Editors' ChoiceProstate Cancer

Ironing Out MYC in Prostate Cancer

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Science Translational Medicine  17 Oct 2012:
Vol. 4, Issue 156, pp. 156ec188
DOI: 10.1126/scitranslmed.3005118

Myc is a growth-promoting protein implicated in the formation of several malignancies, including prostate cancer. Activation of Myc has numerous effects within a cell, including increasing expression of the transferrin receptor 1 (TFRC). As the name implies, the TFRC binds transferrin, a protein that is found in the blood and helps regulate iron transportation and homeostasis. Numerous cancers express TFRC on the cell surface, and many investigators have attempted to target TFRC as a mechanism for imaging tumor cells. Until now, many of these approaches have been plagued by high rates of background signal generated by nonspecific uptake of the imaging agents.

Holland and colleagues tackled this challenge by using a novel tracer to test whether TFRC could act like a dock to bind radioactively labeled transferrin. They chose 89Zr as the radionuclide because it produces strong, quantitative signals when imaged with a positron emission tomography (PET) scanner and has a long half-life of 78.4 hours. To generate the tracer, the group first coupled the iron chelating agent desferrioxamine B (DFO) to transferrin and then linked it to 89Zr. They then injected the 89Zr-DFO–labeled transferrin tracer into mice harboring subcutaneous tumors or spontaneous prostate cancers expressing Myc and found that both mouse models demonstrated significant uptake and retention of the tracer within the tumors. With PET imaging, the authors were able to detect the tumors within hours of injecting the tracer.

Because existing imaging modalities are readily able to detect invasive prostate cancer, Holland et al. proceeded to test whether the earliest precursor to prostate cancer, prostatic intraepithelial neoplasia (PIN), could also be visualized with 89Zr-DFO–labeled transferrin. In transgenic mice that always develop prostate cancer, the authors detected PIN lesions via PET imaging even before enlargement of the prostate had occurred.

These results have potential implications for understanding multiple tumor types, including prostate cancer, in which TFRC expression is elevated. In the tumors tested in this study, the rise in TFRC was driven by Myc activation, suggesting that the effects of important cancer pathways can be noninvasively tracked by monitoring downstream reporters, such as TFRC. However, the clinical utility of this approach will need to be tested with carefully conducted human studies.

J. P. Holland et al., Annotating MYC status with 89Zr-transferrin imaging. Nat. Med. 18, 1586–1592 (2012). [PubMed]

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