Genetics and the BAP1 Gene in Mesothelioma

dnaBAP1 is the first gene discovered in mesothelioma. Not everyone has the mutated copy of this gene and, in fact, we are just embarking on trials to try to get a better handle on the incidence.

In germ line mutations (inherited mutation), the gene is thought to be extremely rare but has some interesting associations with uveal melanoma (melanoma of the eye), renal cell carcinoma (kidney cancer) and an unpigmented nevi (a skin lesion without color). It is thought that approximately 25% of mesothelioma patients will have somatic mutations (those that occur spontaneously).  We had an entire session devoted to this at the 2013 Symposium and the full presentation is included with this post.

So why is the BAP1 gene important outside of the research realm?

It is important because we now have a gene that is being researched by a number of studies, all looking to exploit this new discovery. Currently, the research goal of the BAP1 gene is for prevention and early detection of mesothelioma. For example, asbestos exposed individuals who carry this gene can be studied to determine if a cancer signal can be picked up before the development of mesothelioma. The idea is that if you have a germ line mutation, you and your immediate family will be screened for cancers associated with this gene in the hope of picking up an early malignancy. Also, researchers will study ways to turn off this gene, if defective.

To get an even better idea about the role that genetics play in mesothelioma, the article

Mystery cancer: Inside the villages of the damned

is an excellent read. Based on research by Dr. Michele Carbone, this article discusses the mesothelioma outbreaks in Turkey and their causes.

Complementary Cancer Therapies: Helpful or Hurtful?

pill_sackEvery year, consumers spend an estimated $40 billion on complementary and alternative medicine treatments and products, with hopes of miraculous cures, often unsupported by research or by science. Some consumers affected by life-threatening illnesses, including cancer, may approach the topic of supplements or alternative therapies as an added bonus without considering the side-effects or the interactions with their prescribed treatments. Complementary therapies can be very helpful in minimizing side-effects of traditional treatments and maximizing treatment results; but they should be considered and used carefully.

wesaAt this year’s New York “Knowledge is Hope” conference, presented by the Mesothelioma Applied Research Foundation, Kathleen Wesa, MD of Memorial Sloan-Kettering Cancer Center, focused on complementary therapies used in conjunction with mainstream treatments for cancer patients. We listened to Dr. Wesa’s talk once before, at our 2009 Symposium, and have jotted down a few interesting points from her talk.

Cancer patients, in particular, should know that using complementary therapies  could interfere with, and in certain cases even destroy, the benefits of traditional treatment. Antioxidants such as Vitamin C, widely available in supplement form and aggressively marketed as “cancer fighters”, can actually prevent patients from fully benefiting from chemotherapy. In mesothelioma specifically, the one FDA-approved chemotherapy, Alimta, operates as an anti-folate. Overuse of the common “daily supplement,” folic acid, can actually block Alimta’s therapeutic benefit. This is a risk no mesothelioma patient should undertake blindly.

On the other hand, other complementary therapies used in conjunction with mainstream treatments have been found to be helpful. For example, for cancer patients undergoing chemotherapy, a study from the University of Rochester in New York has shown the effectiveness of ginger in relieving nausea.

Adding an exercise routine and paying close attention to nutrition have both been shown to greatly benefit cancer patients. The World Cancer Research Fund International recommends daily exercise in excess of 30 minutes and a diet prevalent in foods of plant origin, limiting sugary foods and drinks. Meditation, yoga, tai-chi and other “alternative” types of mind-body practices used by cancer patients also show benefits against pain, anxiety and insomnia.

The bottom line for mesothelioma patients: before shelling out money for the latest alternative or complementary “cure,” investigate carefully and consult with your physician or other medical expert. Dr. Wesa’s video presentation from our Symposium can be viewed here.

UPDATES FROM IMIG: Part 2, Thursday, September 13, 2012

  • In a talk concerning adjuvant radiation following EPP, it was stated that radiation oncologists who are inexperienced may not give as high a dose or may shy away from difficult areas.  It was felt to be important based upon lower local failure in centers with expertise in radiation oncology.  Concern was expressed about patients having radiation locally and perhaps this needs to be emphasized at the time of the initial surgical consult.  This is an important take home message and reason to explore accommodations where there is expertise early in the process.
  • Dr. Joseph Friedberg presented on his current approach using photodynamic therapy. Dr. Friedberg has been championing this procedure over the past few years and has discussed that he does a “radical pleurectomy” coupled with photodynamic therapy.  Photofrin, which is the agent used in this light-based therapy, has recently received orphan drug status. This procedure will not be offered to non epithelial patients.  Dr. Friedberg agreed with one of the earlier speaker that node 2 disease patients benefit from this procedure.  It has been noted that pleurectomy decortication is not a standardized procedure and there are variations among the surgeons. There has been discussion at this conference and others about the need to standardize these approaches so that we can compare series of patients with confidence that we are comparing results of the same procedure.  There are plans underway to do a randomized trial (eliminates investigator bias) to determine if PDT is superior to a radical pleurectomy without PDT.  Will keep you posted when this trial gets underway.
  • Polymeric films are under investigation as a new method to deliver drugs directly to the chest cavity.  The films facilitate increased drug penetration in comparison to Cisplatin solution for prolonged periods of time. Animal models of these polymeric films containing Cisplatin demonstrated ease of application, ability to cover the pleural space ability to reach highly concentrated drug in comparison to intravenous or intra-pleural Cisplatin.  This new approach also appears to be associated with less kidney toxicity.  Work is ongoing and anticipated that it have applicability in mesothelioma patients in the next few years.
  • Dr. Paul Sugarbaker was the first speaker in the session about peritoneal mesothelioma.  He stated that the median survival is now at 10 years, with about 1/3 of the patient requiring another surgery at some point during the course of the disease.  Dr. Sugarbaker currently has a new protocol which he spoke about using bidirectional treatment where surgery is performed and then for 6 months following surgery patients will receive 6 additional cycles of chemotherapy both IV and intraperitoneal via ports placed into the abdominal cavity.It was discussed that patients who recur in the chest have surgery and rarely recur again in the chest cavity.  He was congratulated by chest surgeons who are striving to replicate these results in pleural mesothelioma.
  • Dr. Steven Albelda, a member of our SAB, spoke about immunotherapy in mesothelioma and mentioned the large number of immunology trials taking place in mesothelioma.  Passive immunotherapy use of antibodies to treat cancer – antibodies can inhibit signaling pathways or can coat malignant cells making them targets for drugs or be immunotoxin for example SS1P at the NCI. Mesothelin is highly expressed in many cancers and has become a target in a number of mesothelioma clinical trials.  Soluble mesothelin can be used as a biomarker (Mesomark).Amatuximab (anti mesothelin antibody) given in combination with Pemetrexed and Cisplatin will be moving into a randomized trial at least that is the underlying buzz at this conference.Some trials were reported using immunotherapy in small number of patients which appeared to result in prolonged stability after initial response.Many of us of heard of Provenge being approved in prostate cancer we also have vaccines now being studied in the clinics. In the Netherlands they are investigating dendritic cell vaccines, at MSKCC we are looking at the WT1 vaccine both initially funded by the Mesothelioma Foundation.UPenn has a t cell vaccine which is being offered to patients who have failed prior therapy.

    The presentation ended with a  discussion with the use of gene therapy which is under investigation at UPenn. The gene therapy utilizes an adenovirus to stimulate the immune system.

UPDATES FROM IMIG: Part 1 – Thursday, September 13

  • Dr. David Sugarbaker spoke about the effectiveness of surgery and some of the adjuvant therapies that can be used to clean up the surgical site or to combat recurrent disease. We heard about biologics, photodynamic therapy, and there will be sessions later today on intracavitary heated chemotherapy during surgery, and then more on staging, imaging, chemotherapy and immunotherapy.  There will be a dedicated session for peritoneal mesothelioma.
  • In the early afternoon, the Meso Foundation will be hosting a lunch where Meso Foundation funded grantees will present their work. All of our grantees’ posters were selected to discuss their work in sessions throughout this meeting, thus highlighting the ability of our Scientific Advisory Board to identify promising new research.  This is only possible due to the generous donations of our mesothelioma community.
  • There has been some heated debate during this meeting about the differing surgical options of EPP vs. PD or even if surgery should remain an option.  Those attending the meeting have a focused dedication to irradiating mesothelioma and this debate moves the field forward.
  • Question under discussion during the surgical session: Is it better to treat neo-adjuvant (chemo before surgery) or post- surgery.  Seems there might be a light advantage using neo-adjuvant but the evidence is not strong so it remains surgical choice.
  • Yesterday we learned that histology can change in approximately 20% of the cases – larger samples allow for more accurate diagnosis of histologic subtype.  Another reason why we describe mesothelioma as a disease best staged and described through surgery.
  • What factors are relevant for treatment decision?  Role of mediastinoscopy – perhaps we need to rethink nodal status as some with lymph nodes (N2) still did well following surgery though the numbers were small. Discussion ensued that with larger numbers there would be a demonstrable difference. It was suggested that this group (those with nodal involvement) may benefit from neo-adjuvant chemotherapy.
  • Tumor volume has prognostic value. We can measure this on scans and the evidence is solid. It has been suggested that we factor this in.
  • Waiting for the discussion of the IASLC Mesothelioma Staging Project which will take place this afternoon.

Intro to iMig: iMig and the Meso Foundation

What is iMig?

In the next week and a half, you will be hearing a lot about the iMig meeting. This may leave you with a few questions, first one of which probably being “what is iMig?”

The International Mesothelioma Interest Group (iMig) is an independent international group of scientists and clinicians working to understand, cure and prevent mesothelioma. The group was started in 1991 and has since then been the organizer of bi-annual meetings meant to facilitate the sharing and collaboration of researchers and doctors interested in the study of mesothelioma and its potential treatments.

The Mesothelioma Applied Research Foundation and iMig share a productive history. In fact, many Meso Foundation grant recipients and Foundation’s Science Advisory Board members are also members of iMig. For example, the current chair of iMig, Dr. Steven Mutsaers is also an esteemed member of the Meso Foundation’s Science Advisory Board. In 2006, the two organizations hosted a joint meeting in Chicago, IL, and if you’ve ever attended a Meso Foundation Symposium, you may have noticed that many of our speakers are also collaborators of iMig.

iMig 2012 Meeting in Boston, MA

This year, iMig is hosting its bi-annual meeting in Boston, MA, and the Meso Foundation will, once again, be represented. Our own nurse practitioner and executive director, Mary Hesdorffer, MS, APRN, will co-chair a session, while another session will be dedicated entirely to our grant recipients who will present the findings of their Meso Foundation-funded research.

While most iMig members are well-aware of the Foundation’s prestigious peer-reviewed research program and many of them have applied for funding, the Meso Foundation will also take this opportunity to further promote its research program in our effort to obtain the most promising project applications available to speed up treatment development and to ultimately find a cure for mesothelioma.

As the meeting begins on September 11, we will keep you posted on current developments and updates from Boston.

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