Preclinical experimental therapeutic approaches in soft tissue sarcoma

Soft tissue sarcomas are relatively rare tumors that are generally treated with a multimodality approach including surgery, chemotherapy, and radiatio n therapy. Despite this aggressive tri-modality therapy, greater than 50% o f soft tissue tumors will recur and result in diffuse metastatic spread of disease and ultimately death of the patient. It is this clinical scenario t hat drives the development of preclinical experimental studies designed to explore alternative treatments or enhance the effectiveness of existing the rapies. Rapid developments in the field of molecular biology have led to th e understanding of basic cellular processes governed by oncogenes and tumor suppressor genes. These: cellular genes are sometimes overexpressed, mutat ed or even deleted from tumor cells. Cytogenetic analysis has led to the di scovery of sarcoma fusion genes which encode for oncoproteins, peculiar to specific subtypes of soft tissue sarcomas. These fusion genes have proved t o be helpful in terms of diagnostic dilemmas and are now being used as targ ets in treatment strategies aimed at suppression of the cellular expression and action of these oncoproteins. Tumor suppressor genes such as p53 and t he retinoblastoma tumor suppressor play important roles in growth inhibitio n and cell cycle progression. These tumor suppressors are often mutated or deleted in soft tissue sarcomas. Using gene therapy stategies, p53 can be r eintroduced into:sarcoma cells and has been shown to result in a dramatic d ecrease in cell survival, It also appears that p53 may sensitize these tumo r cells to radiation and chemotherapy agents. Strategies which can drive tu mor cells into programmed cell death pathways are also showing promise as n ovel treatment approaches to soft tissue sarcomas. This review will highlig ht some, of the current research exploring novel treatment strategies aimed at molecular targets. Further development of these and other preclinical e xperimental programs are important in improving the outcome for patients wi th these rare soft tissue tumors. Semin Surg. Oncol. 17:78-82, 1999. (C) 19 99 Wiley-Liss, Inc.