Topic: Asbestos

The Researcher and the Clinician – “Translational Research”

“We are used to work[ing] with molecules, with cells,…with experimental animals, while…physicians are used to work[ing] with real live patients, and of course we use different…[terminology] sometimes…[In] some cases, collaboration is very useful and successful, and we can say, especially for us [who are] used to working in…the labs, [it is exciting] to meet the patients that are surviving or doing better.  Even small improvements are very important to us.  It’s…a very interesting and emotional experience.” – Giovanni Gaudino

Researchers and clinicians inhabit two very different worlds.  The researchers work with cells and molecules in their laboratories, and usually do not see the patients that they are trying to help through their research.  The physicians, on the other hand, care for their patients in clinic and hospital settings, and often get to know their patients intimately.   But communication between these worlds – the world of the researcher in the laboratory and the world of the physician who is caring for their patient – is becoming more and more important.
As researchers become increasingly aware of their role in communicating the results of their research to physicians, the physicians, in turn, can “translate” the results of this research into new and effective therapies.  Thus it becomes “translational research.”  The clinicians’ feedback is also very important to the researchers, who learn how the patients are doing and how they are responding to the new therapies.  This makes it possible for the laboratory researchers to adjust and revise their work.

This communication between researchers and physicians or “bench to bedside” approach is not always easy.  This can be difficult because they sometimes seem to use different languages as they talk in technical terms specific to their field of expertise.  However, the patient is at the very center of this collaboration and is the most important reason that this strong effort toward enhanced communication is being made.  On the occasions when the researcher has the opportunity to meet patients and to know how they are doing, this too can be very inspirational and motivational.

The Researcher and the Mesothelioma Patient

“I saw patients with incredible increasing quality of life…And to see that what we are doing could help individuals to feel…better is something very, very special that I’ve never experienced before.” – Giovanni Gaudino

Most of us do not think of research scientists having any contact with patients.  Ordinarily, research scientists do not have a chance to meet mesothelioma patients during clinical trials.  When clinical trials begin, the researchers “step back.”   However, in some instances, basic scientists do meet these patients.  Dr. Giovanni Gaudino has had this wonderful opportunity.  He describes this as an emotional experience because he saw the improvement in the mesothelioma patients’ quality of life, regardless of whether the therapy was successful in getting rid of the cancer or just stabilizing the disease.  These patients were happy, they were active, and they also recognized the importance of the work going on in the laboratory.  Dr. Gaudino explained that this was a very powerful emotional experience to see that as research scientists, they were helping these patients.

Well known approaches to cancer treatment include surgery, radiation therapy, chemotherapy, immunotherapy, and chemicals.  All of these conventional therapies have been and are still being used to treat mesothelioma.  While some of these approaches have been successful with other solid tumors, unfortunately, this has not been the case with mesothelioma.

“All these agents can kill cells. . . .  Unfortunately, this is not true for mesothelioma, because, as I say, it is a very resistant tumor to … conventional therapy.  So, because of that, we try to find … new therapeutic approaches.” – Giovanni Gaudino

One of these important new approaches is aimed at overcoming chemoresistance and interfering with cell survival.

Overcoming Chemoresistance

Scientists like Dr. Gaudino have been studying how mesothelioma cells develop; in other words, what has gone awry in the normal cell life of growing, maturing and then dying off.  Dr. Gaudino points out that the growth signals that lead to cancer cell proliferation and neoplastic transformation are the result of a series of biochemical reactions that start at the cell’s surface and move down in a multi-step process called “receptor downstream signaling.”  This continues until the signals reach the nucleus of the cell and their final destination, which is the DNA.  The DNA is the “port master” of all that is going on in the cell.  The “big button” on the top of the cell membrane is called the “Receptor Tyrosine Kinases.”  It mediates the process by which cells become resistant to cell apoptosis, or what is known as “programmed cell death.”  Apoptosis is a normal process of getting rid of old cells.  In an average adult human, 50 to 70 billion cells die every day as a result of apoptosis.  In patients with mesothelioma as well as other cancers, there is insufficient apoptosis, and there is cell proliferation of abnormal cells.

“So the rationale of our work was that the Receptor Tyrosine Kinases, which is the big button that you see on top of the handle of the cell membrane, can be a good target, and by inhibiting [the] receptor downstream signaling . . . we could get rid of the tumor chemoresistance.” – Giovanni Gaudino

The purpose of the drugs used to target this button, then, would be to interfere with cancer cell survival and chemoresistance.

Cell Survival

There are many different molecules involved in cell survival and apoptosis.  These molecules are on the surface of the cell, in the interior of the cell, and in the nucleus.  These molecules all have names so that they can be identified.  Thus, if someone is exposed to asbestos, this toxic exposure combines with genetic factors and many other different reactions.  These different reactions are all pathways that determine cell survival and the transformation of normal tissue to tumor cells which results in cancer, in this instance, malignant mesothelioma.

“And, cell survival is a very important step for a cancer, because if [a] cell can survive despite all the DNA mutations, the DNA damage they suffer, it means they have a good chance to become tumor cells and to .. [become] cancer.” – Giovanni Gaudino

As you or your loved one is considering the course of treatment for mesothelioma, you and your physician will need to explore the possibility of enrolling in a clinical trial as a critically important option.  A clinical trial is a study to evaluate new treatments to determine how effective and safe a certain medication, combination of medications, a surgical or radiation procedure or a combination of these modalities might be.  Patients enrolled in clinical trials are monitored closely.  These clinical trials allow medical research to progress, so that diseases once thought to be incurable are now curable.

Misconceptions About Clinical Trials Dispelled

Having never made such a monumental decision, many are concerned about enrolling in a clinical trial.  Some worry that the patient will be treated like a guinea pig or will receive the placebo or sugar pills.  Worse yet, some think that clinical trials should be considered only when there is no hope.  These misconceptions about clinical trials are dispelled at the International Mesothelioma Program (IMP) at Brigham and Women’s Hospital in Boston, Massachusetts.

Dr. David Sugarbaker, the founder and director of the International Mesothelioma Program and the Chief of Thoracic Surgery at Brigham and Women’s Hospital, has been treating mesothelioma patients along with his colleagues at the Dana-Farber Cancer Institute since the 1980s.  In fact, the clinical trials being conducted at the IMP are at the forefront of state-of-the-art mesothelioma treatment and care in the United States.  Each year approximately 160 mesothelioma patients are treated at the International Mesothelioma Program by Dr. Sugarbaker and his team of medical experts.  Twice that number of patients are seen for consultation.

Surgical Clinical Trials Leading to Increased Survivability

In a lecture given in late 2009, Dr. Sugarbaker noted that through his surgical clinical trials, the IMP is seeing a 17 percent survival rate for patients who are four years post-surgery.  This is remarkable when you consider these patients’ original prognosis, which was a mere six to nine months to live.  Dr. Sugarbaker is seeing survivors who are eight to ten years post-surgery and a few others who are living as long as 13 years with no recurrence.

Attorney L. Richard DeRobertis who has represented mesothelioma clients for decades, is very hopeful when he see the results Dr. Sugarbaker has had from his clinical trials.

“I have seen my clients suffer and die from this devastating cancer.  Dr. Sugarbaker’s clinical trials portend much hope and promise that one day in the not so distant future mesothelioma will be a curable disease.”

Clinical Trials at the International Mesothelioma Program

One important mesothelioma clinical trial is Protocol 07-091 for patients with resectable pleural malignant mesothelioma; that is, a tumor that can be removed surgically.  The surgery is followed by heated chemotherapy drugs applied directly into the chest cavity during the surgical procedure.  The drug combination used is Cisplatin along with Gemcitabine.  Amifostine is also used to protect the normal cells.  The patient is then followed weekly.

Of 304 patients screened, Dr. Sugarbaker says 64 were enrolled in this clinical trial.  The study is still open and accepting patients.  The clinical trial requires that certain criteria are met in order for a patient to qualify for enrollment in Protocol 07-091.  Since time is of the essence, it is important that patients discuss this and other possible courses of treatment with their physician right away.   They may also consider calling the IMP directly at phone:  617-732-5922 to get immediate information.

It is clear that through a number of clinical trials, medical advances are taking place at the International Mesothelioma Program under Dr. Sugarbaker’s leadership.  Virtually all advances in cancer treatment involve clinical trials.  These advances translate to hope and a prolonged and enhanced quality of life for mesothelioma patients.

New Clinical Trial Underway

The International Mesothelioma Program will be conducting a new clinical trial for patients with advanced stage mesothelioma.  This new Phase I trial would use the neoadjuvant mTOR inhibitor followed by administering Cisplatin in combination with pemetrexed or Alimta.  After the chemotherapy regimen, depending on the patient’s response, an extrapleural pneumonectomy could then be performed.

Over the years through the clinical trials, the IMP has been able to increase the dose of chemotherapy drugs to the maximum tolerable amount.  Additionally, because of Dr. Sugarbaker’s experience treating so many mesothelioma patients, he and the IMP have learned the site of recurrence of the cancer is usually in the chest or abdomen where the original tumor appeared.  Dr. Sugarbaker explained that he and his medical team have observed over the last 15 years that, even after surgery, microscopic cells are present and thus he developed the in vivo model, as he calls it, of administering the heated chemotherapy in the maximum tolerable dose into the open chest cavity.

His patients have words of praise and gratitude as they speak of Dr. Sugarbaker being a hero and a pioneer in mesothelioma research with the clinical trials which the International Mesothelioma Program is conducting.

When faced with a life-threatening diagnosis of malignant mesothelioma, the patient and his or her loved ones will certainly seek the most advanced medical care to ensure the best possible outcome.  Memorial Sloan-Kettering Cancer Center is at the forefront of such cutting-edge medical research and care for mesothelioma patients.  Dr. Lee M. Krug, a thoracic oncologist, is the Director of the Mesothelioma Program at Memorial Sloan-Kettering Cancer Center (MSKCC).  With its main campus and inpatient hospital located in Upper East Side Manhattan, Memorial Sloan-Kettering also has about a dozen outpatient clinics in New York City, Long Island and New Jersey where mesothelioma patients can receive their chemotherapy and radiation treatments at these community-based locales.

Multi-Disciplinary Team Serves Mesothelioma Patients

If you decide to contact Sloan-Kettering, you may want to consider the option of entering one of several mesothelioma clinical trials for treatment and care.  This consideration will be carefully discussed with a physician or nurse clinician at Sloan-Kettering who is part of a multi-disciplinary team.  This team of specialists will be there to serve you and meet your medical needs, as well as your emotional and other needs, as you go forward with your treatment and care for mesothelioma.

Consider Entering A Mesothelioma Clinical Trial

Under Dr. Krug’s leadership, there are presently at least three open mesothelioma clinical trials being conducted at Sloan-Kettering.  One trial utilizes an investigational drug known an CBP 501, a stable peptide, which is an enzyme that works on cancer cell division.  Along with CBP 501, the standard mesothelioma therapy of Alimta and Cisplatin is used.  In order to participate in this particular study, the mesothelioma tumor must be unresectable and untreated.  The mesothelioma patient must also be able to be up and about for half of his waking hours.

Another clinical trial involves the use of Everolimus (RAD 001).  Everolimus inhibits the molecule mTOR which helps cancer cells grow.  Even if a mesothelioma patient has had prior chemotherapy treatment, he or she can still participate in this study.  The patient will need to have adequate pulmonary function however.

Finally, another trial is a toxicity study utilizing chemotherapy followed by Intensity Modulated Radiation Therapy (IMRT), which is targeted radiation.  To participate, the mesothelioma patient must have an unresectable tumor and not have had any prior chemotherapy or radiation treatment.  Usually standard radiation therapy does not work well for mesothelioma patients.  Some radiation oncologists liken it to attempting radiation on the apple peel without radiating the apple itself.  IMRT obviates this problem of standard radiation therapy.

Of course eligibility for any of these mesothelioma clinical trials will be decided in close consultation with the multi-disciplinary team who will review each individual mesothelioma patient’s medical records, test results and situation very carefully.

Be Proactive – Explore Sloan-Kettering’s Mesothelioma Program

As you can see, if you intend to explore the possibility of participating in any of these mesothelioma clinical trials, the sooner you contact the Sloan-Kettering Mesothelioma Program, the better it is for you.  More options may be available.

Attorney Richard DeRobertis, who has represented many mesothelioma clients over three decades, remarks that, “from a scientific point of view, what is happening at Memorial Sloan-Kettering is exciting and encouraging.  But more importantly, from seeing what my clients and their families have gone through over the years, I encourage anyone who has been diagnosed with mesothelioma to be proactive and explore what is available at leading cancer centers such as Sloan-Kettering.”

Galiher DeRobertis & Waxman has represented clients with mesothelioma and lung cancer resulting from asbestos exposure for the past 30 years.   Some of our clients have participated in clinical trials that test new combinations of surgery, radiation and chemotherapy drugs.  Our clients also have benefited from the advances and new discoveries made through the study of other types of cancer.
Researchers are always looking for new ways to battle cancer.  We know that new approaches, research, and discoveries related to all types of cancer can play an important role in finding better treatments, and eventually a cure for mesothelioma and lung cancer.  The chemotherapy drug Cisplatin, for example, was used against various types of cancer since the 1970s.  However, clinicians eventually combined Cisplatin with Alimta and found that it was an effective treatment against mesothelioma.  Mesothelioma patients lived as much as 30% longer when treated with this combination, and it was made possible by the discoveries and advances made against other forms of cancer.

For years Mina Bissell, Ph.D., of the Lawrence Berkeley National Laboratory and others have pushed hard to emphasize the point that studying and understanding the cellular environment of cancer is as important as understanding gene mutations and alterations.  Which for the most part, has received the majority of researchers’ attention thus far.  As a result of their efforts, many researchers are now looking to study a tumor’s environment.  Scientists increasingly believe the interaction between cancer cells and the surrounding cells and tissue may reveal important information for eventually finding ways to prevent cancer.

Normal Cells May Be Responsible for Allowing Cancer to Escape

Autopsies often find tumors in people who die from something other than cancer.  However, these tumors go unnoticed because they were not causing noticeable symptoms.  Researchers believe that the tumor’s environment may play a big role in helping to keep these tumors in check.

Researchers are looking at normal cells to possibly explain why a tumor becomes lethal, rather than focusing solely on the tumor itself.  Researchers are also looking at factors that may affect normal cells such as aging and chronic liver inflammation that can change the normal architecture of cells or cause them to crumble.  The idea is that cancer may spread and become lethal because normal cells allow cancer cells to escape and thrive.

How a Cancer’s Environment Responds May Fuel Its Growth

In addition to allowing cancer cells to escape and spread, a tumor’s environment also plays a big role in fueling its growth.  Studies are now underway to show how cancer cells are able to signal surrounding cells (or cell signaling pathways) in a way that promotes cancer growth.  Genentech, a biotechnology company that is part of the Roche Group, is currently testing a new drug to interrupt this type of signaling.  The theory is that some tumors cannot successfully spread without the cooperation of the surrounding cells, so some types of cancer may be successfully treated by focusing on the cancer’s environment.

Focus on Cancer’s Environment Causes Researchers to Also Look Elsewhere

Many new studies have begun to focus on cancer growth factors that were previously dismissed.  For example, researchers are looking at the relationship between injuries and cancer growth.  There are many reports that cancer becomes more aggressive after surgery or some other traumatic injury, and researchers like Dr. Bissell are still developing evidence to support or disprove these theories.

Obviously, research in these areas will continue to help researchers better understand cancer.  These new approaches have not yet led to any cures, but researchers and scientists are hopeful, even though success may be years away.

We Support Research To Find Better Treatments For Cancer Patients

Galiher DeRobertis & Waxman is committed to supporting research to help find a cure and better treatment for lung cancer, mesothelioma and asbestosis.  Our law firm has helped many clients and their families obtain compensation for asbestos-related illnesses.

Through our legal work, we also collaborate with cancer researchers and institutions.  We are very encouraged by their efforts to develop better treatments, and we support researchers who are finding new approaches to fight cancer and other terrible diseases.

Today, cancer is the leading cause of death worldwide.  It is estimated that the number of cancer deaths around the world is expected to rise by 45 percent between 2007 to 2030.  However, experts now claim that as many as 40 percent of cancers could be prevented by protecting against infections and by making lifestyle changes.

Experts Give Ways To Prevent Cancer

A report by the International Union Against Cancer (UICC), a non-governmental organization based in Geneva, highlighted infections that can possibly lead to cancer.  The report accentuated the importance of vaccines and lifestyle changes.

David Hill, the President of the International Union Against Cancer, stated that we now have the knowledge to prevent approximately 40 percent of cancers, but tragically, we are not using it.

International Union Against Cancer Urges Government And Policymakers To Take Action Now

The International Union Against Cancer emphasized the importance of using the vaccines that we now have for human papillomavirus (HPV), which can lead to cervical cancer, and hepatitis B, which can lead to liver disease and cancer, as well as other illnesses that can be prevented with vaccines.

Other diseases that can also lead to cancer such as human immunodeficiency virus (HIV), hepatitis C and Epstein Barr have no vaccines.  However, the International Union Against Cancer has made a call to policymakers to educate their communities so that preventive measures can be taken and simple changes in lifestyle can be made.  Simple changes that would be of benefit include smoking ceasation, alcohol intake limitation, and sun exposure reduction.

As part of an effort to better educate communities and have governments and policymakers take preventive measures, the International Union Against Cancer launched their “Cancer Can Be Prevented Too” campaign on World Cancer Day, February 4, 2010.

Adequate Warnings Could Have Prevented High Incidence of Mesothelioma

Today, we are grateful that many experts are focusing on prevention and education as well as better treatments and cures for all types of cancers.  For more than 30 years, the Galiher law firm has been successfully representing clients who have contracted mesothelioma, a deadly form of cancer caused by exposure to asbestos, that could have been prevented if adequate warnings had been given and safety measures taken.  We know that exposure to asbestos is the cause of mesothelioma, and that many asbestos-related illnesses could have been prevented if civilian shipyard workers and military personnel on U.S. Navy ships and submarines had been adequately warned of the dangers of asbestos.  However, our clients were not provided with the information they needed to take necessary precautions to protect themselves.

In addition, others who lived near asbestos factories or mines were never educated as to the dangers of asbestos and never had the opportunity to take precautionary measure to protect themselves, and as a result, many have suffered from asbestos-related illnesses.  Due to bystander exposure and environmental exposure,  many unwary people have contracted and suffered from asbestos-related diseases.  Unfortunately, the asbestos manufacturers knew of the hazards of asbestos but concealed their knowledge and continued to sell their products, resulting in an ongoing tragedy of people being diagnosed with mesothelioma and lung cancer.

Malignant mesothelioma is a rare disease in the general population.  About one person per million contracts this aggressive cancer, which is caused by exposure to asbestos products.  By way of comparison, about 215,000 people were diagnosed with lung cancer in 2009 versus about 3,000 who were diagnosed with mesothelioma.  As a result, the ability for research scientists to rapidly gather data about the disease is limited by the number of patients seen by the researcher’s facility.  Fortunately, the International Mesothelioma Program (IMP) at the Brigham and Women’s Hospital in Boston has helped to solve this problem and advance research in this area because of its extensive tumor bank and patient registry.

International Mesothelioma Program Shares Tissue Samples to Advance Research

The International Mesothelioma Program, under the leadership of Dr. David Sugarbaker, sees approximately 300 mesothelioma patients for consultation each year.  Last year, over 160 of these patients also underwent surgery.  The IMP maintains a patient data registry as well as a tumor bank of all patients who are seen at Brigham and Women’s Hospital for mesothelioma treatment.  Because the International Mesothelioma Program works collaboratively with the Dana-Farber Cancer Institute, mesothelioma patients treated at any of these facilities become part of this important patient data registry.  If surgery is performed, their pathology material is preserved in the International Mesothelioma Program’s tumor bank as well.

There is significant research underway at the International Mesothelioma Program using the tissue samples and the data from the patient registry.  However, the IMP also recognizes the importance of advancing  mesothelioma research in other hospitals and cancer institutes.  Accordingly, the IMP readily shares the information in the patient data registry and the tissue samples from the mesothelioma tumor bank with researchers at other cancer centers to advance the study of the development of mesothelioma and how to treat this disease.

One such researcher is Dr. V. Courtney Broaddus, a professor of medicine at the University of California at San Francisco.  Dr. Broaddus is studying the role played by other cells such as immune cells around the mesothelioma cells.  She studies macrophages to understand the role they play in assisting the mesothelioma tumor’s growth.  To do this research, the IMP sends tumor tissue to Dr. Broaddus via Federal Express from tumors that are resected from patients.  After the overnight flight from Boston to San Francisco, the tumor cells are still alive when they arrive.  Dr. Broaddus commented that this just shows how tough and hardy these mesothelioma cells are.  She grows these cells in vitro to observe the growth of the macrophages.  Growing these cell lines also enables her to test various treatments on mesothelioma cells.

Research Comparing Surgical Results Based On Patient Age

Although the International Mesothelioma Program was officially formed in 2002,  a patient data registry has been maintained for many years because patients have been treated at the Brigham and Women’s Hospital for mesothelioma since the 1980s.  The database has 400 fields, so all kinds of information has been captured and recorded for 2,000 patients.

One example of the type of research that has been conducted involves a study done by Dr. Andrea Wolfe of the IMP and Brigham and Women’s Hospital.  Dr. Wolfe compared the outcomes for mesothelioma patients having either an extrapleural pneumonectomy or a pleurectomy with decortication and were 65 years old and older.  She found that older patients fared less well immediately after the extrapleural pneumonectomy, but in terms of longer term outcomes of those who survived the surgery, both surgeries produced similar results.  She was able to do this research retrospectively looking back at 227 patients who were in the patient data registry.

Attorneys Recognize Valuable Resource for Mesothelioma Research

Attorney Richard DeRobertis, who has successfully represented hundreds of mesothelioma clients, remarked that the IMP’s patient data registry and tumor bank are, “an incredibly valuable resource for scientists so they can do cutting edge research that will eventually lead to a cure for this devastating disease.”   While DeRobertis and his law firm Galiher DeRobertis & Waxman have been able to obtain fair compensation for their mesothelioma clients and their families, the untold suffering caused by mesothelioma can only be addressed by medical research being done by Dr. Sugarbaker, the IMP and other scientists.

Lung cancer, like asbestosis and mesothelioma, can be caused by exposure to asbestos.  Many who suffer from lung cancer and mesothelioma have to undergo invasive procedures when being diagnosed.  However, new procedures are being developed to test for lung cancer and may help trigger the development of similar tests for other cancers.

Promising New Lung Cancer Detection Test

Steven Dubinett, M.D., is the senior author of a study presented at the American Association for Cancer Research – International Association for the Study of Lung Cancer’s (AACR-IASLC) joint conference in California that may change current diagnostic procedures.

Dr. Dubinett is the director of the Lung Cancer Research Program at the Jonsson Comprehensive Cancer Center at the David Geffen School of Medicine, University of California, Los Angeles (UCLA).  He stated that approximately one in every 500 x-rays shows a lung nodule of “indeterminate significance.”  When that occurs, a physician will order a biopsy or insert a scope into the lungs for further review.  However, Dr. Dubinett says that new research has discovered and assembled 40 biomarkers made up of proteins that can be used to detect lung cancer.  A biomarker or biological marker, is a substance in the blood that can be detected and measured with blood tests.  In this case, the biomarkers being tested are the proteins believed to contribute to lung cancer, or the proteins that change when cancer exists.

Status Of New Detection Test

The new procedure, however, is still in the developmental stages.  It will likely take years before it is clinically available.  If successful, the tests will also likely be able to detect lung cancer in early stages.  As with many other illnesses, early detection can help raise survival rates significantly.

Through clinical trials and research, clinicians and researchers will continue to gain a better understanding of how cancer develops, and new procedures will continue to be developed to help provide better care for those who suffer from these diseases.

We Support Research To Find Better Detection And Treatment For Cancer Patients

Galiher DeRobertis & Waxman is committed to supporting research to help find a cure and better treatment for lung cancer, mesothelioma and asbestosis.  For over 30 years, our law firm has helped our clients and their families obtain compensation for asbestos-related diseases.  We know a diagnosis like lung cancer can be devastating, and we know from our clients how uncomfortable and stressful diagnostic and treatment procedures can be.

Through our legal work, we collaborate with cancer researchers and institutions, and we are very encouraged by their efforts to develop new detection methods and treatments, and to eventually find a cure for these terrible diseases.