In this issue of Blood, Mathewson et al characterized targeting a novel intracellular pathway with an agent known to induce potent antitumor effects but now also appears to potently suppress inflammatory responses by dendritic cells (DCs) and prevent graft-vs-host disease (GVHD). Identifying agents that can suppress GVHD yet not compromise graft-vs-tumor (GVT) effects remains a paramount goal in allogeneic hematopoietic stem cell transplantation (HSCT). So-called "small molecules" have started to dominate the clinical practice of cancer treatment with the promise of targeting the underlying molecular changes that are responsible for specific malignant phenotypes and avoiding the side effects of systemic chemotherapies. Increasing evidence has emerged to indicate that these drugs also can exert profound immunomodulatory effects on the immune system which makes them attractive in targeting GVHD.2 The study by Mathewson et al1 continues in that vein. MLN4924 was first described regarding its potent antitumor effects affecting a wide array of tumor types.
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