PHLBI Medical Research
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| Dr. Robert Cameron with Dr. Dongmei Hou |
Mesothelioma Research Under the Direction of Dr. Robert Cameron
Dr. Robert Cameron is committed to making the Pacific Heart, Lung & Blood Institute a worldwide leader in researching mesothelioma, a rare asbestos-related cancer that is uniformly fatal and in dire need of novel diagnostic, screening, staging, and treatment approaches. Dr. Cameron has been at the forefront of developing innovative therapies for extending the lives of mesothelioma patients. Dr. Cameron’s research plan for PHLBI includes programs involving Immunotherapy, and Screening/Early Detection/Prevention
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Immunotherapy. There is significant data and experience which indicates that mesothelioma may be successfully treated with manipulation of the immune system. Reports in the medical literature reveal success using immunotoxins and interferon. PHLBI plans to aggressively pursue the use of immune stimulating factors in the treatment of mesothelioma.
Immunotoxin Immunotherapy Projects. Recent preliminary data indicates that a specific immunotoxin (interleukin-4 or “IL-4”) has potent anti-cancer activity specifically in mesothelioma. PHLBI plans to explore combinations of the toxin with other treatments including chemotherapy, hyperthermia, and interferon therapy. This will be carried out in the laboratory using cells grown in culture. The ultimate goal is to apply this promising therapy in human patients in a clinical trial. This would require making enough of the toxin in a strict FDA-approved manner. Yet, if the findings in animal work are borne out by human administration, this toxin could be a key to significant progress toward a cure for this dreaded disease.
Project #1: Immunotoxin combinations in vitro. This project will explore treatment combinations such as IL-4 immunotoxin with chemotherapy, hyperthermia, and interferon therapy conducted in the “Punch” Worthington Research Laboratory with mesothelioma cells grown in culture. The results of this project will guide further research to be conducted in animals (see Project #2 below).
Project #2: Immunotoxin combinations in vivo. This project will explore treatment combinations such as IL-4 immunotoxin with chemotherapy, hyperthermia, and interferon therapy conducted in the “Punch” Worthington Research Laboratory with mesothelioma cells injected into animals (mice). The results of this project will be used to guide further research to be conducted in humans.
Project #3: Immunotoxin combinations in human clinical trials. This project will explore treatment combinations such as IL-4 immunotoxin with chemotherapy, hyperthermia, and interferon therapy conducted at UCLA and other mesothelioma treatment centers across the country.
Interferon Immunotherapy Projects. Interferon alpha has shown promising results in preliminary studies at UCLA and other clinical trials. The reasons are not clear but may involve a direct inhibitory effect on tumor cells, stimulation of the immune system and inhibition of blood vessel formation (angiogenesis). Interferons are normal messenger proteins that humans produce in response to viral infections and other specific infections such as tuberculosis. It is believed that they are also vital to the body’s ability to fight abnormal cells like cancer cells. PHLBI plans to explore the use of interferons in the treatment of mesothelioma in both basic science experimentation and human clinical trials.
Project #1: Interferon combinations in vitro. This project will explore the use of interferon with hyperthermia and other immune stimulating cytokines in the treatment of mesothelioma cells in culture. These experiments will be conducted in the “Punch” Worthington Research Laboratory and the results will be used to guide further research to be conducted in animals (see Project #2 below).
Project #2: Interferon combinations in vivo. This project will explore the use of interferon with hyperthermia and other immune stimulating cytokines in the treatment of mesothelioma cells in animals (mice). These studies will be conducted in the “Punch” Worthington Research Laboratory and the results will be used to guide human clinical (see Project #3 below).
Project #3: Interferon in combination with interleukin-2 and/or other cytokines as defined by Projects #1 and #2 above used to plan human clinical trials with interferon possibly with interleukin-2 priming prior to surgical removal of the tumor. This will be conducted at UCLA and other mesothelioma treatment centers across the country.
Project #4: COX-2 inhibitors (Celebrex, etc.) in combination with interferon maintenance therapy and/or other cytokines as defined by Projects #1 and #2 above used to plan human clinical trials with COX-2 inhibitors with or without interferon as maintenance therapy following standard therapy. This will be conducted at UCLA and other mesothelioma treatment centers across the country.
Project #5: Angiogenesis inhibition. Numerous agents have been tested with and without chemotherapy for the treatment of mesothelioma and other cancers by inhibition of new blood vessel formation. This will be explored in the seldom-tested setting of chronic maintenance and may also be combined with interferon and COX-2 inhibition therapy. This project will be conducted at UCLA and other mesothelioma treatment centers across the country.
Screening/Early Detection/Prevention. Populations of people exposed to asbestos, and therefore at risk for mesothelioma and lung cancer, currently have no way of determining whether they will develop one of these terrible cancers. Only approximately 15% of patients exposed to asbestos will actually develop mesothelioma or lung cancer. In addition, there is no test which can detect mesothelioma at an early or even pre-malignant stage. In order to help people at risk detect the disease at an early stage when there are many more options available for effective treatment, PHLBI plans an aggressive program for improving screening, early detection and prevention.
Screening Projects. Breath test for volatile hydrocarbons. In order for persons exposed to asbestos to determine whether they are among the smaller population of those who are at high risk of actually developing asbestos-related malignancies, PHLBI plans to examine the volatile hydrocarbons which are exhaled in people’s breath (breath testing). Dr. Cameron has already gained significant experience in breath testing of patients with lung cancer and is eager to expand the testing to patients exposed to asbestos and at risk for mesothelioma. The test involves breathing into a tube which collects volatile hydrocarbons on a filter so they can be analyzed. This project will be conducted at UCLA and other mesothelioma treatment centers across the country.
Early Detection Projects. Proteonomics in early detection of mesothelioma. Normal and abnormal cells in the body generate distinctive amounts and kinds of proteins. This “protein profile” can be used much like a fingerprint. PHLBI plans to conduct investigation to determine the “protein profile” generated by mesothelioma cells so that simple blood tests can be used to detect mesothelioma at an early stage. This project will involve analysis of blood and urine from mesothelioma victims at all stages of disease as well as normal and asbestos-exposed people to better define protein profiles in these populations. This project will be conducted at UCLA and other mesothelioma treatment centers across the country.
Prevention Projects. COX-2 inhibition as prevention of mesothelioma. Chronic inflammation induced by asbestos fibers has been implicated in the development of mesothelioma. One way to prevent the development of mesothelioma in patients with known significant asbestos exposure is to treat them with COX-2 inhibitors (Celebrex, etc.) of inflammation. This has already been shown to prevent other cancers, such as colon cancer, and may be effective in lung cancer. This project will be conducted at UCLA and other mesothelioma treatment centers across the country in conjunction with Unions of high risk workers/patients.
Administrative Improvements in Medical Care
In addition to research into therapeutic and scientific advancements, Dr. Cameron is committed to investigating ways in which the administration of medical care can be improved so that patients are vested with additional knowledge, security and control regarding their treatment.
Electronic Medical Records System. Dr. Cameron believes in empowering patients with their own medical records for better understanding and control over their own health and treatment. Dr. Cameron and PHLBI support an electronic medical records system which is directly accessible to patients. Such a system would enable data to be directly entered from point of generation and allow for the coordinated transfer of medical information among providers and research studies. This type of system would result in complete and organized records possessed by all persons and facilities involved in the treatment, thereby increasing the time for meaningful discussions of medical problems between health care providers and patients and improving the quality and efficacy of patient care.
Health Care Systems. Dr. Cameron recognizes the need for development of novel methods of health care delivery. Dr. Cameron and PHLBI support a system founded on a “ability to pay” basis. This means that instead of every person paying a health-handicapped insurance premium to a “for-profit” company, people would pay based on their ability to contribute to a “catastrophic” government fund while using individual savings accounts for lower cost items. This would allow individual provider-based pricing but income-based premium payments. This project will involve collection and analysis of data on individual access and consistency of access system approaches.