A research team from the University of California Davis Comprehensive Cancer Center and The Jackson Laboratory (both CA, USA) has published the first proof-of-concept study demonstrating a novel method of personalizing treatments for aggressive bladder cancer in the journal PLoS One. This method of ‘prescreening’ could ensure that there is an increased chance that the patient will benefit from treatment. Overall, it could reduce toxicity, increase therapeutic efficiency and lower costs.
Current research can identify the mutations within a specific cancer, which clinicians can match targeted treatment to, however difficulties reside in identifying the genetic drivers. This means that oncologists may choose therapies that are often not optimal for the patient, and toxicities may arise.
Ralph de Vere White, Director of the UC Davis Comprehensive Cancer Center commented: “The patient gets a biopsy and we send the tissue off for genomic analysis, which will show us abnormalities that can be treated. Let’s say there are four of them. Now we have to guess which one is driving the cancer, and the success rate is about 12%. That’s putting the patient through a lot for just 12%.”
Within the study, bladder tumors were taken from individual patients and specific mutations were identified. The tumors were then grafted onto mice to create models that the researchers could then test multiple drugs on. If the therapies were effective in the mouse model, they could be given to the patient.
The mouse grafts exhibited 92–97% genetic fidelity to the original patient tumors, for a period of several months. Researchers have therefore hypothesized that the method could be more effective than using cell lines, which adapt genetically from the mother tumor after just a few days.
Most significantly, the grafts provided an insight into which drugs could be most effective for individual patients. The researchers were able to quickly determine which therapies were most beneficial, since tumors develop more rapidly in mice than in humans. Multiple biopsies were also conducted to investigate tumor evolution, escape mutations and test important therapeutic countermoves.
Chong-Xian Pan, first author and genitourinary oncologist at UC Davis Comprehensive Cancer Center commented: “In one case, the drug cisplatin didn’t work and gemcitabine barely worked, but the combination really knocked the tumor out in the mouse, and that’s exactly what happened in the patient.”
The team’s ultimate goal for the future is to use computers to identify effective personalized treatments from biopsies. In the meantime, the novel mouse model shows promise for cancer patients, while a high failure rate remains with standard of care.
Sources: Pan CX, Zhang H, Tepper CG et al. Development and characterization of bladder cancer patient-derived xenografts for molecularly guided targeted therapy. PLOS ONE DOI: 10.1371/journal.pone.0134346 (2015); UC Davis Comprehensive Cancer Center press release