PDF Version for Printing
The articles referenced in this Highlights section will be available online in HTML and PDF formats to all interested users at no charge until the next issue of Clinical Cancer Research is published. Click on the article title to view the complete article.
View the Table of Contents for the October 1 issue of Clinical Cancer Research.
Yang et al. Page 5817
Binding of cisplatin to nuclear DNA is believed to create the molecular lesions that trigger apoptosis, but the mechanism linking nuclear DNA adduct formation and cell death is unclear. In this study, Yang et al. define separately the sequelae of cisplatin interactions with nuclear DNA and with mitochondria in head and neck squamous cell carcinoma cell lines. The authors suggest that cisplatin can induce apoptosis in head and neck tumor cells by direct interaction with mitochondria. Cisplatin binding to nuclear DNA, long thought to be the cytotoxic lesion for this drug, may not be necessary to induce apoptosis.
Banach-Petrosky et al.et al. Page 5895
Epidemiological studies have shown that reduced levels of vitamin D represent a major risk factor for prostate cancer. Banach-Petrosky et al. investigated the relevance of Vitamin D3 for prostate cancer prevention using an autochronous mutant mouse model and found that Vitamin D3 is more effective for inhibition of prostatic intraepithelial neoplasia and/or cancer phenotypes if provided before their initial formation. This study may explain why Vitamin D has not been effective in many clinical trials that were focused on patients with advanced prostate cancer, and it suggests that delivery of Vitamin D to patients with prostatic intraepithelial neoplasia or to individuals at risk but with no overt histological changes would be more effective.
Balic et al. Page 5615
Disseminated tumor cells in the bone marrow of breast cancer patients are independent prognostic factors, but their biological potential is as yet unexplored. For example, it is unclear whether or not disseminated tumor cells are capable of forming metastases, a property ascribed to cancer stem cells. Balic et al. uncovered the presence of cancer stem cells in bone marrow disseminated tumor cells from 50 early-stage breast cancer patients. Thus, a high proportion of disseminated tumor cells exists in bone marrow and may be capable of forming metastases.
Grover et al. Page 5801
Immunization with dendritic cells represents a promising approach for generating T cell-mediated antitumor immune responses in cancer patients. In a clinical trial designed to augment vaccination efficacy and antitumor immunity, Grover et al. took the approach of infusing tumor antigen-pulsed dendritic cells directly into the peripheral lymphatics of melanoma patients. Unexpectedly, a majority of the patients developed rashes in sun-exposed areas of skin following immunization. In contrast to peripheral blood lymphocytes, T cells expanded from the rash biopsies contained very high frequencies of tumor antigen-specific, vaccine-induced T cells. These results demonstrate how immunization route and tissue inflammation significantly influence the in vivo homing characteristics of primed T lymphocytes.
Hidalgo et al. Page 5755
There are very few preclinical models of pancreatic cancer. Hidalgo et al. transplanted tumor material from patients' resection specimens into nude mice and found that tumors developed that could be serially passaged and retain the fundamental features of the original human tumor. This model has at least three potential applications: (1) screening new drugs against pancreatic cancer, (2) selecting the most active agent for an individual to personalize treatment, and (3) generating an expandable database of determinants of drug response.
Bosch et al. Page 5786
Despite the extensive clinical experience with docetaxel, unpredictable interindividual variability in efficacy and toxicity remains an important limitation. Large interindividual pharmacokinetic variability has been associated with variation in toxicity. Bosch et al. describe the influence of polymorphisms in the CYP3A and MDR1 genes on population pharmacokinetics of docetaxel. They found that a polymorphism [C1236T] in the MDR1 gene was significantly related to docetaxel clearance. This finding may provide a meaningful tool to explain interindividual differences in docetaxel treatment in daily practice.