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View the Table of Contents for the March 1 issue of Cancer Research.
Page 1893
Gupta et al. Page 2062
Ovariectomy prevents the formation of both estrogen receptor (ER)–positive as well as ER-negative breast cancers, suggesting that even ER-negative breast cancers are dependent on ovarian hormones for their formation. Gupta et al. hypothesized that steroid hormones promote the outgrowth of ER-negative cancers by influencing host cell types distinct from the mammary epithelial cells. Increasing the levels of circulating estrogens sufficed to promote the formation and progression of ER-negative cancers, which was accompanied by a systemic increase in host angiogenesis and was attendant with the recruitment of bone marrow–derived stromal cells. Furthermore, bone marrow cells from estrogen-treated mice were sufficient to promote tumor growth. These results revealed a novel mechanism by which estrogens promote the growth of ER-negative cancers.
Orlova et al. Page 2178
Molecular imaging of drug targets and biomarkers may facilitate the development and clinical use of individualized treatments using targeted therapeutics. The time to take a novel imaging agent from research to clinic can be reduced by avoiding complex biological production issues. Orlova et al. solved this issue by using peptide synthesis of Affibody molecules targeting the HER2 receptor to obtain a preparation suitable for radiolabeling at the clinic. Preclinical characterization showed specific tumor targeting, rapid biodistribution kinetics and blood clearance, and high-contrast gamma camera imaging 1 hour after injection. In patients, this radiopharmaceutical holds promise not only to localize tumors, but also to characterize them as HER2-positive, which then can influence treatment regimes.
In the context of pancreatic cancer, metastasis remains the most critical determinant of resectability and, hence, survival. The objective of this study was to determine whether Hedgehog signaling plays a role in pancreatic invasion and metastasis, as this likely will have profound clinical implications. Feldmann et al. confirmed pharmacologic Hedgehog pathway inhibition as a valid therapeutic strategy for pancreatic cancer, and demonstrated for the first time its particular efficacy against metastatic spread. By targeting specific cellular subpopulations likely involved in tumor initiation at metastatic sites, Hedgehog inhibitors may provide a new paradigm for therapy of disseminated malignancies, particularly when used in combination with conventional antimetabolites that reduce “bulk” tumor size.
Huang et al. Page 2226
Dasatinib is a novel kinase inhibitor recently approved for use in chronic myeloid leukemia, though its utility in solid tumors has only begun to be explored. To aid in clinical development, Huang et al. identified candidate molecular markers predictive of response to dasatinib in vitro and further assessed their predictive utility in additional cell lines. Most strikingly, the subgroup of breast tumors predicted to respond to dasatinib are “triple-negative” (ER–, PR–, and HER2–), suggesting that dasatinib may represent a valuable treatment option in this difficult-to-treat population. Clinical studies are now underway to determine the activity of dasatinib in these patients.