A polyomavirus known as MCPyV is associated with clinical outcomes, including fewer metastases and better survival, in patients with a rare form of skin cancer called Merkel cell carcinoma, according to a new study published online June 17 in the JNCI.

Integration of the Merkel cell carcinoma polyomavirus (MCPyV) genome into the tumor genome was recently found to be frequent in skin cancers, but the clinical consequences of MVPyV genomic integration was unclear.

To examine the consequences of viral DNA integration, Heikki Joensuu, M.D., of the Department of Oncology at Helsinki University Central Hospital, and colleagues, conducted histopathologic and molecular biological analyses of tumor tissue and DNA from 109 Finnish patients who were diagnosed with Merkel cell carcinoma from 1979 to 2004.

Approximately 50% of the tumors were positive for MCPyV DNA. These cancers tended to be located in a limb, to have less frequent nodal or distant metastases at the time of diagnosis, and to be associated with better survival compared with MCPyV DNA-negative cancers.

“Identification of MCPyV as a contributing factor to the pathogenesis of Merkel cell carcinoma might provide novel choices for future therapeutic strategies,” the authors write.

In an accompanying editorial, James A. DeCaprio, M.D., of the Dana-Farber Cancer Institute in Boston, points out parallels between MCPyV infection in Merkel cell carcinoma and human papillomavirus infection in head and neck cancers, suggesting reasons that the presence of these viruses would predict a better prognosis.

“Perhaps expression of the viral oncogenes can induce or promote the development of cancers that have fewer host cell chromosomal abnormalities, which may result in tumors with simpler genomic abnormalities,” the editorialist writes. “Alternatively, the viral oncogenes may specifically perturb host signaling pathways, including immune surveillance, that render them less aggressive or lethal.”

Author:
Joensuu Heikki

Source:
Steve Graff
Journal of the National Cancer Institute

CytRx Corporation (NASDAQ:CYTR), a biopharmaceutical research and development company engaged in the development of high-value human therapeutics, announced that tamibarotene, currently under evaluation in a U.S. registration trial as a third-line treatment for acute promyelocytic leukemia (APL), showed statistically significant anti-tumor activity in human myeloma cells transplanted into animals. Multiple myeloma is an incurable malignant tumor of the plasma cells of bone marrow. Results of the trial were published in the June 2009 peer-reviewed journal Cancer Science (Volume 100, No. 6, Pages 1137-1143).

“These results support our contention that tamibarotene’s mechanism of action may provide broad commercial potential as a therapeutic treatment beyond APL to other cancers such as multiple myeloma,” said Steven A. Kriegsman, CytRx President and CEO. “Despite advances in therapies that improve the quality of life and length of survival, many multiple myeloma patients experience severe side effects from current therapies, prompting the need for additional therapies.”

“We are evaluating opportunities for a Phase 2 clinical program with tamibarotene as a multiple myeloma therapy, as well as investigating partnership prospects for developing and commercializing tamibarotene in the U.S. for both multiple myeloma and APL,” he added.

CytRx has the right to develop tamibarotene as a treatment for multiple myeloma in Europe, and has the option to expand its license for the use of tamibarotene for multiple myeloma and certain other oncology applications in the U.S. Tamibarotene is currently approved for relapsed or refractory treatment of APL in Japan.

The animal trial, conducted by an independent third party in Japan, was designed to evaluate the activity of tamibarotene as a multiple myeloma treatment alone and in combination with a glucocorticoid, a commonly prescribed treatment for this disease. Five different human myeloma cell lines were treated with tamibarotene alone, glucocorticoids alone, or tamibarotene + glucocorticoids in cell culture. Tamibarotene by itself inhibited the growth of these tumor cells two- to 10-fold more potently than all-trans retinoic acid (ATRA), a less specific relative of tamibarotene which has previously been shown to inhibit the growth of human myeloma cells. Importantly, the combination of tamibarotene with glucocorticoids was found to show markedly greater growth inhibition than either drug alone.

Human myeloma cells were then transplanted into mice with compromised immune systems to study the tumor growth-inhibitory effects of these drugs. Both tamibarotene and glucocorticoids by themselves reduced the rate of tumor growth. However, the combination of tamibarotene with glucocorticoids showed a synergistic interaction that resulted in markedly decreased tumor growth and increased survival compared with either drug alone. Trial investigators concluded that tamibarotene in this drug combination approach was among the most promising potential therapeutic regimens for multiple myeloma, especially in high-risk patients, and should be further investigated.

“Our drug tamibarotene is more stable and may have fewer adverse events than ATRA, with both drugs demonstrating the ability to force certain types of leukemia cells to cease growing uncontrollably and return to performing their normal functions - a process known as terminal differentiation,” said Jack Barber Ph.D., CytRx’s Chief Scientific Officer. “Multiple myeloma cells are thought to grow uncontrollably due in part to a growth factor called IL-6. Glucocorticoids are a potent inducer of cell death; however this benefit may be offset by their known activation of IL-6 activity. Tamibarotene has previously shown the ability to interfere with the normal functioning of IL-6, which could be the foundation for the anti-proliferative effects of tamibarotene in multiple myeloma, particularly in combination with glucocorticoids.

“We are delighted and encouraged by this proof of concept, which could ultimately increase the potential market for tamibarotene,” added Dr. Barber.

About Multiple Myeloma

Multiple myeloma is the second most common hematologic malignancy in the U.S. According the National Cancer Institute, an estimated 20,580 new cases of multiple myeloma will be diagnosed in the U.S., and 10,580 multiple myeloma patient deaths will be recorded in 2009. According to industry leading researcher Mattson Jack Group, currently in the top seven markets (including the U.S., EU and Japan), the number of new cases each year is expected to total more than 43,500. The average five-year survival is 35 percent and the American Cancer Society found multiple myeloma to be the sixth deadliest cancer in terms of a mortality-to-incidence ratio.

Multiple myeloma is characterized by malignant plasma cells that form tumors in the bone marrow. These plasma cell tumors can spread throughout the bone marrow, thereby disrupting the production of red blood cells and platelets, which normally occur in the bone marrow. Excessive amounts of malignant plasma cells also may decrease the number of white blood cells, which are important in fighting off infections.

About Tamibarotene

Tamibarotene is an orally available, rationally designed, synthetic retinoid compound designed to potentially avoid toxic side effects by binding to its molecular target more selectively than all trans-retinoic acid (ATRA), the current first-line treatment for APL. A Special Protocol Assessment (SPA) is in place with the U.S. Food and Drug Administration (FDA) for a Phase 2 registration clinical trial, known as STAR-1, which is evaluating the efficacy and safety of tamibarotene as a third-line treatment for APL. The STAR-1 trial is ongoing and currently includes 30 clinical sites, 22 of which are in Europe, and one in Canada. CytRx believes that successful data from the STAR-1 trial and supporting studies, in conjunction with data from the Japanese clinical trials, will form the basis for a New Drug Application (NDA).

The FDA has granted Orphan Drug Designation and Fast Track Designation for the use of tamibarotene in patients with relapsed or refractory APL following treatment with all-trans retinoic acid (ATRA) and arsenic trioxide. The efficacy of orally administered tamibarotene was demonstrated in two Phase 2 studies conducted in Japan in a total of 63 Japanese subjects with APL. The overall complete response rate in these subjects was 60%. In subjects experiencing their first relapse, the overall complete response rate was 81%. In addition to multiple myeloma, CytRx also retains an option to expand its licenses for the use of tamibarotene in other fields in oncology, including myelodysplastic syndrome and certain solid tumors in the U.S., and myelodysplastic syndromes and solid tumors other than hepatocellular carcinoma in Europe.

Source
CytRx Corporation

Accuray Incorporated (Nasdaq: ARAY), a global leader in the field of radiosurgery, announced that the Turkish Ministry of Health has purchased two CyberKnife(R) Robotic Radiosurgery Systems for installation in Ankara and Istanbul, Turkey.

Turkey’s first CyberKnife System was installed at Anadolu Medical Center in January 2005. A second system was installed in Turkey at Hacettepe University Hospital in May 2007. In addition to the two recent purchases by the Ministry of Health, a fifth System for installation within Turkey was recently purchased by Istanbul University, Oncology Institute, a leading academic institution in Capa district, Istanbul. The sales of these Systems were coordinated by local distributor Radontek Ltd.

“The Turkish Ministry of Health’s purchase of two CyberKnife Systems is further validation of the System’s worldwide clinical acceptance, particularly amongst government institutions,” said Euan S. Thomson, Ph.D., president and CEO of Accuray Incorporated. “Full body radiosurgery with the CyberKnife System has truly established itself as a viable treatment alternative for cancer patients around the world.”

The CyberKnife Systems for Ankara and Instanbul were purchased by the Turkish Ministry of Health for Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi (Ankara) and Dr. Lutfu Kirdar Kartal Egitim ve Arastirma Hastanesi (Istanbul).

About the CyberKnife(R) Robotic Radiosurgery System

The CyberKnife Robotic Radiosurgery System is the world’s only robotic radiosurgery system designed to treat tumors anywhere in the body non-invasively. Using continual image guidance technology and computer controlled robotic mobility, the CyberKnife System automatically tracks, detects and corrects for tumor and patient movement in real-time throughout the treatment. This enables the CyberKnife System to deliver high-dose radiation with pinpoint precision, which minimizes damage to surrounding healthy tissue and eliminates the need for invasive head or body stabilization frames.

About Accuray

Accuray Incorporated (Nasdaq: ARAY), based in Sunnyvale, Calif., is a global leader in the field of radiosurgery dedicated to providing an improved quality of life and a non-surgical treatment option for those diagnosed with cancer. Accuray develops and markets the CyberKnife Robotic Radiosurgery System, which extends the benefits of radiosurgery to include extracranial tumors, including those in the spine, lung, prostate, liver and pancreas. To date, the CyberKnife System has been used to treat more than 60,000 patients worldwide and currently more than 164 systems have been installed in leading hospitals in the Americas, Europe and Asia.

Safe Harbor Statement

The foregoing may contain certain forward-looking statements that involve risks and uncertainties, including uncertainties associated with the medical device industry. Except for the historical information contained herein, the matters set forth in this press release, including statements relating to commercialization of products, clinical studies, and regulatory review and approval are forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements speak only as of the date the statements are made and are based on information available at the time those statements are made and/or management’s good faith belief as of that time with respect to future events. You should not put undue reliance on any forward-looking statements. Important factors that could cause actual performance and results to differ materially from the forward-looking statements we make include: market acceptance of products; competing products, the combination of our products with complementary technology; and other risks detailed from time to time under the heading “Risk Factors” in our report on Form 10-K for the 2008 fiscal year, as updated in our Form 10-Q filed on May 6, 2009 and our other filings with the Securities and Exchange Commission. The Company’s actual results of operations may differ significantly from those contemplated by such forward-looking statements as a result of these and other factors. We assume no obligation to update forward-looking statements to reflect actual performance or results, changes in assumptions or changes in other factors affecting forward-looking information, except to the extent required by applicable securities laws.

Source: Accuray Incorporated