Zaver Bhujwalla, Ph.D.

Using advanced microscopes equipped with tissue-penetrating laser light, cancer imaging experts at Johns Hopkins have developed a promising new way to accurately analyze the distinctive patterns of ultra-thin collagen fibers in breast tumor tissue samples and to help tell if the cancer has spread.

The Johns Hopkins researchers say their crisscrossing optical images, made by shining a laser back and forth across a biopsied tissue sample a few millionths of a meter thick, can potentially be used with other tests to more accurately determine the need for lymph node biopsy and removal in women at risk of metastatic breast cancer.

In what is believed to be the first study to measure minute changes in tumor connective tissue fibers, researchers found that eight women whose cancers had spread beyond the breast through the body’s lymphatic system had about 10 percent more densely packed and radially spread-out collagenous structural proteins than six women whose cancers had not yet spread. Collagen fibers in the non-metastasized tumors, also obtained during breast biopsy, were more diffuse and arranged in a transverse or horizontal pattern. All
14 women in the study had aggressive, malignant breast cancer.

In the new report, to be published in the Journal of Biomedical Optics online Nov. 1, researchers say that if these “proof of principle” findings hold up in testing now under way in hundreds more women with or without metastatic breast cancer, then their new optical imaging tool could simplify testing for spreading disease and help people avoid unnecessary lymph node surgery.

Experimenting with human prostate cancer cells and mice, cancer imaging experts at Johns Hopkins say they have developed a method for finding and killing malignant cells while sparing healthy ones.

The method, called theranostic imaging, targets and tracks potent drug therapies directly and only to cancer cells. It relies on binding an originally inactive form of drug chemotherapy, with an enzyme, to specific proteins on tumor cell surfaces and detecting the drug’s absorption into the tumor.  The binding of the highly specific drug-protein complex, or nanoplex, to the cell surface allows it to get inside the cancerous cell, where the enzyme slowly activates the tumor-killing drug.

Researchers say their findings, published in the journal American Chemical Society Nano online Aug. 6, are believed to be the first to show that chemotherapies can be precisely controlled at the molecular level to maximize their effectiveness against tumors, while also minimizing their side effects.

Senior study investigator Zaver Bhujwalla, Ph.D., a professor at the Johns Hopkins University School of Medicine and its Kimmel Cancer Center, notes that a persistent problem with current chemotherapy is that it attacks all kinds of cells and tissues, not just cancerous ones.

A team of cancer imaging experts at Johns Hopkins has embarked on a five-year research initiative to speed development of early diagnostic tests and new treatments for breast, prostate and other common cancers.

Using advanced imaging tools developed or used for the last decade at Johns Hopkins In-Vivo Cellular and Molecular Imaging Center (ICMIC), the team will search for innovative ways to detect cancers in their earliest stages inside cells, and for ways to stop or kill any of these cancer cells before the disease can spread to other tissues and organs.

“Our next round of studies are aimed at turning what we’ve shown to be feasible into clinical reality,” says cancer imaging researcher Zaver Bhujwalla, Ph.D., who will act as the principal investigator of the expanded initiative.  The expansion is made possible with more than $8 million in new grants from the U.S. National Cancer Institute, a member of the National Institutes of Health.  “By harnessing the very latest technology in noninvasive imaging — using any single or combination imaging modality of MRI, CT, SPECT, PET, laser optics or ultrasound — we expect to develop tests that detect cancer faster and earlier, distinguish spreading or metastatic tumors from dormant ones, and develop better and more tolerable chemotherapy drugs that only attack cancerous cells, leaving healthy cells alone,” she adds.