There has been noteworthy progress in molecular characterisation and therapeutics in soft tissue sarcomas. Novel agents have gained regulatory approval by the FDA. Examples are the tyrosine kinase inhibitors avapritinib and ripretinib in gastrointestinal stromal tumours (GIST), the immune check point inhibitor atezolizumab in alveolar soft part tissue sarcoma, the γ-secretase inhibitor nirogacestat in desmoid tumours, the NTRK inhibitors larotrectinib and entrectinib in tumours withNTRKfusions, the mTOR inhibitor nab-sirolimus in PEComa, and the EZH-2 inhibitor tazemetostat in epithelioid sarcoma. The FDA has also recently granted accelerated approval for autologous T-cell therapy with afami-cel in patients with HLA-A*02 and MAGE-A4-expressing synovial sarcoma. There are other promising treatments that are still investigational, such as MDM2 and CDK4/6 inhibitors in well-/dedifferentiated liposarcoma, immune checkpoint inhibitors in the head and neck angiosarcoma and a subset of patients with undifferentiated pleomorphic sarcoma, and PARP inhibitors in leiomyosarcoma. The challenges in drug development in soft tissue sarcoma are due to the rarity and the molecular heterogeneity of the disease and the fact that many subtypes are associated with complex karyotypes or non-targetable molecular alterations. We believe that progress maybe possible with a better understanding of the complex biology, the development of novel compounds for difficult targets such as proteolysis targeting chimeras (Protacs), the utilisation of modern clinical trial designs, and enhanced collaboration of academia with industry to develop treatments with a strong biologic rationale.
软组织肉瘤的分子特征研究和治疗领域已取得显著进展。多种新型药物已获得美国食品药品监督管理局（FDA）的监管批准。例如：酪氨酸激酶抑制剂阿伐普利尼和瑞普替尼用于胃肠道间质瘤（GIST），免疫检查点抑制剂阿特珠单抗用于腺泡状软组织肉瘤，γ-分泌酶抑制剂尼洛加司他用于硬纤维瘤，NTRK抑制剂拉罗替尼和恩曲替尼用于NTRK融合肿瘤，mTOR抑制剂纳米西罗莫司用于血管周上皮样细胞肿瘤（PEComa），以及EZH-2抑制剂他泽司他用于上皮样肉瘤。FDA近期还加速批准了针对HLA-A*02和MAGE-A4表达滑膜肉瘤患者的自体T细胞疗法阿法米-Cel。其他具有前景的治疗方案仍处于研究阶段，例如MDM2和CDK4/6抑制剂用于高分化/去分化脂肪肉瘤，免疫检查点抑制剂用于头颈部血管肉瘤及部分未分化多形性肉瘤患者，以及PARP抑制剂用于平滑肌肉瘤。软组织肉瘤药物开发面临的挑战源于该疾病的罕见性、分子异质性，以及许多亚型伴随复杂核型或不可靶向的分子改变。我们相信，通过深入理解复杂生物学机制、开发针对难治靶点（如蛋白水解靶向嵌合体）的新型化合物、采用现代化临床试验设计，并加强学术界与产业界的合作以开发具有坚实生物学依据的治疗方案，该领域有望取得进一步突破。
肿瘤(癌症)患者之家