A new sensor, found capable of identifying ovarian cancer in a noninvasive way in mice, may have the potential to detect early-stage ovarian cancer in the future, and possibly monitor for cancer recurrence.
The technology is based on the detection of human epididymis protein 4 (HE4), one of the biomarkers approved by the U.S. Food and Drug Administration for detecting high-grade serous ovarian carcinoma (HGSC), the most frequent type of ovarian cancer.
The study, “Noninvasive ovarian cancer biomarker detection via an optical nanosensor implant,” was published in the journal Science Advances.
Ovarian cancer is frequently associated with poor outcomes, in part due to the advanced stage at which most cases are detected — at stage 3 or later in more than 60 percent of diagnoses — higher than any other form of cancer.
The current screening methods, cancer antigen 125 testing and transvaginal ultrasounds, are not recommended by the U.S. Preventive Services Task Force because they don’t benefit patient outcomes nor do they reduce mortality rates.
Therefore, new methods to provide early-stage detection of ovarian cancer are needed.
While cancer cells produce high amounts of certain proteins like HEA, patients with early-stage cancer have very low levels in the blood, making it hard to diagnose the disease.
So researchers devised a new type of sensor to detect HEA closer to the site of tumor growth and with higher sensitivity.
The biomarker is increased in patients with HGSC, particularly in the uterine cavity, where it can reach levels 23-fold higher than in the blood.
The device is an optical sensor, consisting of a carbon nanotube linked with an anti-HE4 antibody. Normally when the nanotube is probed, it emits a red light, but in the presence of HE4 there’s a shift in light emission from red to blue. This shift can then be measured to assess the presence of HE4 and, as a result, cancer.
The sensor was tested in fluid samples from ovarian cancer patients, requiring very small amounts to do a measurement. Blood samples from patients with HGSC were clearly distinguished by the sensor from those collected from patients without cancer.
In addition, by using patient samples of ascites — fluid from the abdominal cavity — the nanosensor could also significantly separate samples from patients with HGSC.
Since the detector could distinguish benign from malignant HE4 concentrations, the results confirmed that it had the ability to identify patients with HGSC.
Researchers then engineered an implantable device incorporating the nanotube-antibody complex, and surgically implanted it into mice. The implant was then probed noninvasively from the outside, using a sensitive light detector.
Using four different mouse models of ovarian cancer, the device successfully distinguished animals with tumors producing high levels of HE4 compared to mice with tumors with very low levels of HE4. The sensor was able to detect ovarian cancer in vivo in these animals for at least 24 hours.
“We found that the sensor can quantify HE4 in patient serum and ascites samples at relevant biomarker concentrations, potentiating future use as a rapid or point-of-care sensor,” researchers wrote.
For potential clinical use in the future, several sites for implantation can be considered, including areas near the ovaries, fallopian tube, or within the uterine cavity, researchers said.
The device might be particularly helpful for early detection in women with an increased risk of ovarian cancer, such as those with a family history of ovarian or breast cancer; patients with BRCA1 or BRCA2 mutations; those who experiencing early menarche (first menstrual cycle), late menopause, or who have endometriosis.
In addition, patients treated for primary disease may also benefit from the sensor to monitor cancer recurrence.
“The stratification of patients to determine who may be good candidates will be important for the successful translation of this technology,” researchers wrote. “Future work will investigate several approaches to … improve sensitivity of both ex vivo measurements of patient biofluids and in vivo detection.”