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View the Table of Contents for the July 1 issue of Clinical Cancer Research.
Scott et al. Page 4810 Chong et al. Page 4818
The humanized monoclonal antibody huA33 targets the A33 antigen, which is expressed in colorectal cancer and in normal intestinal mucosa. Scott et al. conducted a Phase I biopsy-based trial 131I-huA33 to determine the targeting characteristics of this antibody. huA33 was well tolerated and demonstrated selective and rapid localization to colorectal carcinoma in vivo, with penetration to the center of large necrotic tumors. The colon elimination half-life of huA33 was equivalent to basal colonocyte turnover. Chong et al. conducted a second Phase I trial in 15 patients with metastatic colorectal carcinoma to evaluate escalation of 131I-humanized monoclonal antibody huA33 radioimmunotherapy. There were no acute infusion-related adverse events, and there was excellent tumor targeting of 131I-huA33 demonstrated in all patients up to six weeks post infusion. At restaging, 4 patients had stable disease, while 11 patients had progressive disease. 131I-huA33 shows promise in targeting colorectal tumors, and further studies of 131I-huA33 in combination with chemotherapy are planned.
De Laurentiis et al. Page 4741
Experimental data suggest a complex cross-talk between HER2 and the estrogen receptor (ER), and it has been hypothesized that HER2+ tumors may be less responsive to certain endocrine treatments. To study this issue in the clinical setting, De Laurentiis et al. have conducted a meta-analysis on the interaction between the response to endocrine treatment and the overexpression of HER2 in metastatic breast cancer. Twelve studies (N=2,379 patients) were included in the meta-analysis. Overall, a higher risk of endocrine treatment failure for HER2+ tumors has emerged, regardless of the type of endocrine agent and of the ER status. This supports a possible interaction between HER expression and endocrine treatment efficacy.
Opalinska et al. Page 4948
Silencing of either the Myb or Vav protooncogenes with antisense oligodeoxynucleotides (AS ODN) impairs leukemic cell growth. Since each gene sustains or stimulates leukemic cell growth through non-overlapping pathways, one could reasonably hypothesize that simultaneous inhibition of both genes might enhance the antileukemic effect of compounds employed to silence either one. This has now been shown to be the case, importantly in primary leukemic cells. The effectiveness of the dual targeting strategy suggests a new approach for increasing the therapeutic effectiveness of gene silencing strategies, with AS ODN, and likely for siRNA as well.
Ulfarsson et al. Page 4674
Craniopharyngioma is an intracranial tumor that is difficult to treat due to its location close to vulnerable structures. In a search for new therapeutic targets, Ulfarsson et al. explored the role of IGF-1 receptor in craniopharyngioma growth. Using low-passage craniopharyngioma cell lines from different patients, they demonstrated that more than half of the tumor cell lines exhibit strong expression of and dependence on IGF-1 receptor signaling. These data highlight the possibility of inhibiting the IGF-1 receptor as a therapeutic option for craniopharyngioma.
T. Curran Page 4644
There is growing interest and enthusiasm in translating basic research discoveries into cures for cancer. However, to be successful, many hurdles must be overcome at the interface of laboratory and clinic. Curran contends that translational research requires a fresh approach that acknowledges that many kinds of investigators contribute to the ultimate goal and that open communication and teamwork among all of these are essential. In addition, the research community must carefully select the people and projects for investment of the enormous resources required to avoid the futility of attacking the wrong target.