SAN DIEGO—Biotech company Epic Sciences’ focus on circulating tumor cells (CTCs) will not only advance the clinical use of liquid biopsies and improve how metastatic cancer is treated, it says, but also identified a unique CTC biomarker in patients with metastatic prostate cancer who respond to PARP inhibitors cancer drugs in development.
In this vein, Epic had two major announcements on Nov. 16, the first of which was regarding a study published in PLOS ONE on new technologies to sequence the DNA of individual CTCs in order to understand tumor heterogeneity.
Epic says of this study that its single-cell genetic analysis has confirmed that cells within the same tumor can harbor different cancer-causing mutations. This tumor heterogeneity is believed to be responsible for how a cancer responds to therapy and eventually develops resistance and metastasizes, the company says, adding that tumor heterogeneity is now seen as one the greatest obstacles to treating metastatic cancer.
In other news released that same day, Epic Sciences announced the identification of a unique CTC biomarker in patients with metastatic prostate cancer who responded to PARP inhibitors, drugs which target cancer cells that have a type of genomic instability called homologous recombination deficiencies (HRD), which occurs when DNA repair genes, such as BRCA1 and BRCA2, are inactivated.
Traditionally, testing for HRD has been dependent on tissue biopsies, which are impractical and unreliable in metastatic cancer, according to various researchers. However, a liquid biopsy test could provide more accurate, faster results.
Epic Sciences says it has demonstrated a CTC biomarker that can identify patients with metastatic castrate resistant prostate cancer (mCRPC) who are more likely to respond to treatment with a PARP inhibitor in combination with androgen receptor signaling inhibitors (ARSi) compared to those treated with ARSi alone (overall response rate of 93 percent vs. 22 percent).
“PARP inhibitors are efficacious in a subset of patients with mCRPC, so it is critically important to find the patients who will benefit from these novel therapeutics,” states Dr. Felix Feng, associate professor of radiation oncology, urology and medicine at the University of California, San Francisco, and lead author of the study. “Identifying these patients with a simple blood draw represents a tremendous leap forward in the clinical development of PARP inhibitors.”
The biomarker was also used to observe and track dynamic changes in the HRD+ CTCs throughout a patient’s treatment. On average, patients receiving the PARP inhibitor in conjunction with ARSi saw a reduction of HRD+ CTCs during therapy, whereas on average, patients given the ARSi alone saw an increase of HRD+ CTCs while on therapy.
“This circulating tumor cell biomarker clearly distinguishes a subset of patients who will have poor clinical response on ARSi alone, but will have significantly improved responses with PARP inhibition. The biomarker’s higher prevalence has been confirmed in multiple independent cohorts,” states Ryan Dittamore, vice president of translational research and clinical affairs at Epic Sciences and co-author on the study.
“We are rapidly accelerating clinical development in partnership with biopharmaceutical companies and academic sponsors to evaluate the biomarker with many novel therapies, including PARP inhibitors and other novel HRD-targeting therapies across a range of cancers,” Dittamore adds. “[One] of the largest challenges in obtaining the approval and clinical adoption of PARP inhibitors is selecting the patients who will benefit from the therapy. More clinical development is required prior to these drugs being available, and we believe that Epic Sciences will play a major role in helping to identify patients who will have maximal benefit of PARP inhibitors.”
Commenting on the tumor heterogeneity issue, he said, “We found that CTCs in the same blood sample varied based on phenotypic differences (i.e. morphology or how they looked and what proteins they expressed),” Dittamore says. “This observation lead to our pursuit of single CTC sequencing to confirm the heterogeneity observed.”
To truly study tumor heterogeneity, “we knew we could not pool the cells and average the genetic mutations, similar to how tissue or cfDNA analysis provides an average of genomic alterations,” Dittamore explains. “So we developed analytic techniques and analytically validated a single circulating tumor cell sequencing platform, which enables us to understand tumor heterogeneity from a liquid biopsy, obtain the genomic drivers of disease progression, understand how genomic alterations are clustering together (which can allow further insights into the sensitivities and resistances to systemic therapies) and measure single cells for genomic/chromosomal instability.”