all EGFR proteins variations responded to the same drugs that normal EGFR protein did. 

EGFR is a protein found on the surface of some cells to which epidermal growth factor binds, which causes the cells to divide and spread. It is found at abnormally high levels on the surface of many types of cancer cells.  

The Hopkins team found that compared with lapatinib, erlotinib appeared to prevent altered EGFR from working.  As a result, they concluded “erlotinib is a better drug treatment for non-small cell lung cancers that are associated with altered forms of EGFR protein.”  Erlotinib is an oral pill used to treat non-small cell lung cancer that has metastasized in patients who have already been treated with at least one other chemotherapy medication and have not improved.

These findings support the recommendations made last year by the American Society of Clinical Oncology that physicians should determine the EGFR mutations in cancer patients when determining the appropriate treatment.

Researchers at Johns Hopkins participated in a study last year where they found that targeting and blocking the Hedgehog signaling pathway, which is responsible for signaling cancer cells to grow, could “increase the effectiveness of chemotherapy and reduce the risk of cancer relapse.”

Lung cancer is the second leading cause of death in the United States and afflicted 157,300 Americans in 2010, according to federal statistics.  Close to 3,000 people in the U.S. are diagnosed with mesothelioma each year. Currently, mesothelioma is considered incurable and, the prognosis is often less than one year.

In a previous article, we reported that there are currently no effective, non-invasive methods for early detection or treatment monitoring for either lung cancer or mesothelioma.

Mesothelioma is a serious cancer most often affecting the lining of the lungs that occurs in individuals exposed to airborne asbestos fibers.  Asbestos is a known carcinogen and is also proven to cause asbestosis and lung cancer.  While pleural mesothelioma is not classified as a lung cancer according to the medical definition, the diagnosis and treatment of lung cancer and pleural mesothelioma are often similar.

Backman, professor of biomedical engineering at Northwestern University’s McCormick School of Engineering and Applied Science, and Hemant K. Roy, M.D., of NorthShore University HealthSystem, have been focusing on the use of biophotonic technology to develop a process to make early cancer detection “cheaper, more accurate and less invasive for an array of cancers.”  Biophotonics is a combination of biology and photonics, in which the researchers are able to take harvested cells and shine a light on them to determine whether lung cancer is present.  

The photons bounce off the molecular structures at different angles depending on whether the cells are healthy or not.  According to the researchers, the process is highly sensitive and can detect subtle abnormalities elsewhere in the body. Backman said they are able to see alterations in cells that are indicative of pre-cancer that could not be seen under a microscope. 

In a clinical trial at Evanston Hospital of nearly 100 lung and colon cancer patients, the results proved to be 90 percent accurate.  Roy said of the technology, “I think if this works, we could really make a big difference in how we treat patients.” 

The use of shining lights on cancer cells for detection is not new and is being researched in various other studies.  Cornell is researching “glowing dots” that would attach to cancer cells and glow during a PET scan.  In Austria, researchers are testing the use of fluorescence spectroscopy where a laser probe is shined on human tissue and the cells become “excited” by the light and emit a unique color indicating cancer. 

Lung cancer is the second leading cause of death in the United States and afflicted 157,300 Americans in 2010, according to federal statistics.  3,000 Americans die from mesothelioma each year.  Early detection of mesothelioma can positively influence a patient’s survival by increasing treatment options and improving their quality of life while battling the cancer.

According to a news article from McGill University, metformin “reduces the cellular mutation rate and the accumulation of DNA damage.”  The researchers report that while it is widely known that such mutations are directly involved in causing cancer, no other researchers have shown that the risk of developing cancer can be reduced by inhibiting the mutation rate. 

Pleural mesothelioma, a cancer of the lining of the lungs, is caused by breathing in asbestos dust.  The microscopic fibers penetrate the lungs and damages the healthy mesothelial cells.  In effect, asbestos damages DNA, the material within a cell that provides each person’s genetic blueprint, causing faults in genes that then leads to cancer.  If the DNA damage can be prevented, mesothelioma may not form. 

During the study, the researchers found that metformin, a drug used in the treatment of Type 2 diabetes, reduces DNA damage by reducing levels of reactive oxygen species (ROS). ROS are known to be DNA-damaging agents produced as by-products when cells generate energy from nutrients, according to the article. 

Dr. Michael Pollak, professor in McGill’s Departments of Medicine and Oncology, researcher at the Lady Davis Institute for Medical Research at the Jewish General Hospital and the study’s director,  said, “This study opens an exciting new direction in cancer-prevention research.”  He added while further studies are needed, “the possibility of protecting DNA from oxidative damage by the use of a well-tolerated drug was not expected.” 

Close to 3,000 Americans are diagnosed with mesothelioma yearly.  Although there is no cure for mesothelioma, it can be treated with varying degrees of success through the use of surgical procedures, chemotherapy and radiation. 

The full article was published in the journal Cancer Prevention Research.

Mesothelioma, which claims 2,000 to 3,000 American lives each year, is a usually-fatal lung cancer caused by inhaling tiny asbestos fibers. Because asbestos breaks down easily, a single exposure to asbestos can result in the disease. Mesothelioma may take several decades to manifest. 

The prior heavy use of asbestos left trade workers such as insulators, plumbers and pipefitters, electricians, sheet metal workers, auto mechanics, refinery and factory workers, construction workers and shipyard workers, and their families who breathed asbestos dust decades ago vulnerable to contracting asbestos-related diseases including asbestosis, mesothelioma and lung cancer. 

Although the use of asbestos has been curbed in the United States since the late 1970s, researchers at the University of Hawaii (UH) Cancer Center recently reported that the incidence of mesothelioma has been increasing in the United States and will continue to do so.   In fact, the researchers estimate that more than 20 million people in the United States are at risk of developing malignant mesothelioma due to asbestos exposure.

The American Cancer Society report attributes the decline in cancer cases to advances in cancer screening and treatment.  However, as previously reported, the existing cancer screening tools are inadequate and ineffective as screening tests for mesothelioma.  Although scientists have been working hard to develop one, typically diagnosis is not made until symptoms are advanced and the patient is suffering from life-threatening complications. 

The American Cancer Society estimates a total of 1,638,910 new cancer cases and 577,190 deaths from cancer in the United States in 2012.

NMVB is provided through a collaborative effort of the Departments of Biomedical Informatics, Epidemiology, and Pathology at the University of Pittsburgh, and funded by a grant from the National Institute of Occupational Health and Safety of the Centers for Disease Control and Prevention (CDC).  CDC provided $5 million of funding in 2010 to keep the bank operating for another five years. 

This virtual bank links data associated with specimens collected and stored at different institutions across the United States. The NMVB provides real-time access to all information for the mesothelioma tissue sample including demographic, epidemiologic, pathologic, genotype, and follow-up data associated with biospecimens. 

NMVB has over 1,000 biospecimens including: paraffin embedded tissue, fresh frozen tissue, and developed mesothelioma tissue microarrays (TMAs) with associated multimodal data annotation. 

While the database and specimens were intended for research studies for mesothelioma, the NMVB Steering Committee noted in their November 7, 2011, meeting minutes that legal experts have been requesting specimens in support of mesothelioma lawsuits.  During a mesothelioma lawsuit, medical experts are often requested to assist with the interpretation of medical information.

The Steering Committee agreed that the use of these specimens and the data during a legal action is beneficial, but they expressed concerns that this limits the number of specimens available to active researchers.  Ideally, lawyers will return the specimen at the end of the lawsuit; however, the committee is concerned with quality assurance of the returned samples.

Biospecimen and associated data sets are applied for and evaluated by the Research Evaluation Panel (REP), an independent scientific review group, before releasing the information.

Mesothelioma is a rare, serious cancer most often affecting the lining of the lungs that occurs in individuals exposed to airborne asbestos fibers.  While pleural mesothelioma is not classified as a lung cancer according to the medical definition, the treatments for lung cancer and pleural mesothelioma are often similar. Currently, there is no effective screening method for determining the appropriate treatment for a mesothelioma patient. 

Circulating cancer cells detected through the test can indicate that a tumor has spread or is likely to spread.  The use of the “high-throughput matrix-assisted laser desorption/ionization time-of-flight mass spectrometry single nucleotide polymorphism analysis (MALDI-TOF MS SNP)” allows the researchers to identify the genetic mutations, or biomarkers, from the few malignant cells that can be applied to CTC samples. 

The biomarkers in turn are used to track progress of “genetic changes and thus monitor the cancer and the effectiveness of any treatments being administered.”  The test can also be effective for developing new drugs and possibly, a cure for mesothelioma.  Mesothelioma is considered incurable. 

“We have developed an extremely sensitive test that could be able to detect mutations present in circulating tumor cells (CTCs), and we are hoping that from their characterization, we would be able to understand diagnostic, prognostic and predictive markers,” said Heidi S. Erickson, Ph.D., assistant professor of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center. 

The MALDI-TOF-MS SNP test is still being tested in the lab.  The next step is to identify samples from actual lung cancer patients. 

MD Anderson treats approximately 150 mesothelioma patients each year, with the number continuing to grow.   The mesothelioma cancer program has over 30 experts representing the areas of thoracic surgery, thoracic medical oncology, radiation, pulmonary, and pathology – all with an expertise dedicated and focused on mesothelioma.  

Just this year, Anne Tsao, M.D., associate professor in MD Anderson’s Department of Thoracic/Head and Neck Medical Oncology and director of its Mesothelioma Program, declared one of her mesothelioma patients cancer free. 

Erickson presented the findings at the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer: Biology, Therapy and Personalized Medicine, held Jan. 8-11, 2012.

Malignant mesothelioma is a rare, fatal form of cancer caused specifically by exposure to asbestos. Most cases of mesothelioma are diagnosed 30 years or more after exposure.  Early detection improves survival chances, but most often diagnoses are not made until symptoms appear and the disease has progressed to an advanced stage leaving the patient with life-threatening complications.

India, which uses asbestos extensively in products and construction, has not historically tracked mesothelioma cases. India is known to have poor worker safety laws and continues to contribute to the growing global mesothelioma burden by failing to admit to the mesothelioma-causing properties of the mineral, according to a study published early this year in Environmental Health Perspectives.

Azad said that the government has launched a pilot project across 100 districts in 21 states for “prevention and control of cancer, cardio-vascular diseases, stroke, and diabetes.”  He adds, “India will be the first country in the world to screen the entire population in the next five years.”  Although details of how and where the screenings will be conducted were not released, Azad said the equipment and the chemotherapy will be provided by the union health ministry.

Major Gen (Retd) M. Srivastava, VSM, National Accreditation Board for Hospitals & Healthcare Providers assessor, commented that while this is a “good initiative,” it requires “comprehensive operational and logistical planning.”

Screening tests for mesothelioma may include:

• Physical examination by a doctor,
• Routine blood test,
• Breathing test,
• Interview by doctor or nurse about medical history,
• Questionnaire about occupational exposure.

According to India’s Ministry of Health and Family Welfare, 2.7 million Indian’s have cancer and close to 1.1 million new cases are diagnosed each year.  It is unclear how many residents are diagnosed with mesothelioma.

Mesothelioma, a rare form of asbestos-related cancer, typically affecting the lining of the lungs, is highly aggressive and is resistant to many cancer treatments making it a difficult disease to treat effectively.  The prognosis for mesothelioma patients is usually grim: the average survival time varies from 4 – 18 months after diagnosis.

According to Professor Julian Peto, of the London School of Hygiene and Tropical Medicine and the Institute of Cancer Research, the UK now has the highest death rate in the world from mesothelioma, with over 2,000 deaths a year.   The disease is currently not curable and typical treatments include surgery, chemotherapy and radiation. Mesothelioma causes an estimated 15,000 to 20,000 deaths per year worldwide.

Realizing that, as with mesothelioma, the most effective cancer treatments are based on the patient’s genetic make-up, Cancer Research UK has established the Stratified Medicine Programme with a goal to develop a national service to offer “standardized, high quality, cost-effective genetic testing of tumors.”   

Patient-centric treatment involves using genetic testing to identify one or more specific biomarkers that can allow a doctor to determine, for example, whether a person is responding to a medicine and whether another drug may be more effective.  Personalized medicine allows physicians to use indentifying characteristics of a patient’s tumor to drive treatment.

Just this year, Pfizer presented data from the preliminary results of a clinical trial for their oral anti-cancer drug crizotinib.  Used in the treatment of non-small cell lung cancer, the pill appears to double survival over standard drugs against tumors with the anaplastic lymphoma kinase (ALK) genetic marker.  There is a potential that the marker is also present in certain pleural mesothelioma cases making it a new treatment option for the disease.

Development of the Programme will be a multi-phased, multi-year project.   Implementation of the project will also include creation of a national database of “tumor genetic information, treatments and outcomes that will help researchers design more effective cancer treatments in the future.”