See article by Khouri et al., p. 1011

Prevention or treatment of relapsed lymphoid malignancies after hematopoietic stem cell transplantation requires novel strategies. Khouri and colleagues show that the addition of lenalidomide to ipilimumab at 3 mg/kg for just two cycles can induce greater than expected and durable clinical responses. This impact also is suggested by the additive increased numbers of inducible costimulatory +CD4+ T cells by lenalidomide. The preliminary data indicate similar immune responses in the allogeneic and autologous transplant recipients. The treatment is safe, with no severe treatment-related toxicities, minimal immune-mediated toxicity and no graft-versus-host disease. Findings from this study support further investigation of this combination in this setting.

See article by Fang et al., p. 1048

Barrett's esophagus can be diagnosed and biopsied by esophagogastroduodenoscopy, but current screening and surveillance strategies are limited by the absence of specific imaging markers predictive of increased risk for esophageal adenocarcinomas (EAC). Fang and colleagues use a Barrett's esophagus mouse model and EAC patient data to demonstrate that the chemokine receptor 4 (CXCR4) is upregulated in the immune tumor microenvironment, thus presenting a highly attractive target for PET/CT imaging using CXCR4-targeted probes. These findings provide new insights into the kinetics and pathogenesis of EAC and introduce CXCR4-based imaging of the tumor microenvironment as a potential approach for diagnosis and surveillance of EAC.

See article by Hammerlindl et al., p. 1090

RAS-mutant cancer is difficult to treat with standard care. Nonsteroidal anti-inflammatory drugs like aspirin have been proposed to reduce cancer burden. Hammerlindl and colleagues describe combining aspirin with sorafenib, a multi-kinase inhibitor, in RAS-mutant melanoma and lung cancer. The combination induced activation of both AMPK and ERK pathways, leading to strongly enhanced tumor cytotoxicity at relatively low sorafenib doses. Combining aspirin and sorafenib is a viable treatment strategy in refractory and relapsed RAS-mutant cancer.

See article by Su et al., p. 1124

Effective therapies for glioblastoma, a cancer known to being highly resistant to chemotherapy, may have to target multiple tumor cell survival mechanisms. Su and colleagues investigated the mechanisms of action of TG02, a novel CDK9 inhibitor, as a single agent and in combination with temozolomide, utilizing in vitro and in vivo glioblastoma models. In addition to transcriptional suppression, TG02 also was found to induce mitochondrial dysfunction, glycolytic suppression, and, when combined with temozolomide, synergistically decreased energy production in glioblastoma. These results have led to an ongoing clinical trial investigating this promising therapeutic strategy in patients with recurrent glioblastomas (NCT02942264).