Editors' ChoiceCancer

Tumor Imaging: Surgeons Can Have It All

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Science Translational Medicine  31 Mar 2010:
Vol. 2, Issue 25, pp. 25ec53
DOI: 10.1126/scitranslmed.3001101

When the British rock band Queen belted out “I Want It All,” they could have been recording an anthem for cancer surgeons. Indeed, complete removal of a tumor, with the absence of cancerous cells at the surgical margins, remains a cornerstone for the successful treatment of most solid-tumor malignancies. Positive margins, or the presence of tumor cells at the cut edge of the surgical specimen, have been associated with increased local recurrence and poorer prognosis in cancers of the head and neck, lung, breast, and colon. In attempts to verify clear margins during initial tumor resection, clinicians currently rely on immediate (frozen) evaluation of small tissue samples taken from the operative site. However, this process is time-consuming and labor-intensive, increases anesthetic risks, and occasionally leads to erroneous conclusions. Now, Nguyen et al. explore the use of activatable cell-penetrating peptides (ACPPs) to improve the visualization of tumor margins during surgery.

Using ACPPs carrying fluorescent labels, the researchers successfully delineated tumor margins in mouse models of melanoma, sarcoma, and breast cancer. The ACPPs contain short polycations attached via linkers to neutralizing polyanions. Matrix metalloproteinases, enzymes frequently expressed by tumors to facilitate local invasion and metastasis, cut the linker and release the polyanion. This cleavage allows the polycation, along with its fluorescent label, to adhere to and selectively enter tumor cells in the immediate vicinity. Surgery guided by ACPP labeling reduced residual tumor cells 10-fold and improved overall as well as tumor-free survival. Furthermore, these reagents can be used to facilitate visualization of residual tumor during postoperative magnetic resonance imaging, which allows for evaluation of the completeness of tumor removal in a noninvasive manner.

Compared with other targeted fluorescent probes previously described in the literature, the use of ACPPs as described by Nguyen et al. offers improved cancer-cell specificity while being applicable to a wide variety of tumor types. This technology thus holds great promise as a navigational tool for the surgical treatment of large and invasive tumors.

Q. T. Nguyen et al., Surgery with molecular fluorescence imaging using activatable cell-penetrating peptides decreases residual cancer and improves survival. Proc. Natl. Acad. Sci. U.S.A. 107, 4317–4322 (2010). [Abstract]

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