Pediatric Adrenocortical Carcinoma Xenograft Model
Pinto et al. Page 1740
The rarity of pediatric adrenocortical carcinoma (ACC) presents significant challenges in developing more effective treatment options. Pinto and colleagues report the establishment of the first validated xenograft for studying childhood ACC. They tested a panel of common chemotherapeutic drugs in this experimental model and identified topotecan as a new cytostatic agent in the context of this tumor type. Notably, a child with ACC that had been refractory to standard therapy responded to topotecan as a single agent. These findings show promise that topotecan may be effective in treating ACC, warranting further clinical investigation.
Aurora Kinase A Inhibitor MLN8237 in Bladder Cancer
Zhou et al. Page 1717
The Aurora kinases are a family of serine/threonine kinases involved in the mitotic spindle checkpoint that have been found to be overexpressed in certain human cancers, including bladder cancer. In evaluating Aurora kinase A as a possible therapeutic target, Zhou and colleagues found that the Aurora kinase A inhibitor MLN8237 impairs cell viability and cell-cycle progression in human bladder cancer cells and exhibits antitumor activity in a mouse xenograft model of bladder cancer. This study identifies the Aurora kinases as potential drug targets in human bladder cancer.
JQ1 Represses Diverse Glioblastoma Tumors
Cheng et al. Page 1748
The genetic heterogeneity of glioblastoma represents a significant obstacle for developing effective targeted therapy. Cheng and colleagues show that pharmaceutical inhibition of proteins from the bromodomain and extraterminal domain (BET) family of epigenetic readers induces broad antineoplastic effects in glioblastoma tumors with different genetic backgrounds. They observed that these effects were mediated, at least in part, by widespread induction of CDKN1A and downregulation of BCL2L1. These results highlight the promise of emerging second-generation epigenetic drugs in complex solid tumors. Whether the BET bromodomain proteins represent an Achilles' heel for glioblastoma warrants further investigation.
Anti-CD19 Therapy in Childhood Leukemia Xenografts
Carol et al. Page 1795
CD19 is an almost universal surface marker of B-cell precursor acute lymphoblastic leukemia (ALL). The novel antibody–drug conjugate SAR3419, currently in clinical trials against adult CD19-positive malignancies, delivers the maytansinoid DM4 drug to its target population with high specificity. Carol and colleagues show the high efficacy of SAR3419 as a single agent against CD19-positive pediatric ALL xenograft models and report that the extent of response was correlated with the level of CD19 expression. In their study, when SAR3419 was administered as protracted therapy after remission induction with a regimen of established drugs, the combination prevented leukemia relapse into hematopoietic and lymphoid organs. These results provide the basis to combine SAR3419 with established drugs in high-risk ALL as a means to improve treatment outcomes.