Memorial Sloan Kettering Cancer Center, Lymphoma Service, New York, NY, USA.
Curr Hematol Malig Rep. 2019 Oct;14(5):405-413. doi: 10.1007/s11899-019-00540-w.
The outcome of patients with lymphoid malignancies has markedly improved in recent years which is likely due to a combination of advances in supportive care, and therapeutic options. In this article, we will provide an overview over the role PI3-kinase signalling, one of the most important dysregulated pathways in cancer, and its successful inhibition in lymphoma.
PI3-kinase inhibitors have shown remarkable activity in an increasing subset of patients with non-Hodgkin lymphomas. The first drug to be approved was idelalisib for patients with relapsed/refractory follicular lymphoma and CLL/SLL as monotherapy, or in combination with rituximab, respectively. After an initial setback related to increased toxicity including deaths observed in several upfront studies, there has been a resurgence in interest in this pathway following the promising efficacy of second-generation PI3K inhibitors including in patients with T cell lymphomas. PI3K inhibition continues to be an invaluable tool in the therapy of patients with lymphoid malignancies if managed cautiously. Preclinical models are helpful in predicting possible side effects and identifying new lymphoma subtypes that may be susceptible to this class of agents. The future will likely involve rationally designed combinatorial approaches to deepen the response rate and prevent the emergence of resistance.
近年来，淋巴恶性肿瘤患者的预后明显改善，这可能是由于支持治疗和治疗选择的进步。在本文中，我们将概述 PI3-激酶信号通路的作用，该通路是癌症中最重要的失调途径之一，及其在淋巴瘤中的成功抑制作用。
PI3-激酶抑制剂在越来越多的非霍奇金淋巴瘤患者亚群中显示出显著的活性。第一种获批的药物是idelalisib，可用于复发/难治性滤泡性淋巴瘤和 CLL/SLL 的单药治疗，或分别与利妥昔单抗联合治疗。在最初因包括几项前期研究中观察到的死亡在内的毒性增加而出现挫折后，第二代 PI3K 抑制剂（包括在 T 细胞淋巴瘤患者中）的疗效令人鼓舞，再次引起了人们对该途径的兴趣。如果谨慎管理，PI3 激酶抑制仍然是治疗淋巴恶性肿瘤患者的宝贵工具。临床前模型有助于预测可能的副作用，并确定可能对这类药物敏感的新的淋巴瘤亚型。未来可能涉及合理设计的组合方法，以加深反应率并防止耐药性的出现。
