Despite complex genetics, aneuploid tumors like dedifferentiated liposarcoma have specific and reproducible chromosomal changes such as amplification of HDM2 and CDK4 that represent potential targets for systemic therapy. In addition, there are cancer cell survival pathways that may not be the target of chromosomal translocations or mutations that are still estimable targets for new systemic therapeutics, be it pathways involved in angiogenesis or apoptosis. In this review, we examine target selection for specific sarcoma subtypes, and demonstrate with a few examples new techniques being used to delineate novel therapeutic inroads for patients with sarcoma.
aSarcoma Program, Memorial Sloan-Kettering Cancer Center, New York, NY
bDepartment of Pathology, Stanford University Medical Center, Stanford, CA
cMolecular Pathology Program, Centro de Investigación del Cáncer–IBMCC, University of Salamanca–CSIC, Salamanca, Spain
dLaboratory of Experimental Molecular Pathology, Department of Pathology, Fondazione IRCCS, Istituto Nazionale Tumori, Milan, Italy
eSarcoma Oncology, Fox Chase Cancer Center, Philadelphia, PA
fLaboratoire de Génétique des Tumeurs Solides, Faculté de Médecine, Centre Hospitalier Universitaire de Nice et CNRS UMRS 6543, Nice, France
gMaria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Department of Soft Tissue/Bone Sarcoma and Melanoma, Warsaw, Poland
hResearch Division, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia
Address correspondence to David M. Thomas, FRACP, PhD, Research Division, Peter MacCallum Cancer Centre, St Andrew's Place, East Melbourne, Victoria 3002, Australia
Enrique de Alava is supported by the European Commission (NoE EuroBoNet), Ministry of Science and Innovation of Spain-FEDER (PI052524, RD06/0020/0059). Silvana Pilotti is supported by Associazione Italiana per la Ricerca sul Cancro (AIRC). Robert G. Maki is supported by Program Project Grant No. P01-CA47179; Cycle for Survival. David M. Thomas is supported by the Victorian Cancer Agency Clinician Researcher fellowship, and Cancer Australia.
DisclosuresRobert G. Maki: Research support (Pfizer); honoraria (Ziopharm); testimony (Roche)
Margaret von Mehren: Research support (Novartis, Pfizer, Johnson & Johnson); consultation fees (Novartis, Pfizer, Medimmune)
David Thomas: Research support (Novartis, Amgen, Pfizer)
1,2 These authors contributed equally to this work.
ABSTRACT