The Long and Winding Road to Better Cancer Cell-Specific Therapies

摘要

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 histopathologicaltumor 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 histopathologicalsubtype. 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 ofwhich 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.