When testing patients for prostate cancer, clinicians arelooking for prostate specific antigen (PSA), a glycoprotein that is present insmall quantities in the serum of men with healthy prostates, but often elevatedin the presence of prostate cancer or other prostate disorders. If PSA levelsare abnormal, clinicians will check for cancer with an expensive—and sometimespainful—biopsy procedure. If the biopsy shows no cancer, but PSA levels remainhigh over time, the physician will repeat the biopsy at further expense andmore patient discomfort.
What's more, these tests are not precise enough, says Dr.Jennifer Linehan, a urologic oncologist at City of Hope who specializes inrobotic surgery, mostly for patients with kidney, bladder and prostate cancer.
"On the research side, I have been focusing ondifferentiating prostate cancer from benign prostate tissue, as well asdifferentiating prostate cancer from more aggressive cancers that are going todevelop faster, in an effort to achieve better outcomes for patients," saysLinehan, a surgical fellow in City of Hope's Division of Urology and UrologicOncology.
In 2006, the City of Hope team published a report in thejournal Nano Letter describing theiruse of a bacterial enzyme known as methyltransferase to attach as many as threedifferent targeting molecules to a piece of Y-shaped DNA. The researchersengineered the Y-shaped DNA so that it contains a specific nucleic acid, knownas 5-fluorocytosine, at the end of each arm. 5-Fluorocytosine tricks the enzymeinto forming a chemical bond between the enzyme itself and the DNA molecule.The researchers also created so-called "fusion" proteins betweenmethyltransferase and proteins, such as thioredoxin, that bind to malignantcells. The investigators then tested whether a nanoscale device could targetprostate cancer cells expressing the thioredoxin receptor on their surfaces anddistinguish among those cells and those not expressing this particularreceptor. Fluorescence imaging showed that this nanoscale construct did bindonly to those cells expressing the thioredoxin receptor, suggesting to theinvestigators that their nanoscale device could be useful in histological tumortyping assays.
Following up on these findings, Linehan and her colleaguespresented data at the American Urological Association's 2012 Annual Meeting inAtlanta comparing how the nanodevice binds to stromal tissue found in prostatecancers and tissue from benign prostatic hyperplasia. Using this nanodevice totest the stroma in a biopsy sample could make the first biopsy all that isnecessary, according to the researchers.
The study's sample size was relatively small, notes Linehan,but the results of this study are mighty. The research team collected frozentissue samples of prostates that were surgically removed from 45 patients, 18of which contained prostate cancer and 17 of which contained benign prostatichyperplasia. The samples were incubated with varying concentrations of thenanodevice, and then the intensity of their glow was measured.
"We had a small study sample and couldn't use all of thespecimens, but as far as how the device works, we established that very well,"says Linehan.
City of Hope's report has commercial opportunities beyondprostate cancer, Linehan notes. The methods the researchers developed can betailored to attach a different molecule to each arm of the Y-shaped DNAmolecule. In addition, because the scaffold designed by the researchers isreadily absorbed into cells, it can be used to deliver chemotherapeutic orother therapeutic agents, Linehan suggests.