New Therapeutic Targets in Alveolar Soft Part Sarcoma were revealed in a new study conducted by Dr. Ewa Sicinska from the Department of Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, and Dr. Matt Hemming from the Department of Medicine, Division of Hematology and Oncology, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA.

Using ASPS tumor samples and preclinical models, Drs. Sicinska and Hemming identified genes regulated by the ASPSCR1-TFE3 fusion protein, which drives ASPS cellular proliferation, angiogenesis, mitochondrial biogenesis, and suppression of differentiation.

Drs. Sicinska and Hemming found that ASPS relies on high expression of the Cyclin D1 protein, whose expression is controlled by ASPSCR1-TFE3. Additionally, they demonstrated in ASPS mouse models that ASPS is sensitive to CDK4/6 inhibition both in vitro and in vivo in a patient-derived xenograft (PDX) model. Moreover, treatment of ASPS xenografts with both CDK4/6 and VEGFR inhibitors had superior effects in restricting tumor growth compared to either therapy alone.

The importance of these findings is that they open new opportunities for potential clinical trials for ASPS patients, combining inhibitors of Cyclin D1/CDK4 signaling to achieve better therapeutic responses.

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Yosef Landesman, Ph.D.

President & Cancer Research Director

Cure Alveolar Soft Part Sarcoma International (iCureASPS)

e-mail: landesmany@yahoo.com