SUMMARY: Researchers at UCLA’s David Geffen School of Medicine and the UCLA Sarcoma Program have identified a treatment combination which utilizes Mocetinostat in conjunction with chemotherapy for the selective treatment of rhabdomyosarcoma. BACKGROUND: Sarcomas are a heterogeneous group of tumors arising throughout the body’s connective tissues such as bone, muscle, joints, and fat tissue. There are over 50+ subtypes of sarcoma, each with distinct histological and molecular features. Among these, rhabdomyosarcoma, one of the most prominent subtypes, can affect both children and adults. Rhabdomyosarcoma can be further divided into alveolar, embryonal, spindle cell/sclerosing, pleomorphic depending on origin such as head and neck, urinary organs, legs and arms, and paratesticular area. For rhabdomyosarcomas that cannot be removed surgically, chemotherapeutics are the current standard of care; however, for patients with recurrent rhabdomyosarcomas or those with limited sensitivity to classical chemotherapeutic treatment, limited alternatives are available. Because of the limited other therapeutic options available for treatment of rhabdomyosarcomas, it is considered an area of unmet need. To address this need, researchers at UCLA created a panel of various sarcoma cell-lines with which was used to screen and pilot novel compounds and combinations to identify new therapeutic approaches. INNOVATION: Using their novel screening methodology, UCLA researchers from the David Geffen School of Medicine and the UCLA Sarcoma Program have discovered a combination therapy approach for selectively treating rhabdomyosarcoma. This treatment employs Mocetinostat, a benzamide histone deacetylase inhibitor, in combination with additional systemic agents and/or clinically established therapeutics. This approach was shown to inhibit growth of various sarcoma cell-lines and selectively kill rhabdomyosarcoma lines when compared to controls or single-agents. Further validation performed in-vivo with immunocompromised mice and patient derived cell-lines recapitulated these findings. Together this Mocetinostat and chemotherapeutic combination has greater efficacy for treatment of rhabdomyosarcoma than current methods and shows promise for treatments in other sarcoma subtypes. POTENTIAL APPLICATIONS: • Treatment of rhabdomyosarcoma • Treatment of other sarcomas • Combination with chemotherapy ADVANTAGES: • Selective growth inhibition of rhabdomyosarcoma • More effective than standard chemotherapeutic treatment alone • Mocetinostat already has extensive therapeutic validation • Combination approach uses already established chemotherapy drugs DEVELOPMENT-TO-DATE: Mocetinostat and its effectiveness as a treatment for rhabdomyosarcoma has been evaluated through cell line screen and in-vivo mouse experiments. Subsequent experiments have also resulted in additional guidelines for combination with approved chemotherapeutic drugs.