Progress Report 2010

Alan Rosenthal Research Fund | Memorial Sloan-Kettering Cancer Center
Principal Investigators: Mary Louise Keohan, M.D. & Cristina Antonescu, M.D.

Hemangiopericytoma is a type of solitary fibrous tumor (SFT). SFT's can develop anywhere in the body, and generally follow a benign clinical course. However, in fifteen to twenty percent of cases, patients either progress with local malignant recurrence or distant metastasis. Current clinical treatment of primary tumors is surgery alone--and no effective therapies exist for metastatic or advanced disease.

The biological drivers of SFT growth remain unclear, primarily because the disease lacks recurrent genetic abnormalities. Several studies have failed to identify a consistent pattern of anomalies - they revealed gains or losses in chromosomes, as well as structural rearrangements, but nothing dramatic or constant.

The main objective of our investigation is to identify targets for cancer therapy development. By isolating the specific events, genetic variances, hormone over- and under-activity, etc., that drive SFT's, we can identify vulnerability in the tumor that can be exploited therapeutically - halting or slowing its growth.

Toward this end, we profiled the gene expression of 23 SFT's, and compared their genetic signature to 34 soft tissue sarcomas spanning seven subtypes. The SFT's did have a distinct genetic expression signature - with over-expression of cell surface receptors DDR1, ERBB2, and FGFR1 - gathered in a tight genomic cluster, separate from all other sarcoma subtypes. However, as in all previous studies, no activating mutations were identified by DNA sequencing.

Fortunately, a number of over-expressed hormones were pinpointed-including IGF2, an insulin-like growth hormone uniformly detected regardless of the tumor's location. Several studies point to the excessive release of IGF2 as playing a pivotal role in the most aggressive SFT's. For example, a small subset of SFT patients present with IGF2-related hypoglycemia, known as Doege-Potter syndrome, which is also associated with large tumor size or metastatic clinical behavior.

Looking ahead, our ultimate goal is to bring new treatments and renewed optimism to hemangiopericytoma patients and their families. Now that we have identified potential therapeutic targets, we seek to test existing drugs that may work against them - or develop new pharmaceutical approaches that manipulate tumor drivers.

On behalf of Memorial Sloan-Kettering Cancer Center--and our entire research team--please accept our sincere gratitude for your support of the Alan Rosenthal Research Fund in Hemangiopericytoma. We hope our progress report demonstrates the tangible advances made possible because of your generosity -thank you for nurturing our most promising investigations.