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Selected Articles from the December 1, 2006 Issue
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View the Table of Contents for the December 1 issue of Clinical Cancer Research.
Shanley et al.
Page 7025
Shanley et al. report the first substantial clinical study of breast radiotherapy toxicity in BRCA1 and BRCA2 mutation carriers in the United Kingdom. The findings add substantially to the body of evidence from North America and Canada in which late toxicities have been found to be comparable between BRCA mutation carriers and women with sporadic disease. The report is published in combination with another paper by Shanley et al. in this issue describing a novel study of chemotoxicity in BRCA1/2 mutation carriers. These data support giving standard (as opposed to reduced) doses of chemotherapy to these patients in whom theoretical concerns have been raised about heightened toxicity due to inherited faults in DNA repair.
Perez et al.
Page 7079
S- and G2-cell cycle arrest allows for repair of potentially lethal DNA damage prior to mitosis. UCN-01, a Chk1 inhibitor, abrogates S- and G2 arrest and enhances cancer cell killing by DNA-damaging drugs in vitro. Perez et al. found that UCN-01 at 75% of its minimum tolerated dose was well-tolerated together with cisplatin. At this dose, concentrations of UCN-01 sufficient to modulate cell cycle progression were achieved. Immunohistochemistry for geminin (a biomarker for cell cycle progression) suggests that sufficient UCN-01 is bioavailable to modulate cell cycle in human tumor biopsies at this dose. Thus, the data provide a basis for more rational use of UCN-01 in combination with DNA-damaging drugs, facilitating further development of a potentially promising therapeutic strategy.
Schrohl et al.
Page 7054
Because only 50% of metastatic breast cancer patients benefit from cytotoxic chemotherapy, there is a need to develop validated markers to predict chemotherapy sensitivity/resistance in this patient group. Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been shown to protect against apoptosis. Schrohl et al. found that in a multivariate model including lymph node status, steroid hormone receptor status, menopausal status, dominant metastases site, type of chemotherapy, and disease-free interval, TIMP-1 was significantly associated with resistance to treatment. At a specificity of 100% the sensitivity was approximately 17%, suggesting that without misclassifying any responders, we could identify a group of nonresponding patients with metastatic breast cancer having no chance of responding to chemotherapy.
Zhou et al.
Page 7187
Second hand smoke (SHS) exposure is associated with higher risk of lung cancer, while its role in lung cancer survival is not clear. Zhou et al. examined the association between self-reported SHS exposure before diagnosis and overall survival in 393 early stage, non-small cell lung cancer patients. They found that SHS exposure is associated with worse survival for the highest versus lowest quartile of SHS exposure durations, especially for exposure at workplaces. The results support the importance of banning smoking in public and in workplaces.