Patel Shreyaskumar R
From the Sarcoma Center, The University of Texas MD Anderson Cancer Center, Houston, TX.
Am Soc Clin Oncol Educ Book. 2014:259-62. doi: 10.14694/EdBook_AM.2014.34.259.
Much of the progress in systemic therapy for sarcomas was accomplished in the first half of the last 5 decades. Various chemotherapeutic agents were tested in the 70s through the 80s and became part of the standard of care for this patient population. During the decade of the 90s, dose intensification became feasible as a result of improved supportive care and the availability of growth factors, thus maximizing the therapeutic potential of this class of agents. However, response rates and survival plateaued and it became obvious that newer and mechanistically different agents were needed to improve the therapeutic index and gain further enhancement of outcomes. Since early 2000, primarily inspired by the experience with imatinib in gastrointestinal stromal tumors (GISTs), several targeted therapies have been tested in sarcomas with modest success. The major limitations encountered include the lack of drivers and actionable targets for bone and soft tissue sarcomas with complex genomic profiles. Continued investigations and sequencing of larger numbers of these rare and heterogeneous malignancies could shed some light on a path toward improved outcomes.
肉瘤全身治疗的大部分进展是在过去50年的前半期取得的。20世纪70年代到80年代期间，人们对各种化疗药物进行了测试，这些药物成为了该患者群体标准治疗的一部分。在20世纪90年代，由于支持治疗的改善和生长因子的可得性，剂量强化变得可行，从而使这类药物的治疗潜力最大化。然而，缓解率和生存率趋于平稳，显然需要更新的、机制不同的药物来提高治疗指数并进一步改善疗效。自2000年初以来，主要受伊马替尼治疗胃肠道间质瘤（GIST）经验的启发，几种靶向治疗方法在肉瘤中进行了测试，取得了一定的成功。遇到的主要限制包括缺乏驱动因素以及针对具有复杂基因组特征的骨肉瘤和软组织肉瘤的可操作靶点。对大量此类罕见且异质性恶性肿瘤的持续研究和测序可能会为改善治疗结果的途径提供一些线索。
