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View the Table of Contents for the December 15 issue of Clinical Cancer Research.
Rosell et al. Page 7222 Riely et al. Page 7232 Ono et al. Page 7242 Brandt et al. Page 7252 Nicholas et al. Page 7261
Epidermal growth factor receptor (EGRF) mutations are the paramount discovery in the field of lung cancer, opening the gates to curability and new avenues of research in a small subgroup of nonsmokers with non-squamous cell carcinoma. In this CCR Focus, Guest Editor Rafael Rosell has invited several experts to compile and interpret the growing body of accumulated data on this topic that quite often generates confusion among physicians. The paradigm that EGFR inhibition is successful only in cancers in which an activating mutation is observed is examined as a starting point, before exploring EGFR as a target in cancers in which ATP-binding domain mutations have not been found. It is hoped that this CCR Focus topic will encourage a greater understanding of the alternative mechanisms needed to develop effective therapies.
Kitano et al. Page 7397
CHP-HER2 complex vaccine, a truncated 1-146 HER2 protein vaccine using a novel antigen-delivery system, nanogels of cholesteryl pullulan, was given to HER2-expressing cancer patients. HER2-coding mRNA-transduced CD4+ T cells were used as antigen-presenting cells in ELISPOT assay, allowing the detection of overall T-cell responses to both defined and unidentified T-cell epitopes derived from a target antigen molecule. The vaccine was safe and induced HER2-specific immune responses, including CD8+ and CD4+ T-cell responses. This system could be applied to the development of a protein cancer vaccine targeting various categories of tumor antigens.
Feltquate et al. Page 7414
The bulk of the apoptotic events following androgen depletion therapy (ADT) for prostate cancer occur soon after the initiation of treatment. This suggests that multiple rapid cycles of androgen depletion/repletion might increase overall tumor cell kill. Feltquate et al. tested 4-week cycles (3 weeks of ADT, 1 of testosterone repletion) in patients with rising PSA or metastases. Seventeen of 27 evaluable patients achieved PSA declines for at least 6 cycles, and the proportion achieving undetectable PSA was similar to that previously observed with continuous ADT. This study provides the basis for further investigation of rapid androgen cycling in combination with other strategies to increase overall cell kill.
Soverini et al. Page 7374
ABL kinase domain mutations have been implicated in resistance to the BCR-ABL inhibitor imatinib mesylate in Philadelphia-positive (Ph+) leukemias. Soverini et al. analyzed ABL kinase domain sequences in the largest series of imatinib-resistant Ph+ patients reported so far, showing that a) mutations may account for or at least contribute to primary or acquired resistance to imatinib in approximately 40% of cases; b) the subsets of advanced phase chronic myeloid leukemia and Ph+ acute lymphoblastic leukemia patients are to be considered a high-risk group in terms of mutations development; and c) the occurrence of P-loop or T315I mutations in patients treated with imatinib are frequently associated with disease progression. Therefore, given that second-generation inhibitors are now available, there should be a rational reconsideration of the therapeutic strategy.