Cure Alveolar Soft Part Sarcoma International (iCureASPS)

The third annual Knockin’ Down ASPS Event in the memory of Anthony Salisbury (AJ) took place in May. This year, over $12,000 was raised and donated directly to the laboratory of Dr. Glenn Dranoff at the Dana Farber Cancer Institute in Boston to support his efforts in finding a cure for Alveolar Soft Part Sarcoma.

Cure Alveolar Soft Part Sarcoma International, and the Alveolar Soft Part Sarcoma community extend our thanks to the Knockin’ Down ASPS committee, participants, and donors. Special thanks and wishes to Kim. Your support enables progress towards the so much needed ASPS cure!

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Yosef Landesman, Ph.D.
President & Cancer Research Director
Cure Alveolar Soft Part Sarcoma International (iCureASPS)
e-mail: landesmany@yahoo.com

An experimental drug, cediranib, may benefit alveolar soft part sarcoma (ASPS) patients, according a recent clinical trial. The trial, carried out by scientists at the National Cancer Institute (NCI), part of the National Institutes of Health, showed that tumors shrank in more than 50 percent of ASPS patients who were treated with cediranib. These findings were presented at the American Society of Clinical Oncology’s annual meeting in Chicago on June 6, 2011.

ASPS accounts for less than one percent of soft tissue sarcomas, and forms in tissues that connect, support, or surround the organs of the body. It is usually diagnosed in children and young adults, developing as a painless mass in the leg or buttock.

ASPS arises due to the breaking and joining of two chromosomes in tumor cells. An X chromosome, one of two sex chromosomes in humans, and one copy of chromosome 17, each lose a small piece, and the X chromosome piece becomes joined to the rest of chromosome 17. This process, called a chromosomal translocation, creates a fusion between two genes, ASPL (on chromosome 17) and TFE3 (on the X chromosome).When this fusion gene is expressed, the result is the formation of an aberrant fusion protein, ASPL-TFE3, not found in normal cells. The detection of this protein is used to confirm a diagnosis of ASPS, which is crucial in distinguishing it from other soft tissue sarcomas, but the protein’s exact role in disease progression is still unknown.

Even though researchers do not know the exact function of the fusion protein in this disease and therefore cannot target it directly, they do know that the cancer relies on the formation of new blood vessels to allow it to grow and spread throughout the body, especially the lungs, where multiple small nodules form. Because of this reliance on the vasculature (arrangement of blood vessels in the body), scientists decided to test cediranib in ASPS, since it’s a drug that blocks the formation of new blood vessels.

AstraZeneca, the drug’s manufacturer, has tested the effect of cediranib in treating a variety of tumors, including lung and colorectal cancers. ASPS is the first solid tumor that has demonstrated substantial tumor shrinkage. NCI’s Division of Cancer Treatment and Diagnosis (DCTD) supported the initial development of this drug using a cooperative research and development agreement, which is a contract between NCI and industry to further develop a technology for commercialization.

“It is unusual to see such high levels of tumor shrinkage in a cancer that traditionally has not responded to standard chemotherapy used for the treatment of sarcomas,” said Shivaani Kummar, M.D., head of early clinical trials development in DCTD. Standard chemotherapy for ASPS has shown no benefit or response.

In this trial, 33 patients ranging in age from 19 to 59 received cediranib. Of these, more than 50 percent had tumor shrinkage, and some continued to receive the treatment more than a year later.

Importantly, the reported side effects of cediranib, that include hypertension and diarrhea, were manageable.

The collaborative abilities of two of NCI’s divisions, DCTD and NCI’s Center for Cancer Research (CCR), played an important role in evaluating this new agent’s potential for the treatment of this rare tumor. The ability to bring ASPS patients from across the country to CCR’s clinical facility on the NIH campus for treatment made patient accrual for a trial in this rare tumor possible, according to Kummar.

A follow up study, coordinated by NCI and conducted at the NIH Clinical Center and at several other research facilities, including two NCI-designated Cancer Centers — Dana-Farber Comprehensive Cancer Center in Boston, and M.D. Anderson Comprehensive Cancer Center in Houston — is planned to confirm these promising results. The trial will compare cediranib with sunitinib, another blood vessel growth inhibitor, in patients with ASPS.

NCI leads the National Cancer Program and the NIH effort to dramatically reduce the burden of cancer, and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI Web site or call NCI’s Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

Reference: Phase II study of cediranib (AZD2171) in patients with alveolar soft part sarcoma. To learn more visit: http://1.usa.gov/la6iqN.

Dr. Shamini Selvarajah presented a summary of her studies on Alveolar Soft Part Sarcoma at the 2011 ACMG Annual Clinical Genetics Meeting that took place at the Vancouver Convention Center, Vancouver, BC, Canada. Dr. Selvarajah is one of the dedicated scientists from the Dana Farber Cancer Institute in Boston. They study ASPS relentlessly, aiming to understand the biology of this tumor and develop novel therapies which are in such a need for ASPS patients.

The work presented at the ACMG meeting included the identification of 323 genes which are specifically expressed in Alveolar Soft Part Sarcoma tumors. 207 of these genes are mostly abundant in the primary, and 116 of them are mostly abundant in ASPS metastases of 12 patients whose tumors were analyzed in this study. The 323 genes represent 16 key biological processes, gene signatures, and pathways that can be targeted in future studies.

iCureASPS will continue to support this research at the Dana Farber Cancer Institute through efforts of our Team ASPS participating in the PMC bike ride, and through generous donations from friends and family members of the large ASPS community.

To see the presentation of this study, follow the link - Identification of neural stem cell gene expression signatures associated with disease progression in alveolar soft part sarcoma by integrated molecular profiling

Shamini Selvarajah^1,2, Pyne Saumyadipta², Eleanor Chen¹, G. Petur Nielsen³, Glenn Dranoff², Edward Stack², Massimo Loda^1,2 and Richard Flavin^1,2

^[1]Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115;
^[2]Center for Molecular Oncologic Pathology, Dana–Farber Cancer Institute, Boston, MA 02115;
^[3]Massachusetts General Hospital, Boston, MA 02114

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Yosef Landesman, Ph.D.
President & Cancer Research Director
Cure Alveolar Soft Part Sarcoma International (iCureASPS)
e-mail: landesmany@yahoo.com

Since its inception, the iCureASPS organization has transferred more than a quarter million dollars to keep up research, and clinical trials that aim to find a cure for ASPS. I would like to thank the ASPS community, friends, and family who are supporting us in our goal of finding a cure for ASPS.

Please make a new year resolution now to continue helping us to reach our goal of eradicating ASPS. Help us locate research centers which would join our quest for a cure, and then organize a fund raiser where the donations will be sent directly to the research institution of your choice. Alternatively, join the Team ASPS fund raiser, and our PMC bike ride in Massachusetts this summer!

The registration for the 2011 PMC bike ride is now open. The ride will take place on August 6 and 7. This year marks the 8th time Team ASPS will participate in the ride. We are looking for more riders to join our team. The PMC is a bike-a-thon that crosses Massachusetts to raise money for cancer research and clinical trials at the Dana-Farber Cancer Institute in Boston. Donations, raised by Team ASPS, are restricted for research and clinical trials that aim to find a cure for Alveolar Soft Part Sarcoma.

You can join us as a rider, or as a virtual rider. If you cannot join, us please consider sponsoring our team. The PMC has a nonprofit organization status and donors will receive PMC receipts.

Please do not hesitate to contact me with question and ideas.

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Yosef Landesman, Ph.D.
President & Cancer Research Director
Cure Alveolar Soft Part Sarcoma International (iCureASPS)
e-mail: landesmany@yahoo.com

Scientists from the group of Dr. Massimo Loda reported the results of an extensive study that aims to identify potential therapeutic targets for ASPS last Friday.

The research team, comprised of Shamini Selvarajah (PhD), Eleanor Chen (MD, PhD), and Saumyadipta Pyne (PhD), used cDNA microarray technology (gene expression array) to examine the expression of 18,401 genes in primary, and metastatic ASPS tumors from 14 ASPS patients. The work was done in collaboration with Brigham and Women’s Hospital, and the Broad Institute, affiliated with the Massachusetts Institute of Technology, and Harvard University.

Significant gene expression changes were discovered in 1,063 genes. The team elected to focus on 323 of them, which were singled out for their dramatically increased (or decreased) expression from the time the ASPS tumor was a primary (original tumor) to the time it turned into a metastasis. In other words, this work identified genes (those genes turn into proteins in the tumor) that changed their expression, as the tumor increased in aggressiveness. Such genes are well suited to be targeted as a therapeutic modality. Initial analysis of those genes points to several known molecular pathways that contribute to tumor growth and angiogenesis (formation of new blood vessels) in other types of cancers. The next challenge will be to identify the most promising target genes, for which approved drugs already exist. As an initial next step, these drugs could then be tested in animal tumor models of ASPS, and in ASPS cell lines.

Dr. Glenn Dranoff is an active participant, and collaborator in this project. Dr. Dranoff developed the GVAX vaccine, and ran the first GVAX clinical trial for ASPS patients. He will continue to be involved in the efforts to find a cure for ASPS.

Dear ASPS patients, friends and family members! We need your help to continue supporting the science behind results like this one. Through cutting edge research, more groundbreaking findings will be made that will bring a cure for ASPS. You can help, and be part of these great efforts.

Please:

1.   Consider fund-raising and donations to support the efforts to find a cure for ASPS at the Dana-Farber Cancer Institute.

2.   Encourage patients who are planning surgeries to donate their tumors to the Dana Farber.

3.   Communicate with me in regards to both of the above to ensure that funds and tumor donations reach their destination.

We are thankful to Dr. Massimo Loda and the scientists who did this important work, Dr. Glenn Dranoff, Dr. Ewa Sicinska, and the administrative staff Marcia Izzi and Laurie Peterson.

iCureASPS will continue to support these studies through direct funding, and through Team ASPS with the Pan Mass Challenge, as we believe that this is the way to discover the much needed cure!

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Yosef Landesman, Ph.D.
President & Cancer Research Director
Cure Alveolar Soft Part Sarcoma International (iCureASPS)
e-mail: landesmany@yahoo.com