New Strategies in Sarcoma Therapy: Linking Biology and Novel Agents

Abstract

The ability to better interrogate the genetic state of a given cancer is giving rise to a new paradigm in cancer therapeutics in which the specific genetic alterations that give rise to the cancer inform the therapeutic decision-making for that specific patient. Sarcomas of soft tissue and bone represent model diseases that underscore this paradigm. However, many barriers prevent linkage of one of the 75 or more different types of sarcoma to novel therapeutic agents. In the present perspective, the authors outline key therapeutic opportunities and hurdles in clinical sarcoma research, focusing on specific examples of sarcomas that are on the verge of new breakthroughs, as well as those in which promise has not lived up to expectations. Focused clinical trial design, ideally with several biomarker or histology-specific arms, is one means to be simultaneously parsimonious and inclusive. Clin Cancer Res; 18(21); 5837-44. Ó2012 AACR.

Pediatric Malignant Bone Tumors: A Review and Update on Current Challenges, and Emerging Drug Targets

“…Its expression remains stable and is rarely lost under treatment pressure 48,55 and in some estimates is expressed in 95% of osteosarcomas. 56,57 Anti-GD2 monoclonal antibody therapy has significantly improved survival in neuroblastoma and based on this experience, this approach holds promise for the treatment of osteosarcoma.…”

The genomics of desmoplastic small round cell tumor reveals the deregulation of genes related to DNA damage response, epithelial–mesenchymal transition, and immune response

“…Desmoplastic small round cell tumor (DSRCT) is a very rare sarcoma arising from the abdominal/pelvic peritoneum that mainly occurs in young male adults and is included in simple sarcomas in the molecular sarcoma classification [ 1 ]. DSRCT is characterized by an ominous outcome as current aggressive polychemotherapies do not lead to a significant improvement in response and overall survival [ 2 ]; it is therefore included in the “most wanted” list of sarcomas requiring new agents [ 3 ].…”

HSP90 inhibition as a means of radiosensitizing resistant, aggressive soft tissue sarcomas

“…Soft tissue sarcomas include a broad range of rare tumors, which are usually attended by multidisciplinary treatment approaches [1]. For non-metastatic disease, surgery is a central cornerstone.…”