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Preclinical evaluation of MORAb-009, a chimeric antibody targeting tumor-associated mesothelin

Friday, February 29, 2008

Source: CancerImmunity.org

People often speak mistakenly of cancer as if it were a single disease that just happens to target different areas of the body. In fact, cancer is not a single disease, but a family of diseases whose propagation is driven by a breakdown of the same cellular processes that are normally responsible for keeping people healthy. When these processes are undermined by aberrant cellular activity, the strict regulation of cell division and growth is compromised and the malignant cells that do develop are ones that put the health of the entire body into question. This is the reason why no single cure for cancer exists—and probably never will exist—and why cancer research requires both great scientific understanding and great creativity.

The key to treating individual forms of cancer is to understand the particular molecular and biological features involved in the genesis of these specific tumor types and to then develop targeted agents that attack the structures upon which tumors can grow. In the quest for a cure for mesothelioma, scientists have discovered a number of proteins that are overexpressed in malignant tissue and they hope a better understanding of the structures which produce these proteins will lead to better treatments for mesotheloima patients.

One such protein that has received a great amount of attention is mesothelin, which is a membrane-bound glycoprotein that has been implicated not only in all forms of mesothelioma, especially pleural mesothelioma and peritoneal mesothelioma, but in pancreatic and ovarian cancer, as well as in lung adenocarcinoma. Now considered a therapeutic target for treatment, mesothelin is the subject of a number of research programs, one of which we will now be covering. An international team of researchers has recently released the results of a pre-clinical study of a monoclonal antibody they developed, MORAb-009, that targets tumor-associated mesothelin.

Introduction to the Study

Monoclonal antibody therapy is a treatment method where antibodies specific to a particular substance or cell-type are created that will then bind to this substance or cell-type and stimulate the immune system to attack the entire cell-antibody domain. In the case of cancer research, monoclonal antibodies are created for specific tumors or the receptors which stimulate tumor growth and then the tumor-antibody domain is attacked and, ideally, removed from the system.

As we noted above, mesothelin has been identified as significantly over-expressed in all pancreatic adenocarcinomas and in all mesotheliomas, as well as ovarian cancers and lung adenocarcinoma and non-small cell lung cancer. Its expression in normal tissues is limited to the mesothelial cells in the pleura, pericardium and peritoneum, so targeting agents that can bind with tumor-related mesothelin are potentially beneficial for a number of different cancers.

The researchers developed a monoclonal antibody called MORAb-009 to bind to mesothelin-expressing tumor surfaces, but not to other membrane-bound proteins that have been implicated in tumor genesis. Using immunohistochemical analysis, the authors were able to show that MORAb-009 was able to bind to tumor-associated mesothelin and then become internalized into the cell surface. They were also able to show that MORAb-009 could disrupt cell adhesion between mesothelin and its ligand (i.e., a smaller molecule that binds to a larger one, such as a receptor protein) CA125/MUC16—a combination thought to facilitate metastasis to the peritoneum.

Another phase of their research had the authors studying its toxicity and its anti-tumor effects. In toxicity tests on cynomolgus monkeys, MORAb-009 was well-tolerated and exhibited a favorable toxicity profile. While on its own MORAb-009 only showed moderate anti-tumor activity, when researchers combined it with the chemotherapy agents Taxol® and gemcitabine, they found significantly enhanced activity. Although the precise mechanism of this multiplicative effect is presently unknown, the authors still hypothesize that due to its low toxicity and its overall efficacy, the MORAb-009-chemotherapy axis is potentially quite useful for the treatment of cancers expressive of mesothelin.

Conclusion

In light of their successful pre-clinical studies, the authors have commenced a Phase I clinical study with patients who present with one of the aforementioned cancers: pancreatic and ovarian cancers, lung adenocarcinomas and all forms of mesothelioma. However, as the pre-clinical phase was made up of entirely non-human subjects, this Phase I trial is simply the first of much more research that needs to be completed on the feasibility of MORAb-009 therapy in humans before any firm conclusions can be drawn regarding its efficacy.

Labels: mesothelioma

posted by Belluck & Fox at 5:45 PM
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EGFR and PDGFR Differentially Promote Growth In Malignant Epitheloid Mesothelioma Of Short- And Long-term Survivors

Thursday, February 28, 2008

Source: Pubmed.gov

One of the most difficult aspects of a mesothelioma diagnosis for the patient and his or her family is coming to terms with the disease’s median survival figure, which states that the average life expectancy after diagnosis is only between 8 and 14 months long. Less than 10% of patients will survive for three or more years. While more precise surgical techniques and more effective chemotherapy regimens have had a positive effect on life expectancy, the overall successes have been limited and the survival differences compared to previous techniques are ones of degree, not of kind. For reasons still unknown, the great successes that medicine has had in treating other forms of cancer have not been replicated in the treatment of mesothelioma.

Many doctors feel that the key to more effective management of the disease is to better understand its molecular and genetic behavior. To this end, there are a number of research programs being conducted internationally that are attempting to uncover this information. A team of researches from Austria has recently released the results of a study that compared differences in protein expression and the role of signaling pathways between long-term and short-term survivors of pleural mesothelioma. Their results indicate that mesothelioma acts differently with long-term survivors than it does short-term survivors.

Introduction to the Study

To investigate the role played by the different signaling pathways, the researchers identified tissue samples from 70 previous cases of malignant pleura mesothelioma. Of these 70 samples, 48 were identified as epitheloid mesothelioma and included in the study. These samples were selected because the 10% of mesothelioma patients who survive longer than three years exclusively present with epitheloid mesothelioma. There were 26 cases of long-term survivors (LTS) and 22 cases of short-term survivors (STS). The median survival figure of the LTS group was 50.7 months, while the median survival figure of the STS group was only 9.1 months.

The initial samples were taken from tissue surgically-resected through a biopsy or a pleurectomy and then combined into a tissue microarray for immunohistochemical analysis, which revealed significant differences in protein expression between the LTS group and the STS group.

LTS Group

The LTS group showed overexpression of EGFR (epidermal growth factor receptor), which is the receptor for members of the epidermal growth factor family of extracellular protein ligands. EGFR overexpression has been implicated as a causative factor in a number of other cancers. In the LTS group, EGFR overexpression was the primary signaling pathway at work, which led to a specific protein expression profile that was not replicated in the STS group.

Previous research on EGFR signaling in mesothelioma concluded that EGFR blocking therapies were only valuable for a distinct minority of mesothelioma patients and the researchers here hypothesize that it is the same minority of patients who end up as long-term survivors that would be the principal beneficiaries of EGFR blocking.

STS Group

In the STS group, the researchers found that protein expression was more highly correlated with PDGFR (Platelet Derived Growth Factor Receptor) than it was EGFR. While both groups expressed similar levels of EGFR and PDGFR, and in some cases, even activation of the same proteins, in the case of the STS group, actual protein expression was driven by PDGFR signaling, while in the LTS group it was driven by EGFR signaling.

Protein Expression Between LTS and STS

Even though some of the same proteins were expressed in both groups, the overall expression profile was quite different. Both groups did show significant up-regulation of TIE2/Tek—which had not previously been discussed in relation to mesothelioma, but has been implicated with other cancers. In the LTS group, TIE2 up-regulation correlated with EGFR expression, while in the STS group it correlated with PDGFR expression.

The STS group also showed a much higher expression of survivin, which is a protein that inhibits apoptosis. Survivin overexpression has been identified in previous mesothelioma research as a primary reason for the disease’s poor response to chemotherapy and radiation. The researchers hypothesize that survivin up-regulation is induced by STAT1 expression, which was a surprise because previous research had concluded that STAT1 was a tumor suppressor and its siblings STAT3 and STAT5 were the oncogenes (a gene that can transform a healthy cell into a cancerous one). These findings indicate that in pleural mesothelioma STAT1 seems to act like an oncogene. Previous research on STAT1 expression has shown it can provide resistance to cisplatin and to radiation, which are often seen in mesothelioma.

Survivin and STAT1 expression did not play a significant role in the LTS group, although STAT3 was overexpressed in this group.

Conclusion

This paper was the first to compare signaling pathways and protein expression between a short-term group of mesothelioma survivors and a long-term group and the analysis indicates significant differences in signaling systems and protein expression. The hope, as in all cases of mesothelioma treatment research, is that these findings will lead to the development of important new treatment modalities. However, the researchers are quick to note that their paper only offers a number of hypotheses and that much more research needs to be completed before definitive conclusions can be drawn from their research.

Labels: mesothelioma

posted by Belluck & Fox at 6:20 PM
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NCGR Software Enables Identification of Mutated Genes Unique to Mesothelioma Tumors

Tuesday, February 26, 2008

Source: Fox Business.com

The National Center for Genome Resources has announced the launch of Alpheus, the first web-based software system designed for the analysis of massive DNA sequencing projects. The system will enable researchers to analyze extremely large DNA data sets to find individual, patient-specific gene mutations.

Doctors from the International Mesothelioma Program at Brigham and Women’s Hospital in Boston used Alpheus to sequence all of the genes expressed in tumor tissue from four patients with mesothelioma. Approximately 266 million bases were sequenced per patient. The resulting analysis identified 15 novel gene mutations, none of which had previously been implicated in the development of mesothelioma. Alpheus also revealed each tumor’s unique mutation profile.

Dr David Sugarbaker, Chief of the Division of Thoracic Surgery at Brigham and Women’s Hospital and an internationally-regarded expert on mesothelioma, said “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.”

Dr. Sugarbaker’s remarks express the great promise this new tool has in the treatment of all forms of cancer: by understanding the mutation profile of individual tumors and the expression of particular genes in a given patient, the door is opened to the possibility of truly targeted cancer therapies.

To learn more about Alpheus, please visit the Alpheus pages on the NCGR’s website.

Labels: mesothelioma

posted by Belluck & Fox at 2:32 PM
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Pre-Clinical Data Show Intracellular Pathways Affected by ONCONASE(R)

Monday, February 25, 2008

Source: Alfacell Corporation

Alfacell Corporation has recently announced the identification of the genes and signaling pathways impacted by ONCONASE®, it’s anti-cancer drug that triggers apoptosis in malignant cells while leaving healthy cells alone. ONCONASE has shown great promise for the treatment of mesothelioma, as well as a number of other cancers.

Alfacell presented this latest data at the 5th Cancer Drug Research & Development conference. Its presentation identified 181 individual genes that were up- or down-regulated by ONCONASE, and these genes triggered apoptosis in specifically malignant cells. Alfacell also identified the intracellular MAPK signaling pathway as impacted by ONCONASE.

Susanna Rybak, Ph.D., a member of Alfacell’s scientific advisory board, described their findings as, “This work may explain the intrinsic anti-tumor activity seen after ONCONASE treatment through the identification of the specific genes affected and the biological pathways impacted…Additionally, this data is helping us to better understand the optimal intracellular pathways for developing antibody targeted ONCONASE compounds.”

It is hoped that further understanding the actual genes and pathways involved in ONCONASE therapy will allow Alfacell to engineer more targeted and effective compounds. ONCONASE is currently being studied in a Phase III clinical trial for people with unresectable pleural mesothelioma.

Labels: mesothelioma

posted by Belluck & Fox at 9:16 AM
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Las Vegas Doctor’s Cancer Drug Accepted for Human Testing

Friday, February 22, 2008

Source: Las Vegas Sun

The Las Vegas Sun is running an article on the pioneering cancer research of Dr. Nam Hoang Dang, chief of hematological malignancies at the Nevada Cancer Institute. Dr. Dang has developed a compound that he believes can cure certain forms of cancer, including kidney cancer, mesothelioma and T-cell lymphoma. The FDA has recently given its approval to Dr. Dang to start a Phase I clinical trial of the drug, which he began work on twenty-four years ago.

When Dr. Dang was studying for his M.D. and Ph.D. degrees at Harvard University, he discovered a molecule, known as CD26, that plays an essential role in the formation of multiple types of cancer. He then began work on developing a CD26 antibody to attack those cancer cells. He claims that lab- and animal- studies have confirmed the anti-cancer benefit to his drug and now the FDA has given its approval to start the first round of human trials. Dr. Dang believes that targeted therapies, like his drug and ones similar to it, represent a real advance in cancer treatment over traditional options, such as chemotherapy, because they target specific weak points in a cancer cell and then exploit those weak points to stop the growth of the cancer.

It takes many years for a drug to reach the market, so even if the phase I tests are successful for Dr. Dang, it will be quite sometime before actual patients are given his compound. However, his work still represents a major breakthrough in our understanding of the physiological aspects of carcinogenesis and all involved are hopeful that his research will lead to real improvements in the lives of mesothelioma patients, as well as other cancer patients, all over the world.

Labels: cancer, mesothelioma

posted by Belluck & Fox at 2:07 PM
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Symptoms and Patient-Reported Well-Being: Do They Predict Survival in Malignant Pleural Mesothelioma?

Thursday, February 21, 2008

Source: Journal of Clinical Oncology, Vol 25, No 36 (December 20), 2007: pp. 5770-5776

Research into the discovery of independently-useful prognostic factors for patients with mesothelioma makes up a growing number of trials and studies. Because this disease has proven so difficult to treat, the discovery of additional factors or improvements upon current factors may give doctors one more tool in the fight for their patients’ lives. A number of models have been proposed for this purpose, but few have taken into consideration patient-reported symptoms as independent prognostic factors. A recent article in the December 20, 2007 edition of the Journal of Clinical Oncology reports on such a study. The article describes the use of specific patient-reported symptoms in the development of prognostic factors for patients with pleural mesothelioma.

Introduction to the Study

The fundamental question the study inquired into was the relationship between overall survival and individual prognostic factors, using a recently-proposed medical prognostic model and one developed by the analysis of patient-reported symptoms. For the former, the authors utilized the European Organization for Research and Treatment of Cancer (EORTC) prognostic index (PI), which is an index developed from an analysis of “histologic subtype, interval since diagnosis, platelet count, hemoglobin and disease stage.” Along with the EORTC PI, they collected data from patients regarding symptoms using two standards for self-reported symptoms of health-related quality of life (HRQOL), EORTC QLQ-30 and the QLQ-LC13. The former standard, QLQ-30, measured functional living abilities, symptom groups and individual symptoms. The latter, QLQ-LC13, was setup to measure individual reactions of lung cancer patients to symptoms, treatment effects and pain medication. Information from both standards included patient descriptions of functional scales, including physical, role, emotional, cognitive and social abilities, as well as reports of a number of individual elements, such as pain, loss of appetite, nausea, cough, dyspnea, as well other factors.

The authors enrolled 250 patients with pleural mesothelioma into their randomized study. 126 patients received ralitrexed and cisplatin, while 124 received cisplatin alone. To be eligible for the study, patients must have presented with non-resectable, histologically-proven pleural mesothelioma, demonstrated a WHO performance score between 0 and 2 and showed healthy function of liver and kidneys. Median survival for both groups was 10.1 months, with no statistically significant differences between cohorts.

Of the 250 patients enrolled, 229 met the baseline standard for HRQOL descriptions, so those 229 were the sample populatoin used in the analysis of patient-reported symptoms.

Conclusion

At first glance, many of the HRQOL descriptions appeared significant, but when looked into further, few could be independently correlated as a prognostic factor. Using a number of statistical techniques, the authors finally concluded that the elements most effective as prognostic factors for patients with mesothelioma were the EORTC PI and patient-reported symptoms of pain and appetite loss. Physical functioning was also implicated as a prognostic factor, but was more significant when correlated with pain and appetite loss, so they were seen as the significant, independent factors.

These findings do represent an important contribution to the diagnosis and treatment of mesothelioma, as they point towards the beginnings of a prognostic model for this difficult disease.

Labels: mesothelioma

posted by Belluck & Fox at 4:19 PM
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Malignant Pleural Mesothelioma: Surgical Management in 285 Patients

Wednesday, February 20, 2008

Source: The Annals of Thoracic Surgery

The search for a cure for mesothelioma is a regular battle in hospitals and research facilities all over the world. The traditional modalities of cancer treatment—surgery, chemotherapy and radiation—have not yet succeeded in stopping this terrible illness, but pioneering physicians are exploring new techniques, as well as refining traditional treatments. An important element in the process of refining standard therapies are the papers summarizing the historical efficacy of individual surgical methods. These analyses give doctors statistical information on a specific institution’s experience with these techniques, which can be helpful in determining treatment courses for future patients who may be eligible for similar surgeries. Doctors from the Mayo Clinic have recently released a paper that summarized the Clinic’s previous 18 years of surgical experience in the treatment of pleural mesothelioma.

Introduction to the Study

The authors of the paper undertook a retrospective analysis of the Mayo Clinic’s 18 previous years of mesothelioma treatment. Using the Clinic’s main database, they surveyed the results of all patients who underwent surgery for mesothelioma between January 1, 1985 and December 31, 2003.

The surgical procedures identified fell into one of five categories:

1. Extrapleural Pneumonectomy (EPP). The paper defined the extrapleural pneumonectomy as “…the en bloc resection of the involved ipsilateral parietal pleura, lung, pericardium, and diaphragm. The diaphragm and right pericardium were reconstructed with polytetrafluoroethylene soft-tissue patch.”
2. Total Pleurectomy. The paper described a total pleurectomy as consisting “…of a complete extrapleural stripping of the parietal and mediastinal pleura and involved visceral pleura from the ipsilateral hemithorax without performing pulmonary resection. Total pleurectomy also included resection of the diaphragm and pericardium when necessary.”
3. Subtotal Pleurectomy. The authors defined this procedure as “…removal of up to 70% of the parietal pleura with debulking of as much of the mesothelioma as possible. Subtotal pleurectomy was a less extensive resection than total pleurectomy.”
4. Exploration without Resection. The paper describes this procedure as consisting of “…posterolateral thoracotomy with an extensive dissection performed; however, resection of mesothelioma was not ultimately performed because of identification of unresectable disease.”
5. Biopsy Alone. In this case, the authors defined this procedure as “…performed by means of video-assisted thoracic surgery or limited thoracotomy. Biopsy alone involved very limited dissection and resulted in only a pleural biopsy.”

Results

The analysis consisted of 285 patients, of which 236 were men and 49 were women. The average patient age was 66 years old. 146 patients underwent a biopsy alone, 73 underwent an extrapleural pneumonectomy, 34 underwent a subtotal pleurectomy, 22 were given an exploration without resection and 10 patients received a total pleurectomy. Histologically, the patient breakdown was within the expected averages: 134 patients (47%) presented with epithelial mesothelioma, 39 patients (14%) presented with biphasic mesothelioma and 39 other patients presented with sarcomatous mesothelioma, while 18% were unclassified or presented with desmoplastic mesothelioma. In terms of staging, 20 patients presented as stage IA, 82 patients as stage IB, 24 patients as stage II, 75 patients as stage III, 60 patients as stage IV and in 24 patient records a staging classification was not given.

Surgical Breakdown: Extrapleural Pneumonectomy

An extrapleural pneumonectomy is a radical procedure that historically was associated with high mortality and high morbidity. However, it has always had the potential to remove a large extent of malignant tissue, so has often been the treatment of choice for many thoracic surgeons. Improvements in technique have significantly lessened the overall mortality figures, but it is still associated with major complications. In the cohort under discussion, an EPP was the most often used invasive surgical method. Median survival was 16.0 months for this group. One-year survival was listed at 61% and two-year survival at 25%. Slightly greater than 50% of this group experienced a major complication.

Surgical Breakdown: Total Pleurectomy

In most institutions, the two major surgeries performed for mesothelioma are an EPP and a total pleurectomy and there is still disagreement among surgeons regarding which procedure is the most effective. In the case of the Mayo Clinic, only 10 total pleurectomies were performed, so statistical comparisons in this data set are limited by the small sample size. That said, for those patients who received a total pleurectomy at the Mayo Clinic, median survival was 17.2 months, the one-year survival figure was listed at 80% and the two-year figure was listed at 35%, all of which were greater than the EPP group. Only 20% of this group (however, this was only 2 patients) experienced major complications, as compared to 50.7% for the EPP group. Again, though, the small sample size makes precise comparisons between procedures impossible.

Surgical Breakdown: Biopsy Alone

146 patients only underwent a biopsy. This was most commonly done for patients with very extensive disease or for patients with a very low performance status. All surgeries performed for mesothelioma are quite taxing on the body, so patients who present with the above description would only be treated in a palliative manner. The median survival was 9.2 months for this patient class. The one-year survival figure was listed at 36% and the two-year figure at 13%.

Surgical Breakdown: Exploration without Resection and Subtotal Pleurectomy

Neither of these procedures are official treatments. In all cases, the surgeon had planned for an EPP or a total pleurectomy, but interoperation discoveries prevented the full completion of either procedure so the surgeon’s work was limited by the patient’s presentation. The median survival figure for patients who underwent a subtotal pleurectomy was 8.1 months, with the one-year survival figure listed at 30% and the two-year figure at 15%. For patients who underwent an exploration without resection, the median survival time was 6.8 months, with a one-year survival figure of 45% and a two-year figure of 10%.

Conclusion

The results as presented by the Mayo Clinic are within the standard figures for most treatments of pleural mesothelioma. While individual procedures may be skew a little higher or a little lower as compared to other studies, the overall results still point to greater research being necessary before serious improvements are made for the management of mesothelioma.

Labels: mesothelioma

posted by Belluck & Fox at 5:34 PM
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Phase II Study of Pemetrexed in Combination with Carboplatin in Patients with Malignant Pleural Mesothelioma

Tuesday, February 19, 2008

Source: Annals of Oncology

Surgery and chemotherapy represent the two most commonly delivered treatments for patients with any form of mesothelioma. While no single cure exists for this difficult disease, continuous research into improving both modalities has led to real, if still small, improvements in quality of life and overall survival time. The development of pemetrexed, marketed as Alimta® by Eli Lilly, has proven to be a watershed development in the treatment of mesothelioma. In 2004 the USFDA approved pemetrexed with the platinum compound cisplatin for the treatment of pleural mesothelioma. Since then, Alimta therapy has become the chemotherapy standard of care in the US and around the world for mesothelioma. However, the combination is known to be quite difficult to tolerate for patients with low performance scores or for those, such as the elderly, with other physical weaknesses. Because of this, scientists have been studying pemetrexed in combination with other platinum agents. Researchers from Italy have recently released their report on the use of pemetrexed with carboplatin, which is a cisplatin analogue with a lesser toxicity profile.

Introduction to the Study

The researchers enrolled 76 chemo-naive patients with histologically-proven mesothelioma in their study. Patients were included who were under 75 years old and who had measurable disease on a CT scan. Performance status had to be two or under and they must never have received prior systematic chemotherapy or had a prior cancer (excepting non-melanoma skin cancer or cervical canner in situ). There were 54 males and 22 females, with an average age of 65. Histologically, there were 57 cases of epithelial mesothelioma, 13 biphasic cases and 3 sarcomatous cases.

The study was classified as a phase II study whose primary endpoint was to evaluate the tumor’s response to the treatment. Secondary analyses included overall survival, treatment toxicity and time to progression.

Results

Three patients were classified as having a complete response, meaning all known disease had disappeared completely, and 16 patients were classified as partial responses, which means they had at least a 30% decrease in tumor burden. The combination of these two categories gives an overall tumor response rate of 25%. 29 patients were reported as having stable disease, where tumor burden was relatively unchanged (less than 30% in volume decrease or less than 20% in volume increase) while 28 others had progressive disease, which mean that tumor burden increased more than 25%.

Overall survival averaged 14 months and the median time to progression was 8 months.

As regards toxicity, the most common events were neutropenia and thrombocytopenia. The former is a potentially serious condition where an abnormally low level of an important type of white blood cell (a neutrophil) reduces the body’s ability to fight off infection, while the latter refers to a condition with an abnormally low level of blood platelets, which are an important factor in blood clotting. Overall though, the treatment was well-tolerated by most patients.

Conclusion

The authors of the study conclude that the combination of pemetrexed plus carboplatin could be an important option for the treatment of mesothelioma. While pemetrexed plus cisplatin is, and will likely remain, the chemotherapy standard of care, its toxicity profile is greater than some types of patients are able to handle and in those cases, substituting carboplatin may be the correct treatment for those patients.

Labels: mesothelioma

posted by Belluck & Fox at 4:03 PM
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Cancer ‘Coaches’ Sway Treatment Choices

Monday, February 18, 2008

Source: Yahoo! News

After the initial shock of a cancer diagnosis, one of the most difficult things for patients to do is to learn how to sift through the vast amount of data that is available about cancer treatment. Advice and support from friends and survivors can be a great benefit to patients, but the advice received may not be the best information that is available for that person and his or her personal situation. Because of this, some hospitals and cancer centers have setup a “cancer coaches” program where trained volunteers agree to work with newly diagnosed patients to help them get the right information for their diagnosis.

The key to a successful cancer coaching session is for the coach to really listen to and advocate for the patient at hand. The coaches receive training on the latest research and are expected to help the patient navigate the complex world of cancer treatment. They are there to ask questions and to give good advice about the latest options.

The three most important things a coach can provide a patient are:

1. Support
2. Resources
3. Objectivity

The third element is especially important for many patients, especially elderly or other older individuals who may be more susceptible to outside influence.

Many of these coaches are themselves cancer survivors, so their advocacy for the patient will also have a personal element to it. They can augment support groups and as long as they stay objective with the advice given, can provide a great resource to help new patients through this complex world.

Labels: cancer, mesothelioma

posted by Belluck & Fox at 10:16 AM
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Low-dose Computed Tomography Screening for Lung Cancer and Pleural Mesothelioma in an Asbestos-Exposed Population

Friday, February 15, 2008

Source: The Oncologist

Advances in imaging technologies have had a lasting impact on medical science. Better imaging techniques let doctors diagnose disease in a much more efficient manner and higher resolution scans can often be the difference between life and death. These advances are important to cancer research, especially to research in lung cancer and mesothelioma, as the ability to accurately diagnose these cancers at an early stage can dramatically improve a patient’s prognosis. An active area of research involving these two cancers involves the study of the diagnostic value of the various computed tomography (CT) modalities. Researchers from Italy have recently released the results of a study they conducted that looked at the efficacy of low-dose computed tomography (LDCT) scans for the diagnosis of lung cancer and pleural mesothelioma. The following is a summary of their findings.

Introduction to the Study

The researchers enrolled 1045 patients with a history of asbestos exposure into their study. Their aim was to evaluate the use of low-dose computed tomography (LDCT) scans for the early diagnosis of lung cancer and pleural mesothelioma. Because the link between asbestos exposure and these malignancies is well established, they expected to find a certain subset of related illnesses in some of these patients. The patients enrolled had to meet the following criteria: 40-70 years of age, no prior cancers or other severe conditions, no initial suspicion of lung cancer and no other CT scans during the previous two years.

All of the patients underwent both LDCT and chest x-ray (CXR) and the major analysis the researchers undertook was to look at how LDCT compared to CXR for the diagnosis of a thoracic malignancy.

Their results were revealing.

In nearly every way it could be, LDCT was more effective at diagnosis of lung cancer than CXR was. The researchers report detecting noncalcified nodules (early phases of lung cancer) with LDCT 19 times more frequently than with CXR. LDCT also identified 10 more full-on malignant events than CXR did.

As regards pleural mesothelioma, none of the study population at the time had developed mesothelioma, but because of its extreme latency period, this does not necessarily discount its use for the diagnosis of mesothelioma. LDCT did, however, detect a much higher percentage of pleural abnormalities than did CXR.

Conclusion

The results of this study certainly point to LDCT’s greater diagnostic efficacy for the various forms of lung cancer. The jury is still out, however, on the use of this imaging modality for the diagnosis of pleural mesothelioma, but its greater accuracy in diagnosing other pleural abnormalities is certainly a positive sign.

Labels: LungCancer, mesothelioma

posted by Belluck & Fox at 4:35 PM
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Helping the Body’s Immune System to Eliminate Cancer Cells

Wednesday, February 13, 2008

Source: Cancer Monthly.Com

The human immune system is a remarkable biological system. It heals and protects the body in so many ways that it’s very easy to overlook how extraordinarily well it functions in our everyday lives. However, it is not a perfect system and certain classes of disease do exist that can exploit its weaker points. Cancer is one such example.

While the immune system can fight off and heal many bacterial or viral infections, its inability to protect the body from the many forms of cancer has generated much research and debate. While most of the previous research on the use of immunotherapy for the treatment of cancer has yielded mixed results at best, researchers from Australia have recently released a study that shows the highly effective results of an immunotherapy experiment they performed on mice mesothelioma cells.

Introduction to the Study

The immune system is an exceptionally complex system of interacting cells and cell types, with each cell type serving an explicit function within the overall immuno-framework. When a foreign organism is introduced into the system, these various cells activate to fulfill their proscribed function. Killer T-cells are responsible for binding to antigens and removing them from the system. These T-cells are highly effective at attacking many structures, but their effectiveness against cancer has always been limited. Research into the reason why tumor cells are not attacked in the same way as foreign antigens has revealed that tumors possess a number of means of evading detection from T-cells or do not present as antigens in a manner that makes them readily bindable by T-cells.

For their study, the researchers experimented with a novel technique by injecting what are called toll-like receptor (TLR) agonists into mesothelioma cells in mice. The injection stimulated the immune system to respond to what it thought was a viral infection. The killer T-cells then attacked the tumor antigens that were the locus of the TLR injection.

Conclusion

The results were very impressive. Fully 40% of the mice saw the disappearance of all malignant tissue, while the other 60% saw some form of slowing tumor progression. While noting that anything resembling the development of human treatments was years away, the researchers are hopeful that their experiment will be studied further, both for the treatment of mesothelioma, as well as for other cancers.

Labels: mesothelioma

posted by Belluck & Fox at 12:39 PM
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Molecular Genetics and Mechanisms of Apoptosis in Carcinomas of the Lung and Pleura: Therapeutic Targets

Friday, February 8, 2008

Source: International Immunopharmacology
Volume 7, Issue 14, 20 December 2007, Pages 1934-1947

Lung cancer and mesothelioma are both devastating diseases that are often resistant to effective treatment methods. This is especially true of mesothelioma because all forms of the disease, including the most common forms of pleural mesothelioma and peritoneal mesothelioma, are without a cure, but it is also true of many variations of lung cancer as well, or of lung cancer that is only diagnosed in the advanced stages. Surgery, chemotherapy and radiation therapy remain the major modalities of treatment, but there is also an active research community investigating cellular, molecular, and gene therapies and some of the research in those fields is quite promising. As an example of these latter research fields, doctors from Australia and South Africa have recently released a report on the molecular genetics and mechanisms of apoptosis in cancers of the lung and the pleura.

Overview of the Study

Even as the overall deaths from cancer are going down in much of the industrialized world, lung cancer still accounts for the single highest percentage of deaths as compared to any other single form of cancer. Most of these deaths can be traced back to smoking tobacco or being exposed to second-hand smoke, but there are other causes of it as well: asbestos, chromates, nickel, radioactive materials and silica dust being some examples of the alternative causes. Mesothelioma is a relatively rare disease in the general public, but among asbestos workers it is not a rare disease at all. It is extraordinarily difficult to treat and no single cure exists for people who’ve been diagnosed with it. Because of these realities, research into cancer treatments probably accounts for the greatest share of medical research being done internationally.

Some of this previous research into carcinogenicity has shown a number of important cellular and molecular mechanisms at work in the development of cancer, including chromosomal aberrations and the inhibition of both tumor suppressor genes and apoptosis because of these aberrations.

Researchers have identified mutations in the tumor suppressor genes TP53 and RB as causative of cancers in the lung and pleura. The mutations lead to an inhibition of these genes’ ability to suppress tumor growth, which means that one of the body’s fundamental processes that regulates a healthy system is undermined by a genetic mutation. Another important cellular mechanism that is compromised in the development of these cancers is inhibition of apoptosis in affected cells. Apoptosis is the process by which damaged cells remove themselves from the replication cycle. In effect, it is a function of the cell to kill itself if it doesn’t meet the necessary structural components of a healthy cell. When apoptosis is inhibited, malignant cells that should have been removed from the cell cycle are not, in fact, removed, so the damaged cells continue to replicate, which puts the entire system at risk for the development of a cancer.

Therapeutic Targets

Researchers have begun to develop strategies to combat these carcinogenic activities. One of the most promising is developing chemotherapy agents that directly target the anti-apoptotic feature expressed in malignant tumors. Another strategy being researched is re-sensitizing cancerous cells to the signaling methods and molecular pathways the body uses to trigger apoptosis in affected cells.

One of the most difficult aspects of cancer research is the very nature of cancer itself: it is less a single disease than it is a family of diseases that targets specific cells in very certain ways. For example, we speak of “lung cancer” as a single disease, but in fact there are multiple forms that lung cancer can take: adenocarcinoma, non-small cell lung cancer, squamous cell carcinoma, etc., etc. The same is true for mesothelioma. There are the primary origin sites of mesothelioma, such as pleural mesothelioma or peritoneal mesothelioma, and there are also the histological subtypes of the disease: epitheloid, sarcomatous and bi-phasic. Because the individual expressions of these cancers take forms particular to certain parts of the body, research needs to account for multiple mechanisms of action in any single disease family.

The authors provide an overview of a number of possible treatment targets in addition to the ones that were discussed here. Gene therapy and the development of stem cell therapy also offer great promise for the treatment of a variety of cancers, including lung cancer and mesothelioma.

Conclusion

There is much to be excited about in cancer research these days, but the reality is that mesothelioma and lung cancer continue to take lives. Research into new modalities of treatment is always welcome and as we progress farther in our understanding of the underlying mechanisms involved, doctors and patients alike look to the day when a cure is discovered.

Labels: mesothelioma

posted by Belluck & Fox at 4:18 PM
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Radical Decortication/Pleurectomy Best Surgical Approach for N2 Malignant Mesothelioma: Presented at STS

Monday, February 4, 2008

Source: Doctor’s Guide.com

Results from a study on the efficacy of radical decortication/pleurectomy for the treatment of mesothelioma were recently released at the 44th annual meeting of the Society of Thoracic Surgeons and they showed the procedure was very successful in the treatment of the disease. The study looked at 127 consecutive patients who presented with stage 3 epithelial mesothelioma at Glenfield Hospital in Leicester, England. It found that the 55 patients who underwent radical decortication/pleurectomy had the best one-year (83%) and two-year (73%) survival rates of all the major surgical procedures used to treat mesothelioma. For the 35 patients who were treated with an extrapleural pneumonectomy, one-year survival was 55% and two-year survival was 18%. Another subgroup of 35 patients underwent vascular access thorosectomy (VATS) decortication/pleurectomy and they had a one-year survival average of 67% and a two-year figure of 22%.

The overall figures from the study showed that long-term survival was not associated with age or with sex, but was determined by the surgical method used.

Labels: mesothelioma

posted by Belluck & Fox at 9:53 AM
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