Alveolar Soft Part Sarcoma Tumor Metabolizes Lactate by Goodwin and Jin et al in “Cancer Cell” Journal

Cancer Cell 26, 851-862, December 8,2014

The research from the group of Dr. Kevin Jones from the university of Utah was published in December 2014. It gives very important information on the metabolism of ASPS. It demonstrates that lactate drives proliferation of ASPS.

The full paper is available here.

The researchers initiated the study by creating transgenic mice carrying the ASPS gene in all of their cells. In patients this gene (ASPSCR1-TFE3) is found only in tumor cells. As expected this gene induced the formation of rapidly growing tumors. Unexpectedly, the ASPS tumors formed only in the heads of these mice. Every transgenic mouse developed a tumor within the skull, but never in the extremities (legs or hands) where usually patient ASPS tumors form. Close analysis of the tumors showed that these tumors had the same histopathology of human ASPS.

Next, the researchers identified the 500 most abundant genes expressed in the mice tumors and found them to be similar to those that were reported in human ASPS. As expected some of the genes are in pathways as “cell division” and “cell cycle”. However some of these genes belong to the “carbohydrate metabolism” pathway. This was another unexpected finding.

The surprise did not ended here: In addition to the fact that the ASPS in mice developed only in their heads, the researches found these tumors within skeletal muscles, although it was clear that the tumor origin did nor arise from muscle.

Then the researchers made few important findings explaining the above-unexpected observations. They found that the normal cells in the microenvironment of the tumors drove the formation of the tumors in the mice heads. The researchers discovered that ASPS tumors need the metabolite lactate for growth. Both brain and muscle are producing lactate flux. ASPS tumor cells then absorb this lactate and use this metabolic substrate as their energy source. Helping the ASPS tumors to uptake lactate are the MCT1 transporters and their binding partner CD147 protein. Those transporters are highly expressed by ASPS cells.

Finally, the researchers found that when they inhibited the lactate transporters MCT1 with a specific drug inhibitor namely CHC they could inhibit lactate signaling effects.

The researchers concluded that their research opened the door for exploring possible metabolic treatments for ASPS patients that could reduce the ability of ASPS to benefit from lactate which is available in their microenvironment.

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

Research on ASPS presented at the conference of the “American College of Medical Genetics”

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.photo.jpg

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

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Shamini Selvarajah1,2, Pyne Saumyadipta2, Eleanor Chen1, G. Petur Nielsen3, Glenn Dranoff2, Edward Stack2, Massimo Loda1,2 and Richard Flavin1,2

[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

______________________________________________________

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

Tumor Expression Profile of Alveolar Soft Part Sarcoma May Pave the Way for New Treatments at The Dana Farber Cancer Institute

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

Second Fundraiser in the Memory of Anthony Salisbury (AJ)

On January 26 2009, we lost Anthony Salisbury (AJ) to ASPS. AJ’s fiancée, family and friends remain committed to finding a cure for ASPS. In February 2009, they organized “Knockin’ Down ASPS”, the first fundraiser in AJ’s memory. This year, on Saturday, April 10, the second AJ memorial fundraiser, “Knockin’ Down ASPS” will take place. Donations will support the ongoing research studies of Dr. Glenn Dranoff at the Dana Farber Cancer Institute in Boston. Dr. Dranoff developed the first cancer vaccine (GVAX) clinical trial for ASPS patients. The results of this ongoing research will hopefully lead to the opening of another clinical trial. Please click the thumbnail below to read the full details. We thank the organizers of the fundraiser, and all of you who will participate and donate in favor of our efforts to find cure for ASPS.

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______________________________________________________

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

Team ASPS Races in PMC 2009 to Raise Funds for a Cure

During the first weekend of August, Team ASPS participated in their sixth Pan-Massachusetts Challenge (PMC) bike ride. This bike-a-thon 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.

I am very pleased to announce that this year Cure Alveolar Soft Part Sarcoma International and Team ASPS raised a total of $42,160. All donations are transferred to support ASPS research in the laboratories of Dr. Glenn Dranoff and Dr. Massimo Loda at the Dana Farber Cancer Institute. Dr. Glenn Dranoff, who developed the GVAX clinical trial for ASPS patients, continues his studies to develop better cancer vaccine approaches. Dr. Massimo Loda does research that aims to identify new targets for therapy through the analysis of ASPS tissue samples.

I would like to extend my thanks to Team ASPS 2009, our donors, friends, family members, and to the ASPS community, for helping us in our fight to find a cure! Photos from the Team ASPS PMC 2009 bike ride below are courtesy of David Eisenberg. See more in the Facebook group dedicated to Team ASPS.

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______________________________________________________

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

Team ASPS dedicated a 50-mile bike ride to the Team Sarcoma Initiative

Team iCureASPS dedicated a 50 mile bike ride to the 2008 Team Sarcoma Initiative. The ride was on the route between Wellesley and Wrentham, MA. It was the last training session for our riders who are preparing for the PMC bike ride that will take place during this coming weekend. The international sarcoma awareness week (July 12-20) is a project of the “Liddy Shriver Sarcoma Initiative” which was founded by Bruce Shriver. During that week, over 6,000 people participated in over 70 sports events in 14 countries! The goal of the project is to increase awareness and collect the very needed funds for research and clinical trials for sarcoma. To read more about the Team sarcoma Initiative please click this link.

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Matthew Scott Pinson – first Memorial Event – January 2007

Sunday, January 14th was the coldest day in the metropolitan Phoenix area if the past 17 years. It did not dampen the spirit of the runners assembled for the PF Chang’s Rock N Roll marathon. Temperatures at the start were approximately 27 degrees.

Two runners participated in the half marathon in support of Team ASPS and in loving memory of Matthew Scott Pinson. Danna Quinn, Matt’s mom, and Andreia Griego, a coworker and supporter, each completed the race. Andreia managed to finish in less than 2 hours, an excellent accomplishment. The race was an inspiration for not only the runners, running for many different causes and charities, but for the spectators as well, braving the cold to cheer on their family and friends.


It is a testament to Matt’s life that so many felt moved to contribute. I want to send my thanks to everyone. I am most appreciative of everyone’s support. Your generous donations helped to raise over $5,400. Thanks to those that supported Andreia and myself, to those that raised money in their own work places, from business partners, even at the race track. It is truly amazing what we can accomplish together.

Watch for details for next year’s event. Get out those running shoes and start training!

With hope that we find a cure,
Danna Quinn, mother of Matt

Dear Alveolar Soft Part Sarcoma Patients, Family, and Friends, Welcome to your New Home in Cure Alveolar Soft Part Sarcoma International

Our new organization aims to bring together ASPS patients, their families and friends who have a shared interest to find a cure for Alveolar Soft Part Sarcoma (ASPS). On this website you will find updated information about research and therapies for ASPS. You will get a chance to share your experience and information about your disease and your treatments with the ASPS community all over the world. Using the Forum on this website you will get the option to ask questions that will help you to make decisions regarding treatments of your ASPS. We are here to support you, your family, and friends. The network generated by communicating with patients and families all over the world helps us unite and learn more about this very rare disease and is key to the success of finding a cure.

The active Board members of Cure Alveolar Soft Part Sarcoma International are four members each with loved ones struggling with this disease.

Let me please introduce our board members:

Patient and Family Worldwide Support and Outreach Director – Ms. Bonni Hess (WA, USA)

Bonni is very well rooted inside the ASPS community. While serving on the Board of TAAASPS she devoted her time, energy, and passion to provide information, help, support and encouragement to ASPS patients, family members, and their caring friends. Bonni also worked closely with her husband Jim, and several family members, to proudly raise large sums towards the opening of the future Cancer Vaccine Trial at the Memorial Sloan Kettering Cancer Center in NY. Bonni continually encouraged everyone in the ASPS Community to more actively participate in the TAAASPS organization, the Web site, and vitally important fundraising endeavors.

Treasurer and Legal Affairs Director – Ms. Eva Mitchell (WA, USA)

Eva and her family are very involved members in the ASPS community. Eva also worked closely with her sister Carla Stratford, while she was on the Board of TAAASPS and together they also collected funds dedicated to the opening in the future of a Cancer Vaccine Trial at the Memorial Sloan Kettering Cancer Center in NY.

Clinical Therapy and Information Resource Director – Ms. Olga Tkatcheva, BSc (BC, Canada)

Olga is well-known in the ASPS community. Her very bright comments regarding current treatments for ASPS were very helpful to many of us during our struggle with ASPS. In addition, her relentless searches in the scientific literature have improved the knowledge of ASPS treatment options and added many original ideas that have become a strong tool in our fight for a cure.

President and Cancer Research Director – Yosef Landesman, PhD (MA, USA)

While serving as the Cancer Research Director on the Board of TAAASPS, I made the contact with two world-class laboratories at the Dana Farber Cancer Institute who started research programs on Alveolar Soft Part Sarcoma. Those successful ongoing studies led to the current first ever ASPS-specific Cancer Vaccine Clinical Trial. Additional clinical trials for our community may be offered at the Dana-Farber in the future. As a member in TAAASPS, I was part of the ongoing scientific interactions with the team at the Memorial Sloan Kettering in New York towards the preparation of the ASPS Peptide Cancer Vaccine. I personally mediated the shipment of fresh and preserved ASPS tumors from patients for preclinical studies and research at the Dana-Farber Cancer Institute, and in the laboratory of Dr. David Vistica in the National Cancer Institute. In addition, I managed the TAAASPS website and made sure that this site contains updated scientific information regarding ASPS research and treatment options. And last, but not least, during the last three years, our PMC bike ride team of the Boston area has been raising funds to sponsor the Dana-Farber Cancer Institute efforts towards the above-mentioned ongoing Clinical Trial and Research Activities.

Please surf our website and send us your comments. Use this website and learn about your disease. ASPS is a very rare disease and very limited funds are currently dedicated to find a cure for it. However, if we share our resources and work together, we will reach our goal: Cure ASPS!

__________________________

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