Editorial: the long and winding road to better cancer cell-specific therapies.

In the last decade, our understanding of the molecular mechanisms underlying malignancies has greatly improved, not the least because of advances in molecular techniques. This has facilitated the development of multiple cancer cell–specific compounds such as tamoxifen and the aromatase inhibitors, and more recently, monoclonal antibodies and tyrosine kinase inhibitors (TKIs). These drugs, which inhibit the functional activity of “tumor-driving” factors, have resulted in superior outcomes for patients with common tumor types including breast and colorectal cancer. Soft tissue sarcomas (STSs) are a heterogeneous and rare group of tumors accounting for about 1% of all malignancies. Patients presenting with advanced disease have a poor prognosis, given a median overall survival time of approximately 1 year with the currently available treatment options. This stresses the need for more effective treatment. The group of STSs comprises 50 diverse histopathological tumor entities, which differ importantly between each other in terms of pathogenesis, clinical behavior, and sensitivity to systemic agents. Despite this heterogeneity, most STSs are treated in a similar way regardless of the exact histopathological subtype. In recent years, however, this approach has changed considerably because the insight has emerged that the different subtypes should be separately managed rather than similarly. That this is indeed the way to go has clearly been demonstrated by the successes obtained in gastrointestinal stromal tumors (GISTs), one of the STS subtypes. GISTs are driven by constitutive activation of c-Kit, a transmembrane receptor, the function of which can be blocked by the TKIs imatinib and sunitinib. These drugs have revolutionized the treatment outcome of advanced GIST patients, improving the 5-year overall survival rate from 20% to 50% [1, 2]. In this respect, it is certainly warranted to assess whether similar approaches that have proven to be so successful in GISTs apply to other STS entities as well. In the previous issue of The Oncologist, two papers addressed whether or not the epidermal growth factor receptor (EGFR), also known as the human epidermal growth factor receptor (HER)-1, is a valid drug target in synovial sarcoma, a disease accounting for 5%–8% of all adult STSs. The first paper was from Ray-Coquard et al. [3] on behalf of the Soft Tissue and Bone Sarcoma Group of the European Organization for Research and Treatment of Cancer. Because it was previously demonstrated that EGFR is overexpressed in a substantial number of synovial sarcomas [4, 5] and that the ligand of EGFR can induce proliferation in synovial sarcoma cell lines [6], the EGFR-targeting TKI gefitinib was screened for its antitumor activity in patients with synovial sarcomas. All patients included had EGFRexpressing synovial sarcoma and displayed progressive disease after standard chemotherapy. The primary endpoint of this study was the progression-free rate at 3 months. Currently, this is considered a more relevant endpoint [7] than response rates in phase II studies aiming to screen the antitumor activity of drugs such as gefitinib. It is increasingly being recognized that TKIs exert antitumor effects not only by inducing tumor shrinkage but also by stabilizing the size