Magic wands and other innovations to find cancer
UC Davis Cancer Center’s Biomedical Technology Program developing light-based technologies
Building technologies to better detect and treat cancer
If you had a wand that could distinguish cancer cells from normal cells with just a beam of light, where would you use it first?
Laura Marcu, a UC Davis professor of biomedical engineering and neurological surgery, would use it on brain tumors. Marcu is program leader of the UC Davis Comprehensive Cancer Center’s Biomedical Technology Program, which is engineering new devices to aid in the detection and treatment of cancer.
Marcu has such a wand: a hand-held probe connected to a laser that shines light onto human tissue, and a detector that can read the fluorescence emission light generated by the molecules in the illuminated tissue area. The reading should differ depending on whether the light shines on normal, healthy tissue or cancerous tissue.
The wand is a centerpiece of the Biomedical Technology Program, which has a team of researchers, more than 20 active projects and almost $24 million in funding. These projects also include the development of molecular-targeted nano-probes that might help in imaging cancer.
Marcu, who came to UC Davis via the University of Southern California and Cedars-Sinai Medical Center in Los Angeles, explains that she developed the wand for brain tumors, medically known as gliomas, because the prognosis for brain tumors is very poor and because preserving healthy brain tissue during tumor removal is so crucial.
Patients with cancer usually undergo chemotherapy and/or radiation treatment. But surgery is generally the most effective method of killing cancer. A patient’s prognosis typically depends on how much of the tumor can be removed surgically. That is particularly true with brain cancers, which are not effectively responsive to chemotherapy and radiation, Marcu says.
The trouble with brain tumors is that they can grow like trees, with branches snaking out into the normal tissue. That is partly why only 25 percent of people diagnosed with gliomas survive two or more years.
That means the tumor does not have defined margins that can be easily detected by conventional imaging techniques such as magnetic resonance imaging (MRI) or computer tomography (CT) scans that are typically taken prior to surgery. During the operation, the surgeon removing a glioma must be able to distinguish normal tissue from cancerous tissue, and that is the challenge. Surgeons do not want to leave tumor cells, but they also do not want to cut out normal tissue and leave the patient with a serious neurological deficit.
Currently, surgeons take a small piece or “biopsy” of tissue from what they think is the edge of the tumor and freeze it so that it can be mounted onto a glass slide. A neuropathologist looks at the slide under a microscope to determine whether any cancer cells are left in that slice. If there are none, the surgeon assumes the entire malignancy has been removed and completes the operation. If the pathologist finds cancer cells, the surgeon removes additional tissue and the process is repeated.
But this process takes about an hour and requires a pathologist and other technicians to be on site throughout. In addition, only a small number of biopsies can be taken during surgery, making it less likely that the tumor's entire margin will be evaluated.
Marcu’s technology would do the job instantaneously – literally at the speed of light, allowing for multiple “optical biopsies” that do not require tissue removal for evaluation.
The technology takes advantage of the fact that when the brief pulses of laser light are directed onto cells, molecules in the cells absorb the energy. Then they re-emit the energy back in a form of fluorescence emission light. But different molecules re-emit light in slightly different wavelengths and for different amounts of time. That means different cells – like cancer cells – will emit their own profile of light.
With hundreds and even thousands of protein and metabolite molecules absorbing and emitting light, it is a daunting prospect to resolve the fluorescence emission in a way that allows recognition of cancer cells.
But Marcu believes she has worked it out. In a 2004 article, Marcu wrote that cancer cells emitted light with more intensity and for specific amounts of time at certain wavelengths, allowing for the discrimination of cancerous tissue from normal tissue. Neurosurgeons are testing the technology with actual patients. The first prototype device developed in her laboratory has been used in about 60 patients, including some at Cedars-Sinai Medical Center, where Marcu worked before joining UC Davis. Marcu says the device needs to be used on more than 200 patients to definitively demonstrate that it makes a substantial difference.
So far, the results are promising, Marcu says. Early evidence suggests that in 95 out of 100 times the probe detects low-grade glioma cancer cells when they have been left behind.
More recently, using more advanced prototype devices developed at UC Davis, Marcu has begun a clinical trial in collaboration with neurosurgeon James E. Boggan. Her new devices also are tested for the diagnosis of other cancers. She now works with head and neck surgeon D. Gregory Farwell to determine the applicability of her technology for diagnosis of oral cancers during surgery.
And that could save a lot of lives.