Prof Lorraine O’Driscoll is looking for cancer-related molecular signals in the blood that could help predict how patients will respond to cancer treatment and to monitor their progress. She spoke to Claire O’Connell about the search for non-invasive biomarkers.
Imagine if you could predict how a patient is likely to respond to an anti-cancer drug simply by taking a sample of his or her blood. Then what if you could check the patient’s blood every so often to monitor how the cancer is responding to the treatment? Being able to capture information about cancer from the blood is far less invasive than finding and removing tumour tissue samples, but first we need to find robust signals in the blood that can tell tales on cancer elsewhere in the body.
Prof Lorraine O’Driscoll, associate professor of pharmacology and director of research at the School of Pharmacy and Pharmaceutical Sciences in Trinity College Dublin, is looking for these signals, or biomarkers, and one of her lab’s main interests is in breast cancer.
“We are particularly interested in minimally invasive biomarkers, the ones you can pick up in the blood,” she explains. “There are good tissue-based biomarkers that can tell you about the tumour, but to get those you have to know where the tumour or its metastases [‘secondaries’] are in order to take a needle biopsy, and that is much more invasive for ongoing monitoring of a patient during their treatment.”
Predicting response to treatment
O’Driscoll and her co-workers are looking for biomarkers in blood that can help predict whether breast cancer will respond to Herceptin and related drugs. While these drug treatments can be effective against breast cancers that over-express a molecule called the HER-2 receptor, not all cancers respond well to them, or some cancers that respond initially may develop resistance over time, explains O’Driscoll.
“We want to identify biomarkers to predict in advance the response to these drugs – that’s what is needed for patients to get on the right treatments,” she says. “Another benefit is that if we can predict the response to an individual cancer, healthcare systems would not be paying for these expensive drugs being used in patients who are not likely to benefit from them.”
To hunt for potentially useful biomarkers, O’Driscoll and colleagues analysed cancer cells growing in the lab and they also looked at archived samples from patients. Those studies, which were funded by the Health Research Board and Science Foundation Ireland (SFI), have identified several molecules in blood that seem to be linked to how breast cancers respond to treatment with Herceptin and related drugs, and now a selection of the candidate biomarkers are being investigated in studies with ICORG to hopefully bring them closer to the clinic.
Enter the exosome
O’Driscoll’s search for biomarkers has also opened up another interesting avenue. “When we were looking for these biomarkers in the blood, we were finding molecules that shouldn’t survive in blood. We figured the molecules had to be protected in some way, so we filtered the samples and looked under the electron microscope,” she says. “And what we saw was that the molecules were inside tiny, nanosized vesicles called exosomes.”
Exosomes are little membrane-bound packages that emerge out of the cancer cells and can travel in the blood, and they have been generating interest in recent years, not just about how they might be involved in the spread of cancer in the body but also how they might be used in diagnosis or even to deliver treatments.
“We think exosomes and their contents are probably involved in preparing the micro-environment at other sites for spread of cancers and they seem to be able to carry drug resistance genotypes with them – in lab experiments, exosomes from non-sensitive cells can make sensitive cells resistant,” explains O’Driscoll. “And because the molecules in these little vesicles are a micromap of their cell of origin, that’s why they could be useful as biomarkers, to tell you about the cancer they came from.”
O’Driscoll is chairing a European COST action to bring researchers in the field together and hammer out issues, such as nomenclature and guidelines for isolating and quantifying exosomes and similar structures called microvesicles. “I think their potential both as biomarkers and being able to target them before they leave the cancer cell is very important,” says O’Driscoll. “And in the future we may be able to take exosomes from a patient and use them as vehicles for delivering drugs, there are a lot of possibilities there.”
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