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View the Table of Contents for the November 1 issue of Clinical Cancer Research.
Brown et al. Page 6480
There are concerns over the late effects of cancer therapy, including accelerated bone loss leading to increased risk of osteoporosis, but there has been little evaluation of the skeletal effects of chemotherapy alone in adults, especially in men. Brown et al. have shown that in long-term survivors of testicular cancer and lymphoma, there is no difference in bone-mineral density between those who received chemotherapy and a cancer control group at either the spine or hip. The data show, reassuringly, that standard-dose cytotoxic chemotherapy has no lasting, clinically important, direct effects on bone metabolism in this patient group.
Nam et al. Page 6452
The KLK2 gene is a prostate-specific gene and is associated with prostate cancer risk. To examine the significance of KLK2 SNPs, Nam et al. sequenced the KLK2 gene among 20 prostate cancer patients and identified five single nucleotide polymorphisms (SNPs), which were then genotyped among 1,251 men who underwent prostate biopsy. Haplotype analysis showed that patients with the variant alleles (ACCTT) had a significantly high risk for having prostate cancer. This haplotype was also significantly associated with high serum levels of the KLK2 gene product, hK2, a prostate cancer tumor marker. These findings suggest a role for the KLK2 gene in prostate cancer susceptibility through induction of increases in hK2 production.
Balak et al. Page 6494
Lung adenocarcinomas that harbor epidermal growth factor receptor (EGFR) kinase domain mutations often respond to the tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib, but eventually become resistant because of a second-site EGFR mutation (T790M). To elucidate the frequency and nature of secondary EGFR mutations, Balak et al. examined tumor cells from 16 patients with acquired resistance. Molecular analyses revealed a novel D761Y mutation and common T790M mutations. Their data also suggest that the type and nature of kinase inhibitor resistance mutations may be influenced by both anatomical site and mode of binding to the kinase target.
Budd et al. Page 6403
Circulating tumor cells (CTCs) can be detected in some patients with metastatic breast cancer, and patients with >5 CTCs/7.5 mL of blood, whether determined prior to or during therapy, have a worse outcome than patients with fewer or no CTCs detectable. Budd et al. have compared the prognostic significance of the CTC assay, performed approximately 4 weeks following the initiation of a new line of therapy, with that of radiographic response using the WHO criteria in patients with metastatic breast cancer. Assessment of CTCs was found to be an earlier, more reproducible indication of disease status than were standard imaging methods.