A new study led by WEHI researchers has developed a blood test capable of detecting drug resistance in ovarian cancer patients with BRCA1 mutations undergoing PARPi therapy. This breakthrough addresses a significant challenge in cancer treatment, as most patients eventually experience relapse due to drug resistance.
The research, led by Dr. Ksenija Nesic, solves a long-standing "blind spot" in cancer research by identifying DNA changes that cause splicing, a process where cancer cells with mutations in genes like BRCA1 become resistant to PARPi treatment. Splicing allows cancer cells to 'skip over' the mutation targeted by the drug, effectively removing the drug's vulnerability and causing resistance.
Detecting Resistance Through Blood Tests
The study demonstrates, for the first time, that this form of drug resistance can be detected in a subset of ovarian cancer patients through a blood test or by examining the patient's tumor. Specifically, the research identified this drug resistance in ovarian cancer patients who have mutations in the BRCA1 gene.
"This could be transformative for the cohort of ovarian cancer patients who have mutations in the BRCA1 gene, and potentially for other ovarian cancer patients too," said Dr. Nesic. "We are hopeful that further research will reveal similar splicing mechanisms in BRCA2 and other genes that relate to HRD."
Clinical Implications and Future Directions
Homologous recombination deficiency (HRD) is found in approximately 50% of ovarian cancer patients, with about half of these patients having mutations in the BRCA1 or BRCA2 genes. The new test offers a way to monitor for drug resistance, allowing clinicians to detect altered splicing of genes for BRCA1 and potentially other genes involved in HRD as their patient stops responding to therapy.
"The discovery is profound because it opens up an avenue to monitor for drug resistance, where clinicians can in the future easily detect altered splicing of genes for BRCA1 and potentially for other genes involved in HRD, as their patient stops responding to therapy," Dr. Nesic explained.
By identifying patients who are no longer responding to PARPi treatment early, clinicians can make better decisions and transition patients to the next best therapy. The ultimate goal is to stop drug resistance in its tracks, not only for PARPi but also for other types of drug resistance.
