Predictive Biomarkers and Targeted Therapies in Sarcomas
Sarcomas are cancers arising from transformed cells of mesenchymal origin. According to the American Cancer Society 2018 statistics, about 13,040 new soft tissue sarcomas are expected to be diagnosed in the United States with 7370 cases in males and 5670 cases in females. About 5150 Americans (2770 males and 2380 females) are expected to die of soft tissue sarcomas. Sarcomas represent a genomically highly heterogenous group that in many cases share a similar clinical course. They are malignant tumors with locally aggressive growth, frequent local recurrences, or distant (mostly pulmonary) metastases. For localized disease, surgery represents the cornerstone of treatment with radiotherapy improving local control. Chemotherapy, which has been developed empirically, is greatly improving survival in bone sarcomas but is only moderately effective in some, by far not in all, soft tissue sarcoma subtypes. Targeting the underlying biology in sarcomas is beyond doubt the only measure to overcome the therapeutic standstill in the field. Predictive biomarker analyses are used to stratify patients and have come to play an enormous role in this area. This chapter will focus on predictive biomarkers in gastrointestinal stromal tumors and malignant soft tissue sarcomas. Basic principles of treatment modalities and diagnostic procedures will be covered.
KeywordsGastrointestinal stromal tumor GIST Soft tissue sarcoma Activating mutations Receptor tyrosine kinase Tyrosine kinase inhibitor Imatinib Resistance Gene fusion Sequencing
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