Pass_subbed.qxp 26/11/08 03:03 Page 60
Malignant Mesothelioma
Malignant Pleural Mesothelioma—A Current Review
a report by
Marc S Ballas, MD,
1
Abraham Chachoua, MD,
2
Jessica Donington, MD
3
and Harvey I Pass, MD
4
1. Medical Oncologist; 2. Associate Professor of Medicine and Urology; 3. General Thoracic Surgeon; 4. Professor of Cardiothoracic Surgery and Surgery, and
Division Chief, Thoracic Surgery and Thoracic Oncology, New York University School of Medicine
Malignant pleural mesolthelioma (MPM) is a locally aggressive cancer that In addition to the direct costs to the healthcare system, defendant companies
arises from the multipotential mesothelial cells of the pleura. MPM has a in the US have already paid $54 billion in legal claims and are expected to
uniformly poor prognosis with a median survival from diagnosis of nine to face upwards of $200 billion in future liabilities, thus representing a
12 months.
4
Limited treatment options are available for those diagnosed significant socioeconomic burden.
5
Interestingly, only 5% of asbestos mine
with MPM or at risk for developing MPM from past or ongoing asbestos workers who have experienced heavy exposure to asbestos go on to develop
exposure. While rare, MPM is responsible for approximately 0.6% of all MPM, a fact that illustrates the complex relationship between environment,
cancer-related deaths.
5
MPM poses an increasing public health, medical, biology, and genetics in MPM.
10
In addition, the characteristically long latency
and economic problem. This is due to the peak commercial use of asbestos time for developing MPM suggests that the multiple somatic abnormalities
in industrialized countries between the 1930s and the 1960s and the common in MPM accumulate within the mesothelial cells over time and
latency in developing MPM from the time of first exposure, which ranges contribute substantially to the pathogenesis of MPM. Recent research has
from 15 to 40 years.
6,7
In addition, asbestos continues to pose a public implicated multiple molecular pathways and genetic loci that are abnormal
health hazard throughout the world due to the need for its disposal and its in MPM, and has increased our understanding of the pathogenesis of the
current and increasing use in industrializing nations. Recent estimates report disease. These insights may provide possible therapeutic targets for
an expected incidence of 2,000–3,000 cases per year in the US, treatment and prevention.
1,950–2,450 cases per year in the UK, and 250,000 deaths caused by MPM
in Western Europe over the next few decades.
1,8,9
Pathogenesis
The mechanism of asbestos-induced MPM is unclear. Genomic and molecular
analyses have elucidated multiple cytogenetic and molecular abnormalities that
Marc S Ballas, MD, is a Medical Oncologist at New York University
(NYU) School of Medicine and NYU Cancer Center. He is on the
contribute to the development of MPM. It is commonly believed that asbestos
Faculty of Medicine at NYU School of Medicine, with a clinical inhalation leads to the deposition of fibres deep in the lung parenchyma and
research interest in thoracic tumors and sarcoma. His main focus is
eventual migration and implantation of fibers into the pleural lining. Repeated
the diagnosis and treatment of non-small-cell lung cancer,
including the investigation of novel agents of therapeutic and
episodes of inflammation and healing, oxygen free radical production from
preventive potential in clinical trials. Dr Ballas completed his inflammatory cells and the iron moiety within asbestos,
11–13
and direct damage
medical oncology training at the Medical Oncology Branch of the
to DNA by the fibers are generally accepted pathogenic features of asbestos
National Cancer Institute in Bethesda, Maryland.
exposure.
4
Interestingly, dose-dependent cytotoxicity of asbestos is not lethal to
Jessica Donington, MD, is a General Thoracic Surgeon at New York the asbestos-sensitive mesothelial cells.
14,15
The inflammatory response to
University (NYU) School of Medicine. She is Director of the NYU
asbestos deposition in the pleura is mediated by macrophages and mesothelial
Thoracic Oncology Translational Laboratory at Bellevue Hospital,
and her clinical and research interests are focused on the
cells, with both cell types secreting tumor necrosis factor (TNF)-α and the
diagnosis and treatment of non-small-cell lung cancer. Her areas mesothelial cell expressing TNF-α receptor (TNF-R1) in an autocrine and
of clinical expertise include the use of multimodality therapy for
paracrine interaction. TNF-α then stimulates the nuclear factor kappa B (NF-κB)
lung cancer and lung cancer in women. Her laboratory work looks
at the detection of biomarkers for the early diagnosis of lung
pathway, which regulates pro-survival cellular mechanisms and may allow
cancer and at the role of osteopontin, an ubiquitous protein, in asbestos-induced DNA-damaged cells to divide rather than undergo apoptosis.
lung cancer development.
This response imparts a survival advantage that permits the asbestos-injured
Harvey I Pass, MD, is a Professor of Cardiothoracic Surgery and
cells to transform and progress into malignant mesothelioma.
16
Based on these
Surgery and Division Chief for Thoracic Surgery and Thoracic findings, high-risk cohorts in Turkey will be treated with ranpirnase, a
Oncology at New York University (NYU) School of Medicine. He is
ribonuclease (RNase) that inhibits NF-κB activation, which will hopefully block
internationally recognized as an expert in the multidisciplinary
management of lung cancer, mesothelioma, and esophageal
this pathway and help prevent the development of MPM.
cancer, and the management of pulmonary metastases. Dr Pass has
co-authored over 300 original reports and edited various editions
Considerable controversy regarding the role of simian virus 40 (SV40) in the
of oncological publications. He has received the National Institutes
of Health (NIH) Directors’ Award, the President’s Award for Clinical
pathogenesis of MPM persists today. SV40 is a rhesus monkey DNA virus,
Research at Karmanos Cancer Institute, and the Wagner Medal likely introduced to humans from contaminated Salk polio vaccines
from the International Mesothelioma Interest Group.
produced between 1955 and 1978.
17
SV40 has been associated with the
E: harvey.pass@nyumc.org development of MPM in humans and animal models.
18,19
Overall, the role of
SV40 in MPM is a controversial topic.
60 © TOUCH BRIEFINGS 2008