Checkpoint 1 Inhibition in AML
Cytarabine incorporation into DNA activates checkpoint kinase 1 (Chk1), induces S phase slowing, and leads to cytarabine resistance. The selective Chk1 inhibitor SCH 900776 overcomes CHK1 activation and enhances cytarabine cytotoxicity in acute leukemia cells in vitro. On this basis, Karp and colleagues conducted a phase I study of cytarabine and SCH 900776 in adults with resistant acute leukemias. The combination enhanced the DNA damaging effects of cytarabine in leukemic blasts and induced remissions in relapsed and refractory acute myeloid leukemias (AML). The data support a randomized phase II trial of cytarabine +/− SCH 900776 for adults with poor-risk AML.
AZD4547 Is Active in FGFR1-Amplified NSCLC PDTX Models
Deregulated FGFR expression plays an important role in driving many cancers. In this report, Zhang and colleagues identify FGFR1 gene amplification in a cohort of Chinese squamous cell carcinoma, in which effective treatment therapies are desperately needed. Utility for the novel and selective FGFR inhibitor, AZD4547, was shown through in vitro tumor cell proliferation studies, and importantly, translational significance was established by the observation of tumor stasis or regression effects in a panel of FGFR1-amplified squamous lung patient–derived tumor xenograft models, but not in nonamplified models. These data thus provide a strong rationale for the investigation of AZD4547 as a novel therapeutic option for NSCLC patients with tumors harboring FGFR1 amplification.
Sequential Use of 2 Oncolytic Viruses for Cancer Treatment
Oncolytic viruses have been developed as a new class of therapeutics for cancer. Although their clinical safety profiles are encouraging, the efficacy of oncolytic viruses as single-agent therapy has been limited. Tysome and colleagues developed a novel therapeutic regime using a sequential combination of oncolytic adenovirus and vaccinia virus. Not only does this regimen eradicate established tumors in immunocompetent animal models, but strikingly it also results in long-lasting tumor-specific immunity. These findings provide proof-of-concept support for the sequential use of oncolytic adenovirus and vaccinia virus as a powerful antitumor therapeutic modality that could be directly translated for use in cancer patients.
Reconstitution after Tandem Transplant
In this study, Grupp and colleagues show that autologous expanded T cells can provide productive host defense and can augment antibody responses to immunizations. This study improves our understanding of how patient-specific therapy could be offered to improve outcomes posttransplant in high-risk individuals.
- ©2012 American Association for Cancer Research.