Article Date: 28 June 2006
Corporation (Nasdaq: ACEL) announced today that groundbreaking, independent new research findings show that the elusive molecular mechanism that asbestos uses to provoke lung cancer may have been identified. The research also found that ONCONASE(R) (ranpirnase) may be one of the most effective methods of treatment for mesothelioma and lung cancer caused by this mechanism, and may even reduce the incidence of these cancers in those exposed to asbestos.
These findings were included in the article, 'TNF-Alpha inhibits asbestos induced cytotoxicity via a NF-KappaB dependent pathway, a possible mechanism for asbestos induced oncogenesis,' published in the June 23rd issue of Proceedings of the National Academy of Sciences (PNAS), the official journal of the U.S. National Academy of Sciences. Michele Carbone, M.D., Ph.D., authored the article with Dr. Haining Yang from the Thoracic Oncology Program, Cardinal Bernardin Cancer Center, Loyola University, Chicago, and 10 other leading U.S. cancer researchers. Dr. Carbone is Professor and Director, Thoracic Oncology Cancer Center, University of Hawaii, and serves as Chairman of Alfacell's Thoracic Cancer Advisory Board.
Dr. Carbone and his colleagues found that asbestos triggers the release of TNF-Alpha (Tumor Necrosis Factor-Alpha), a pro-inflammatory cytokine critical to the functioning of both innate and adaptive immune responses. The release of TNF-Alpha sets in motion a biochemical chain of events that led to the protection of asbestos-damaged cells from death. The cells exposed to asbestos were found to have produced TNF-Alpha. This caused the activation of the NF-KappaB (Nuclear Factor-Kappa B) protein, a transcription factor, found in all cell types, that plays a critical role in regulating immune response. Ineffective regulation of NF-KappaB has been linked to cancer and other diseases. The activation of NF-KappaB protected asbestos-damaged cells against cell death. Because the damaged cells did not die, they could then go on to develop into a cancer.
The authors state that because of this novel understanding of the molecules and mechanisms involved in asbestos toxicity, new methods of prevention and treatment could be developed that specifically target the inflammatory pathway activated by TNF-Alpha and its target NF-KappaB. ONCONASE was one of only two drugs cited in the article as targeting these pathways. As such, the researchers concluded that ONCONASE holds promise to reduce the incidence of mesothelioma and lung cancer in asbestos-exposed cohorts (groups of patients).
"ONCONASE inhibits the same pathways that we have shown lead to mesothelial cell malignant transformation and mesothelioma. Therefore, we hope to test the possible efficacy of this drug to prevent mesothelioma in high risk cohorts. The minimal side effects of ONCONASE make this approach feasible," stated Dr. Carbone.
Zbigniew Darzynkiewicz, M.D., Ph.D., Director of the Brander Cancer Research Institute, New York Medical College and a member of Alfacell's Scientific Advisory Board, stated, "The mechanism by which ONCONASE produces these effects appears to involve suppression of induction of the survival genes triggered by anti-tumor agents in cancer cells. Indeed, in preclinical studies, ONCONASE was found to amplify the efficacy of several chemotherapy drugs."
Dr. Darzynkiewicz added, "Many other types of cancer utilize the same pathway as mesothelioma. As such, it is reasonable to expect that ONCONASE will have wide clinical application as an anti-cancer agent, with particular promise as an adjunct in chemotherapy or in radiotherapy in treatment regimens for many different tumor types."
"Eight years ago, we hypothesized on the role of TNF-Alpha and NF-KappaB in ONCONASE's mechanism of action (Deptala et al, International Journal of Oncology, July 1998; Potentiation of tumor necrosis factor induced apoptosis by ONCONASE)," Dr. Darzynkiewicz concluded. "It is exciting to see strong affirmation of that hypothesis today."
Alfacell Corporation is a biopharmaceutical company focused on the discovery, development and commercialization of novel therapeutics for cancer, using its proprietary ribonuclease (RNase) technology platform. ONCONASE(R) (ranpirnase), Alfacell's lead investigational drug candidate, is currently being evaluated in several studies, including a Phase IIIb trial for malignant mesothelioma (MM) and a Phase I / II trial in Non-Small Cell Lung Cancer (NSCLC). For more information, please visit http://www.alfacell.com.
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Source: Medical News Today