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View the Table of Contents for the January 1 issue of Cancer Research.
Page 22
Maroulakou et al. Page 167
The phosphatidylinositol-3-kinase Akt is causally linked to breast cancer and is a promising candidate for therapeutic intervention. Breast cancers which overexpress ErbB2 are associated with Akt pathway activation and poor prognosis. There are three isoforms of Akt and little is known of how they function. Maroulakou et al. used mammary gland–targeted expression of ErbB2 or PyMT to induce mammary adenocarcinomas and evaluated the role of each Akt isoform in null backgrounds. Ablation of Akt1 in these mice inhibited oncogenesis, by inhibiting cell proliferation and survival in vivo, while ablation of Akt2 accelerated tumor induction by both oncogenes. These findings will likely influence how Akt inhibitors will be used for the treatment of breast cancer.
Heath et al. Page 202
Multiple myeloma is a B-cell malignancy characterized by the uncontrolled growth of plasma cells in the bone marrow, and the development of osteolytic bone disease. Myeloma cells express the receptor activator of NFκ-B (RANKL), induce RANKL expression in the bone marrow, and down-regulate expression of the decoy receptor osteoprotegerin (OPG), thereby promoting bone resorption. Heath et al. investigated the ability of an OPG-like peptidomimetic (OP3-4), designed to block the RANKL/RANK interaction, to inhibit osteoclastic bone resorption and TRAIL-induced apoptosis in vitro and myeloma bone disease in vivo. This agent showed selective inhibition of RANKL, but not TRAIL activity, was effective in preventing bone disease associated with myeloma, and offers a novel therapeutic approach to treating this disease.
Many cervical cancers express the two human papilloma virus–derived oncoproteins E6 and E7. To explore the role of tumor-specific immunity to these antigens in cervical cancer progression, Piersma et al. analyzed the immune response at the local level and systemically by assessing the E6- and E7-specific T-cell response in the peripheral blood. Strong infiltration of the tumor tissue by CD8+ T-cells was associated with the absence of lymph node metastases. This effect was particularly evident in those patients displaying strong E6- and/or E7-specific T cell responses. This finding provides a powerful prognostic variable in cervical cancer patients.
Huffman et al. Page 417
The beneficial effects of calorie restriction have largely been attributed to an overall decrease in food intake, rather than overall body fat. To determine the role of obesity on cancer risk, Huffman et al. used temperature differences to modify energy expenditure and, hence, weight gain in the TRAMP model of prostate cancer predisposition in mice. It was found that despite a similar food intake, mice with greater body mass and fat stores had more advanced prostate cancer than leaner mice. Moreover, increasing food intake by nearly 30% without changing body composition did not affect cancer progression. These results suggest that excess calorie retention reflected in greater body mass, rather than consumption, confers cancer risk in this model.