MLNM,
Study Validates That Melastatin(TM) Gene Assists With Prognosis Of Melanoma
--Findings Published in Journal of Clinical Oncology--
CAMBRIDGE, Mass., Jan 12, 2001 /PRNewswire via COMTEX/ -- Millennium Pharmaceuticals, Inc. (Nasdaq: MLNM chart, msgs), and investigators from Massachusetts General Hospital have issued data that further validate that the expression of Melastatin(TM) helps to determine the risk of metastatic cutaneous melanoma-or skin cancer-in a study in the January 15, 2001, Journal of Clinical Oncology (JCO). The activity of the Melastatin(TM) gene in cutaneous melanoma tumors accurately predicts which patients are at most risk of having their skin cancer metastasize, and those most likely to remain disease free, based on findings in the study.
( Photo:http://www.newscom.com/cgi-bin/prnh/19991220/MLNMLOGO )
In the study published in JCO, entitled "Melastatin Expression and Prognosis in Cutaneous Malignant Melanoma," the investigators found patients in whom the Melastatin(TM) gene is active or expressed were more likely to survive, as defined by an eight-year disease-free period, than patients whose tumors showed down regulation of Melastatin(TM) gene expression (p<0.0001). The study examined melanomas from 150 patients diagnosed between 1988 and 1994 using the American Joint Committee on Cancer (AJCC) system for classifying stage I and II disease.
Disease-free survival is influenced independently by Melastatin(TM) gene expression, cell division as measured by mitotic rate, and tumor thickness, according to the study findings. The loss of Melastatin(TM) gene expression increased the risk of cancer metastasis over time six-fold, the investigators found, when controlling for mitotic rate and tumor thickness.
The rate for disease-free eight-year survival was 100 percent for the stage I patients who expressed the Melastatin(TM) gene, which was 57 percent (n = 33) of all stage I patients included in the study. In comparison, the remaining 43 percent (n = 25) of stage I patients whose tumors showed loss of the gene had a 77 percent rate of eight-year disease-free survival.
Among stage II patients in the study, the rate for disease-free eight-year survival was 90 percent for those with Melastatin(TM) gene expression, which comprised 23 percent (n = 21) of the stage II patients. In contrast, the remaining 77 percent (n = 71) of stage II patients who showed loss of the Melastatin(TM) gene had an eight-year disease-free survival of just 51 percent.
"Our Melastatin(TM) gene research suggests that by examining the biology of cancer via gene expression, rather than a tumor's thickness, clinicians may have an additional data point in determining the prognosis of patients with primary cutaneous melanoma tumors, the most deadly skin cancer," said Michael Kauffman, M.D., Ph.D., vice president of Medicine at Millennium and co-author of the paper. "With the publication of this study, we have proof-of-principle that molecular targets can be used for diagnostic tests in skin cancer."
"By considering the results of Melastatin(TM) gene status along with tumor thickness, physicians may more accurately and cost-effectively target the use of lymph node biopsies and adjuvant therapies in patients with localized melanoma," said Lyn M. Duncan, M.D., associate professor of pathology at Massachusetts General Hospital and Harvard Medical School, and lead author of the paper.
Skin Cancer-Cutaneous Melanoma
According to the American Cancer Society (ACS), cancer of the skin is the most common of all cancers. Melanoma accounts for about 4 percent of skin cancer cases, but causes about 79 percent of skin cancer deaths.
Melastatin(TM) Research
When active or expressed, the gene for Melastatin makes messenger RNA (mRNA), which is needed to make proteins. In previous studies, investigators noted that the gene produced mRNA in inactive cutaneous melanoma cells, but in highly aggressive melanoma cells, the gene was essentially inactive.
In a study published in the November 2000 Human Pathology, Massachusetts General Hospital and Millennium investigators noted that Melastatin(TM) gene expression correlated with cutaneous melanoma tumor progression, thickness and the potential for metastasis in normal skin, benign melanocytic nevi (moles), primary cutaneous melanoma and melanoma metastases. For the study published in JCO, the investigators correlated disease-free status with measures of the mRNA in the patients' primary cutaneous melanoma.
Melastatin(TM) Commercialization
In March 2000, Millennium received a key United States patent relating to the Melastatin(TM) gene and metastatic melanoma. The award, issued as U.S. Patent No. 6,025,137, covers methods of detecting Melastatin(TM) in patient tissue samples in order to determine whether a patient has, or is at risk for developing, metastatic melanoma.
Metastatin(TM) was the first gene delivered by Millennium to Becton Dickinson under the five-year strategic alliance which the two companies established in February 1999 for the development of Diagnomic(TM) products. The alliance focuses on several areas of oncology including melanoma, cervical, breast, ovarian, uterine and prostate. Diagnomics(TM) are molecular diagnostic tests that describe a patient's current medical condition and provide prognostic and therapeutic information. Becton Dickinson has exclusive rights to Diagnomic(TM) products in each of these areas.
Millennium, a leading biopharmaceutical company, applies its comprehensive and integrated science and technology platform for the discovery and development of breakthrough therapeutic and predictive medicine products, with a goal of delivering personalized medicine. Through the industrialization of this gene-to-patient platform, Millennium is also striving to accelerate the process of drug discovery and development. Headquartered in Cambridge, Mass., Millennium currently employs more than 1,200 people.
This press release contains "forward-looking statements," including Millennium's expectations of future industry conditions, strategic plans and forecasts of operational results. Various risks may cause Millennium's actual results to differ materially, including: uncertainties about its drug discovery and clinical development processes, uncertainties about obtaining patent protection for its discoveries and about the commercial limitations imposed by patents owned or controlled by third parties; Millennium's dependence upon strategic alliance partners to develop and commercialize products and services based on its work; uncertainties about obtaining regulatory approvals to market products and services resulting from its development efforts; and the requirement for substantial funding to conduct research and development and to expand commercialization activities. For a further list and description of such risks and uncertainties, see the reports filed by Millennium with the Securities and Exchange Commission. Millennium disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.
Editor's Note: This release is available on Millennium's Web site at: www.millennium.com
Source: Millennium Pharmaceuticals, Inc. |
