December 2009

Research Corner

An ESUN Resource

A REQUEST TO THE NATIONAL CANCER INSTITUTE FROM THE SARCOMA RARE CANCER COMMUNITY

November 19, 2009

John Niederhuber, M.D.
Director, National Cancer Institute
Building 31, Room 10A24
9000 Rockville Pike
Bethesda, MD  20892

Subj:  EXPANSION OF NCI CANCER GENOME ATLAS PROJECT TO INCLUDE SARCOMA

Dear Dr. Niederhuber:

The undersigned represent cancer patients and their families, health care providers, as well as patient advocacy, patient support and scientific research organizations interested in and affected by rare cancers known as "sarcoma."

As you know, in President Obama's first "Address to Congress" he announced the bold goal of curing cancer in our lifetimes.  Regarding our community, the President specifically addressed the needs of people with rare cancers in the 2008 Obama/Biden Plan to Combat Cancer. We are sure you would agree that sarcoma certainly qualifies for this distinction. 

Recently, we noted the visit that President Obama made to the NIH to highlight the increased funding that his administration had made available to the NCI to accelerate progress against cancer.  Subsequent to the gathering, it was announced that specific new funds were to be aimed at the NCI Cancer Genome Atlas Project (TCGA), and that upwards of twenty new cancer types would be added to TCGA.

We would like to take this opportunity to encourage you to consider the following information regarding sarcoma as you decide the specific cancer types to be added to the project:

1) Unlike several cancer types, sarcoma is prevalent in all ages of the U.S. population, and is especially prevalent in children. Thus each child saved from death by sarcoma adds 60-70 years of value and contribution to society.

2) There are very limited treatment options for sarcoma, with the sole FDA approved agent being approved over 20 years ago.

3) Though sarcoma is an uncommon cancer, research discoveries in sarcoma have been shown to go on and provide enormous insight into more prevalent tumors. For example, work to elucidate the role of the P53 gene played in explaining heritable cancers, prediction of the RB gene leading to the multiple "hit" hypothesis in carcinogenesis, research of the src gene leading to the viral genetic relationship with cancer, and the more recent work of the importance of the ews fusion gene in prostate cancer, all have their origin in research based in studying sarcomas.  Thus there would be a synergistic efficiency to data obtained by uncovering genomic abnormalities in sarcomas as a result of being a part of TCGA.

4) The sarcoma community, including academic centers and patient advocacy groups, is an extraordinarily tight knit, engaged and cooperative community. We appreciate that one of the key elements driving the tumor choices is the availability of large numbers of frozen tumors with matched normal blood or tissue, either prospective or retrospective, obtained with proper consents. As a result of our community's unity, it can be anticipated that participation in an endeavor such as TCGA would result in rapid and robust collection of high quality tissue samples and completion of other requirements of participation in the program.

The rare cancer community, and specifically the sarcoma community, has been energized by the recent increases in funding allocated to the NCI.  We hope that by addressing the needs of this relatively neglected group of cancer patients, we will accomplish the original intent of President Obama's concern for patients with rare cancers.

If we may be of assistance, please do not hesitate to call upon our union of organizations as a resource.  Thank you again for your diligent work on behalf of cancer patients.

Sincerely,

Sarcoma Alliance for Research Consortium BeatSarcoma
Connective Tissue Cancer Network Connective Tissue Oncology Society
Desmoid Tumor Research Foundation  Ewings Sarcoma Alliance
Foster Foundation  GIST Cancer Research Fund  
GIST Support International   Hope Fund for Sarcoma Research
Kristen Ann Carr Fund Liddy Shriver Sarcoma Initiative
Life Raft Group National Leiomyosarcoma Foundation
Northwest Sarcoma Foundation Polish Sarcoma Patient Advocacy
Sarcoma Alliance Sarcoma Foundation of America
The Alliance Against ASP Sarcoma The sPECial Fund
The Swing Away Foundation WWWW Foundation, Inc. (QuadW)

 

The Claudia Cohen Research Foundation Announces Annual Prize for Outstanding Gynecologic Cancer Researcher

The Claudia Cohen Research Foundation in association with the Gynecologic Cancer Foundation (GCF) announced today that it will award an annual $50,000 prize to an individual in recognition of his or her outstanding contributions to research improving the care of women with gynecologic cancer. The awardees will have made important contributions that improve gynecologic cancer patient care, including early detection. The award will be made to the individual rather than his/her institution. The prize named is being funded by the Claudia Cohen Research Foundation (CCRF) in honor of Claudia Cohen who lost her battle with uterine leiomyosarcoma in 2007. Ms. Cohen was a highly respected journalist and philanthropist. Individuals can apply for this prize or nominators can propose potential candidates by filling out the application form which is downloadable on the GCF Web site. The deadline for applications is January 8, 2010. The GCF Award's Committee will select the awardee with the first prize to be announced at the 2010 SGO Annual Meeting on Women's Cancer in San Francisco, California. The Claudia Cohen Research Foundation was founded by Ms. Cohen's daughter, Samantha, and her sisters Caleigh and Debra Perelman, to foster research aimed at reducing the burden of gynecologic cancer.

 

Prognostic factors in pulmonary metastasized high-grade osteosarcoma

The resection of pulmonary metastases has previously been reported to improve outcome in high-grade osteosarcoma (OS) patients. This study sought to validate these results.  In the study there were 88 OS patients with pulmonary metastases either at diagnosis or during follow-up.  All were treated at Leiden University Medical Center between January 1, 1990 and January 1, 2008.  All were under the age of 40; there were 79 conventional cases, 8 cases of telangiectatic and 1 case of small cell OS. The results were as follows: In total, 56 of 88 patients with pulmonary metastases were treated by metastasectomy. Resectability of pulmonary metastases was the main prognostic factor. In patients with primary non-metastatic OS, a longer relapse free interval to pulmonary metastases was significantly associated with better survival (P = 0.02). Independent risk factors determining worse survival after metastasectomy in multivariate analysis were male sex (P = 0.05), higher number of pulmonary nodules (P = 0.03), and non-necrotic metastases (P = 0.04). Whether surgery for recurrent pulmonary metastases was performed did not influence survival. Histological subtype of the primary tumor, histological response in the primary tumor after neo-adjuvant chemotherapy, occurrence of local relapse, local resection or amputation of the primary tumor and age at diagnosis did not influence outcome. The investigators conclude: This cohort of patients with detailed follow-up data enabled identification of important risk factors determining survival in OS patients with pulmonary metastases. They demonstrate that after repeated metastasectomies, a subset of patients can be cured.

 

Noninvasive Imaging Surrogate of Angiogenesis in Osteosarcoma

Measurement of tumor angiogenesis by qualitative analysis of dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI), and its association with diffusion-weighted (DW)-MRI and glucose metabolism using positron emission tomography-computerized tomography (PET-CT) scan has not been explored in osteosarcoma. This study was aimed to evaluate the potential of these surrogates. Thirty-one treatment naive patients with osteosarcoma underwent MRI and PET-CT preceding and following three cycles of neoadjuvant chemotherapy (NACT) and surgery. Time intensity curves (TICs) representing low microvascular permeability is persistent type while that of high permeability are plateau and washout types. Vascular endothelial growth factor (VEGF) expression was assessed in biopsy and resected specimens by immunohistochemistry. The sample was considered VEGF positive when intensive positive staining of VEGF was observed in >10% of the tumor cells in biopsy or resection specimens. The results were as follows: TIC could correctly identify all 28 VEGF positive samples at baseline and 24/25 (96%) of VEGF positive samples and 5/6 (83%) of VEGF negative samples after NACT. The change in curve pattern from washout/plateau to persistent type was in agreement with corresponding decrease in microvascular permeability, that is, VEGF expression. For persistent type of TIC, mean change in VEGF was 73.3 ± 43.2% and for plateau and washout type of TIC it was 19.54 ± 45% and 16.66 ± 28.86%, respectively (P  0.04). VEGF expression did not correlate with DW-MRI and PET-CT parameters. The investigators conclude: This study suggests an important role of DCE-MRI as a noninvasive imaging surrogate of tumor angiogenesis in osteosarcoma based on visual inspection of TIC.

 

Deletion of the WWOX gene and frequent loss of its protein expression in human osteosarcoma

The purpose of this study was to evaluate the role of WWOX gene in human osteosarcoma. An array comparative genomic hybridization on 10 frozen osteosarcoma specimens and immunohistochemical staining of 55 formalin-fixed and paraffin-embedded tissues for WWOX was performed. Deletion of the WWOX gene was observed in 3 of 10 samples and the WWOX protein was undetectable in 34 of 55 osteosarcomas. This is the first investigation of the role of WWOX gene in human osteosarcoma. The WWOX gene deletion, loss of its protein expression, and lack of correlation of WWOX expression with patient survival suggest loss of WWOX expression is an early event in the pathogenesis of osteosarcoma and the phenotypic results of its deletion do not imminently result in patient death.

 

Molecular prognosticators of complex karyotype soft tissue sarcoma outcome: a tissue microarray-based study

Molecular markers are currently being utilized as sensitive prognosticators of cancer patient outcome. The investigators of this study sought to identify prognostic biomarkers for complex karyotype soft tissue sarcoma (STS). A large (n = 205) clinically annotated tissue microarray (TMA) was constructed and immunostained for several tumor-related markers. Staining was scored via an automated Ariol image analysis system; data were statistically analyzed to evaluate the correlation of clinicopathological and molecular variables with overall survival (OS) and local recurrence. The results were as follows: Multivariable analysis identified older age [hazard ratio (HR) 1.62, P < 0.0001], nonextremity location (HR 2.95, P = 0.001), high tumor grade (HR 2.5, P = 0.02), and increased matrix metalloproteinase (MMP) 2 expression (HR 1.74, P = 0.04) as predictors for poor OS. Similarly, older age (HR 1.51, P = 0.008), nonextremity location (HR 4.09, P = 0.001), and increased MMP2 expression (HR 6.28, P = 0.006) were all found to correlate with shorter local recurrence-free interval. High nuclear p53 expression was associated with shorter STS local recurrence-free interval, with a trend toward significance. The investigators conclude: Data presented indicate that a clinically annotated TMA can be utilized to identify STS-related prognostic markers. Specifically, MMP2 and nuclear p53 should be further evaluated for their potential inclusion in complex karyotype STS staging systems.

 

Treatment of Relapsed/Refractory Pediatric Sarcomas With Gemcitabine and Docetaxel

This report describes experience with gemcitabine-docetaxel in pediatric patients with relapsed or refractory sarcomas. Ten relapsed/refractory pediatric sarcoma patients including 6 Ewing sarcoma, 2 synovial sarcoma, 1 osteosarcoma, and 1 undifferentiated sarcoma, were treated prospectively, in an outpatient setting, with gemcitabine 1000 mg/m2 over 90 minutes on day 1 and 8, and docetaxel 100 mg/m2 over 2 to 4 hours on day 8 of a 21-day cycle, as an investigational rescue therapy. The results were as follows:  The patients (ages 4 to 18) received a total of 70 cycles of therapy (median 6 cycles; range: 4 to 10 y). All symptomatic patients responded clinically to the new regimen. By Response Evaluation Criteria in Solid Tumors criteria, 4 (40%) patients had a complete response (CR), 1 (10%) had a partial response (PR), 3 (30%) had stable disease (SD), and 2 (20%) had a progressive disease (PD), which provides an objective response rate (CR+PR) of 50%. Median duration of response (CR+PR+SD) was 10 months (range: 6 to 32+ mo). Five out of the 10 patients (50%) are alive, with a median follow-up of 48 months from diagnosis. Mild toxicities (no grades 3 to 4) were encountered and managed in the ambulatory setting. The investigators conclude: The gemcitabine-docetaxel regimen demonstrated antitumor activity against advanced pediatric (mainly Ewing) sarcomas, allowing for good quality of life. Evaluation in a large, formal phase 2 trials for Ewing patients is ongoing.

 

Profiling of high-grade central osteosarcoma and its putative progenitor cells identifies tumourigenic pathways

Osteosarcoma is the most prevalent primary malignant bone tumor in children and young adults, with poor survival in 40% of patients. To identify the signaling pathways involved in tumourigenesis, the investigators of this study compared gene expression in osteosarcoma with that in its presumed normal counterparts. Genome-wide expression profiles were generated from 25 high-grade central osteosarcoma prechemotherapy biopsies, 5 osteoblastomas, 5 mesenchymal stem cell (MSC) populations and these same MSCs differentiated into osteoblasts. Genes that were differentially expressed were analyzed in the context of the pathways in which they function using the GenMAPP programme. The results were as follows:  MSCs, osteoblasts, osteoblastomas and osteosarcomas clustered separately and thousands of differentially expressed genes were identified. The most significantly altered pathways are involved in cell cycle regulation and DNA replication. Several upstream components of the Wnt signaling pathway are downregulated in osteosarcoma. Two genes involved in degradation of -catenin protein, the key effectors of Wnt signaling, Axin and GSK3-, show decreased expression, suggesting that Wnt signaling is no longer under the control of regular signals. Comparing benign osteoblastomas with osteosarcomas identified cell cycle regulation as the most prominently changed pathway. The investigators conclude: These results show that upregulation of the cell cycle and downregulation of Wnt signaling have an important role in osteosarcoma genesis. Gene expression differences between highly malignant osteosarcoma and benign osteoblastoma involve cell cycle regulation.

 

Randomized Trial and Pharmacokinetic Study of Pegfilgrastim versus Filgrastim after Dose-Intensive Chemotherapy in Young Adults and Children with Sarcomas

The purpose of this study was to compare the effectiveness, tolerance, and pharmacokinetics of a single dose of pegfilgrastim to daily filgrastim in children and young adults with sarcomas treated with dose-intensive combination chemotherapy. Patients were randomized to receive a single dose of 100 mcg/kg of pegfilgrastim s.c. or 5 mcg/kg/day of filgrastim s.c., daily until neutrophil recovery after two treatment cycles with vincristine, doxorubicin, and cyclophosphamide (VDC) and two cycles of etoposide and ifosfamide (IE). The duration of severe neutropenia (absolute neutrophil count, ≤500/mcL) during cycles 1 to 4 and cycle duration for all cycles were compared. Pharmacokinetics of pegfilgrastim and filgrastim and CD34+ stem cell mobilization were studied on cycle 1. Growth factor–related toxicity, transfusions, and episodes of fever and neutropenia and infections were collected for cycles 1 to 4. The results were as follows: Thirty-four patients (median age, 20 years; range 3.8-25.8) were enrolled, and 32 completed cycles 1 to 4. The median (range) duration of absolute neutrophil count of <500/mcL was 5.5 (3-8) days for pegfilgrastim and 6 (0-9) days for filgrastim (P = 0.76) after VDC, and 1.5 (0-4) days for pegfilgrastim and 3.75 (0-6.5) days for filgrastim (P = 0.11) after IE. More episodes of febrile neutropenia and documented infections occurred on the filgrastim arm. Serum pegfilgrastim concentrations were highly variable. Pegfilgrastim apparent clearance (11 mL/h/kg) was similar to that reported in adults. The investigators conclude: A single dose per cycle of pegfilgrastim was well tolerated and may be as effective as daily filgrastim based on the duration of severe neutropenia and number of episodes of febrile neutropenia and documented infections after dose-intensive treatment with VDC and IE.

 

Phase I, Pharmacokinetic, and Pharmacodynamic Study of AMG 479, a Fully Human Monoclonal Antibody to Insulin-Like Growth Factor Receptor 1

The purpose of this study was to determine the maximum-tolerated dose (MTD) and to assess the safety, pharmacokinetics, and evidence of antitumor activity of AMG 479, a fully human monoclonal antibody to insulin-like growth factor receptor 1 (IGF-1R). Patients with advanced solid malignancies or non-Hodgkin's lymphoma received escalating doses of AMG 479 intravenously (IV) every 2 weeks (Q2W). Blood samples were assayed to determine pharmacokinetic parameters and IGF-1R occupancy on neutrophils; fluorodeoxyglucose–positron emission tomography scans were used to assess tumor metabolic effects. The results were as follows: Fifty-three patients received 312 infusions of AMG 479 Q2W. Overall, the most common grades 1 to 2 toxicities were fatigue, thrombocytopenia, fever, rash, chills, and anorexia. One dose-limiting toxicity (i.e., grade 3 thrombocytopenia) occurred in a patient at 20 mg/kg during course 1; grade 3 thrombocytopenia (n = 8) and grade 3 transaminitis elevations (n = 1) also were reported but not in the escalation phase. The maximum-planned dose of 20 mg/kg was safely administered; thus, an MTD was not reached. High levels of neutrophil IGF-1R binding and increases from baseline in serum IGF-1 levels were observed in the 12- and 20-mg/kg cohorts. Tumor responses included one durable complete response (CR) and one unconfirmed partial response (PR) in two patients with Ewing/primitive neuroectodermal tumors and included one PR and one minor response in two patients with neuroendocrine tumors. The patients with Ewing/PNET who had a CR have remained disease free on therapy after 28 months. The investigators conclude: AMG 479 can be administered safely at 20 mg/kg IV Q2W. The absence of severe toxicities, attainment of serum concentrations associated with high levels of IGF-1R binding on neutrophils, and provocative antitumor activity warrant additional studies of this agent.

 

Late Recurrence in Pediatric Cancer: A Report From the Childhood Cancer Survivor Study

An increasing percentage of childhood cancer patients are surviving their disease, but there is limited research on late recurrence. The investigators of this study sought to estimate late recurrence rates for the most common pediatric cancers and to determine risk factors for late recurrence. The incidence of late recurrences, or first recurrences that occurred more than 5 years after diagnosis, was analyzed for the most common pediatric cancers using data from the Childhood Cancer Survivor Study, a retrospective cohort of 5-year survivors of childhood and adolescent cancers who were diagnosed between 1970 and 1986. A total of 12,795 survivors with no history of recurrence within 5 years after their original cancer diagnosis were included in the analysis, with a total of 217 127 person-years of follow-up. Cumulative incidence of late recurrence at 5, 10, 15, and 20 years after diagnosis was calculated using death as a competing risk. Adjusted relative rates of late recurrence were obtained using multivariable Poisson regression. All statistical tests were two-sided.  Results were as follows:  Overall, 5-year survivors of pediatric cancers experienced a cumulative incidence of recurrent disease of 4.4%, 5.6%, and 6.2% at 10, 15, and 20 years, respectively. Cumulative incidence varied by diagnosis: Survivors of Ewing sarcoma and astrocytoma had the highest 20-year cumulative incidences at 13.0% (95% confidence interval [CI] = 9.4 to 16.5) and 14.4% (95% CI = 12.3 to 16.6), respectively. In multivariable analysis, the greatest risk factors for late recurrence included diagnosis, combination treatment with chemotherapy and radiation, earlier treatment era, and fewer years since diagnosis (P < .001 for all). The investigators conclude: Late recurrence is a risk for some pediatric cancers. By understanding diagnosis-specific risks, patients, families, and their medical providers can be better informed of the probability of cure.

 

Small interfering RNA library screen of human kinases and phosphatases identifies polo-like kinase 1 as a promising new target for the treatment of pediatric rhabdomyosarcomas

Rhabdomyosarcoma, consisting of alveolar (aRMS) and embryonal (eRMS) subtypes, is the most common type of sarcoma in children. Currently, there are no targeted drug therapies available for rhabdomyosarcoma. In searching for new molecular therapeutic targets, the authors of this paper carried out genome-wide small interfering RNA (siRNA) library screens targeting human phosphatases (n = 206) and kinases (n = 691) initially against an aRMS cell line, RH30. Sixteen phosphatases and 50 kinases were identified based on growth inhibition after 72 hours. Inhibiting polo-like kinase 1 (PLK1) had the most remarkable impact on growth inhibition (∼80%) and apoptosis on all three rhabdomyosarcoma cell lines tested, namely, RH30, CW9019 (aRMS), and RD (eRMS), whereas there was no effect on normal muscle cells. The loss of PLK1 expression and subsequent growth inhibition correlated with decreased p-CDC25C and Cyclin B1. Increased expression of WEE 1 was also noted. The induction of apoptosis after PLK1 silencing was confirmed by increased p-H2AX, propidium iodide uptake, and chromatin condensation, as well as caspase-3 and poly(ADP-ribose) polymerase cleavage. Pediatric Ewing's sarcoma (TC-32), neuroblastoma (IMR32 and KCNR), and glioblastoma (SF188) models were also highly sensitive to PLK1 inhibition. Finally, based on cDNA microarray analyses, PLK1 mRNA was overexpressed (>1.5 fold) in 10 of 10 rhabdomyosarcoma cell lines and in 47% and 51% of primary aRMS (17 of 36 samples) and eRMS (21 of 41 samples) tumors, respectively, compared with normal muscles. Similarly, pediatric Ewing's sarcoma, neuroblastoma, and osteosarcoma tumors expressed high PLK1. The authors conclude: PLK1 could be a promising therapeutic target for the treatment of a wide range of pediatric solid tumors including rhabdomyosarcoma.

 

Current Approach to Pediatric Soft Tissue Sarcomas

This article, authored by Melinda Merchant and Crystal Mackall (Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA), describes the current standard of care for pediatric soft tissue sarcomas.  Pediatric STS are generally defined as those that occur in the first 20 years of life.  The types of sarcomas discussed includes (refer to acronyms list below) RMS, ERMS, ARMS, ESFT, undifferentiated or poorly differentiated sarcomas, DSRCT, SS, MPNST, ASPS and IFS. It also touches on adult-type sarcomas such as liposarcoma, leiomyosarcoma, fibrosarcoma, myxoid chondrosarcoma and clear cell sarcoma.  The following type of information is provided, by tumor type:

The authors emphasis the need for a multidisciplinary approach in treating these sarcomas.  They state, "Radiologists, oncologists, surgeons, and radiation oncologists treating children and young adults with sarcomas ought to be aware of the national and international study options that will provide quality of care and also continue to move the field forward." 

 

Loss Of Tumor Suppressor Gene Essential To Transforming Benign Nerve Tumors Into Malignant Peripheral Nerve Sheath Tumors

Researchers at UCLA's Jonsson Comprehensive Cancer Center have demonstrated that the loss or decreased expression of the tumor suppressor gene PTEN plays a central role in the malignant transformation of benign nerve tumors called neurofibromas into the deadly form of sarcoma know as malignant peripheral nerve sheath tumors. The work, a collaboration between the Institute for Molecular Medicine, the Department of Molecular and Medical Pharmacology and the cancer center's Sarcoma Program, could lead to the development of new therapies that target the cell signaling pathway regulated by PTEN. A novel mouse model of neurofibromatosis type 1 (NF1) developed at UCLA first illustrated the importance of PTEN tumor suppressor in malignant transformation and this finding was validated in malignant peripheral nerve sheath tumors.

"The loss of expression of PTEN in the human sarcomas we studied mirrored the loss of PTEN in mice, and we anticipate being able to target this pathway abnormality for the development of new methods of diagnosis and treatment" said Dr. Fritz Eilber, director of the Sarcoma Program and an assistant professor of surgical oncology. "Within the sarcoma world, malignant peripheral nerve sheath tumors are one of the most lethal sub-types, so this is a significant finding and may lead to new and more effective treatments."

NF1 is one of the most common genetically inherited disorders, with an incidence of about 1 in every 2,500 births, said, Dr. Hong Wu, associate director of the molecular medicine institute, a Jonsson Cancer Center researcher and senior author of the study. "Patients with NF1 have an about 10 percent lifetime risk of developing this lethal sarcoma sub-type," Wu said.

The study also showed that Positron Emission Tomography (PET) scanning with the glucose analogue FDG - both in the mice and in humans - is a highly accurate way to distinguish between the benign tumors and the malignant ones, indicating that this non-invasive imaging technology is valuable in assessing therapeutic response to new treatments.

The mouse model was created by altering two cell signaling pathways that are commonly activated in peripheral and central nervous system cancers, the RAS/RAF/MAPK & PTEN/P13K/AKT pathways, known to regulate cell proliferation, survival and differentiation.

"When we began to generate mouse models to mimic different human cancers, we usually did gene-based analysis to see the relevance of a specific gene in the development of the cancer," Wu said. "But we realize that sometimes targeting the cell signaling pathways that organize and instruct cells to function, both for normal functions of our body and also in abnormal ways in disease, are more important and informative than the individual gene."

The mouse model developed benign neurofibromas, but then progressed to the deadly sub-type of sarcoma. The neurofibromas had half the normal levels of PTEN and the sarcomas had a complete loss of PTEN. Since PTEN is an important factor in suppressing cells from becoming malignant, this could provide an explanation for the sequence of the normal cells transforming into benign neurofibromas that could then transform into cancer.

Wondering if this was also the case in people, Dr. Wu collaborated with Eilber and pathologist Dr. Sarah Dry, director of the Institute of Molecular Medicine's Pathway Pathology Center, and a multidisciplinary team of physician-scientists to determine if people with this sarcoma sub-type also had little or no PTEN.

Currently, there are no effective treatments to prevent the benign NF1 tumors from transforming into cancer. The genetically engineered mouse model will be used to screen drugs that may be able to target the signaling pathway regulated by PTEN, to block signals that instruct the cells to change from a benign state to a malignant one, providing treatment options for patients with the deadly form of cancer.

"I think these findings will help us provide a better diagnosis that can determine if the neurofibroma is becoming a malignant tumor or not," Eilber said. "But more importantly, the loss of the PTEN and its associated signaling pathways gives us targets for therapy and it may lay the foundation for treatment in other sarcomas as well."

V6N6 ESUN Copyright © 2009 Liddy Shriver Sarcoma Initiative.