Applications

Circulating tumor cells (CTCs) have a huge potential to influence the treatment and prognosis for patients with cancer. However, the only tool available on the market, CellSearch, shows variability in the results while tested on positive samples. This fact prevents its clinical implementation for routine CTC detection. Also, CellSearch is primarily based on the detection of epithelial markers. However, when cancer cells undergo the Epithelial-mesenchymal transition at the initiation of metastasis, these markers disappear from the CTCs surface. Therefore, CTCs become undetectable using this technique.

Hence, our goal is to develop an economic and sensitive assay for CTC detection, that does not depend on those markers. We based our system on the detection of two markers specific to cancer cells: Increased lactate production is a differentiating feature of many cancer cells compared to normal cells (Warburg effect). As the second signal we chose the sensitivity to TRAIL-induced apoptosis. The combination of these two signals is necessary to make our test more specific.

Figure 1. Scheme representing the current state of art and where MicroBeacon will intervene.

Application and Clinical setup

Regarding the positioning of our system in the chain of cancer treatment and diagnosis, we see our test as a new standard routine test which is applied regularly upon diagnosis of localized cancer to anticipate occurrence of metastasis, or upon successful treatment of initial cancer. We find the latter of these options to be very important, since currently the danger of remission is very high and its detection is only possible 3 to 4 years after the initial cure, at a time when it is often too late. This is due to the fact that imaging techniques such as CT scans can only detect metastasis when the upcoming tumor is already of considerable size [Paik et al, 2000]. Detection of metastasis in early stages, meaning the time when CTCs are present in the blood of patients, comprises a big advantage and opportunity for effective and comparably light treatments.

Our system is designed for use in any kind of laboratory which has access to the necessary hardware, which we are trying to minimize. A blood sample will be retrieved from patients, cleared of red blood cells, and incubated with sTRAIL (see Figure 2). In a second step, the sample will be introduced into a simple microfluidics chip, where our MicroBeacon bacteria will detect apoptotic, lactate producing cancer cells (see our System Overview for more details). As a next step, we are planning to establish a system to extract the positive cells from the chip and analyze them more closely to decide on further treatment protocols.

Figure 2. Scheme representing the handling of our MicroBeacons for cancer detection.