Researchers at Barts Cancer Institute, Queen Mary University of London have developed a testing regimen using circulating tumor cells (CTCs) found in a patient’s blood that can identify resistance to the common cancer treatment docetaxel for prostate cancer. The findings, presented at the NCRI Festival, could pave the way for a non-invasive procedure to detect resistance early and switch patients to alternative therapies such as abiraterone or cabazitaxel.
The team, led by Ph.D. research candidate Caitlin Davies, collected blood samples over about eight months from 56 patients being treated for prostate cancer at Barts. Samples were collected prior to the start of docetaxel treatments, after the first dose of chemotherapy, before the fifth dose, and once the patient had finished all doses.
By collecting patients’ samples over the course of their treatment, the investigators were able to monitor changes in CTCs to show each patient’s response to the treatment. “We then looked for patterns in the data from men who responded or did not, or whose disease progressed sooner than others after treatment,” Davies noted.
“Using these patterns, we can apply them to future patients with the goal to predict whether they will respond to therapy and preemptively decide on the best course of action that will have maximal benefit. For instance, an increase in CTC numbers may indicate a lack of response to treatment. Furthermore, by monitoring the appearance of potentially drug-resistant CTCs, we can change treatment tactics early on and in a patient-personalized and timely manner.”
Among the patients less likely to respond to docetaxel, their cancer was more likely to recur or progress within three months and—notably— if more than six CTCs per 7.5mL of blood were detected before a patient’s first docetaxel dose, they were more likely to die within 18 months. This compared to progression-free survival of 17 months and an overall survival time of three years for men with fewer than six CTCs detected per 7.5mL of blood.
Among the several subtypes of CTCs the researchers were able to identify, they found that having more than one ‘classic’ type of CTC (epithelial, cytokeratin positive cells or E-CTCs) before docetaxel treatment predicted that the disease would progress within two months following treatment, instead of more than a year later. It also predicted survival: nine months versus 32 months for those without E-CTCs.
Further, higher CTC counts detected towards the end of treatment predicted a shorter time to disease progression and death. The disease was also eight times more likely to progress within six months in patients who showed an increase in CTCs without epithelial features than in those who did not have an increase.
“This insight into how CTC dynamics lead to reduced progression-free and survival times is vital for clinicians. It will enable them to make early changes of treatment from docetaxel to an alternative, which may significantly improve patients’ chances of long-term survival,” said Davies.
While the results of this research is promising, the team will move to next steps, including validating the results in a larger patient cohort. As part of their ongoing research, the Barts group is investigating a number of genes in CTCs that may be involved in resistance to docetaxel in order to understand the mechanisms and identify new targets for anti-cancer drugs.