Gusscott Samuel, Tamiro Francesco, Giambra Vincenzo, Weng Andrew P
Terry Fox Laboratory, BC Cancer Agency, Vancouver, BC, V5Z 1L3, Canada.
Terry Fox Laboratory, BC Cancer Agency, Vancouver, BC, V5Z 1L3, Canada; Institute for Stem Cell Biology, Regenerative Medicine and Innovative Therapies (ISBReMIT), Fondazione IRCCS Casa Sollievo della Sofferenza, 71013, San Giovanni Rotondo, FG, Italy.
Adv Biol Regul. 2019 Dec;74:100652. doi: 10.1016/j.jbior.2019.100652. Epub 2019 Sep 15.
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive cancer, characterized by an uncontrolled expansion and accumulation of T-cell progenitors. During leukemic progression, immature T cells grow abnormally and occupy the bone marrow compartment, thereby interfering with the production of normal blood cells. Pediatric T-ALL is curable with intensive chemotherapy, but there are significant, long-term side effects and ~20% of patients suffer relapse for which there are limited treatment options. Adult T-ALL in contrast is largely incurable and refractory/relapsed disease is common despite multi-agent chemotherapy (5-year overall survival of ~40%), and thus new therapeutic targets are needed. We have reported previously on the role of insulin-like growth factor (IGF) signaling in T-ALL, and shown that it exerts potent phenotypes in both leukemia stem cell and bulk tumor cell populations. Modulators of IGF signaling may thus prove useful in improving outcomes in patients with T-ALL. In this review, we summarize the most recent findings relating to IGF signaling in T-ALL and outline therapeutic options using clinically relevant IGF signaling modulators.
T细胞急性淋巴细胞白血病（T-ALL）是一种侵袭性癌症，其特征是T细胞祖细胞不受控制地扩增和积累。在白血病进展过程中，未成熟T细胞异常生长并占据骨髓腔，从而干扰正常血细胞的生成。小儿T-ALL通过强化化疗可治愈，但存在显著的长期副作用，约20%的患者会复发，而针对复发的治疗选择有限。相比之下，成人T-ALL大多无法治愈，尽管采用多药化疗（5年总生存率约为40%），难治性/复发性疾病仍很常见，因此需要新的治疗靶点。我们之前报道了胰岛素样生长因子（IGF）信号在T-ALL中的作用，并表明它在白血病干细胞和大量肿瘤细胞群体中都发挥着强大的表型作用。因此，IGF信号调节剂可能被证明有助于改善T-ALL患者的预后。在这篇综述中，我们总结了与T-ALL中IGF信号相关的最新发现，并概述了使用临床相关IGF信号调节剂的治疗选择。
