Biomarker Associated With Longer Survival Uncovered in Ovarian Cancer

Article

A new proteomic analysis found that CT45 is an independent prognostic factor in patients with high-grade serous ovarian cancer, and a potential target of immunotherapies.

A new proteomic analysis found that cancer/testis antigen 45 (CT45) is an independent prognostic factor in patients with high-grade serous ovarian cancer (HGSOC), and a potential target of immunotherapeutics. Patients with higher levels of CT45 had substantially better disease-free survival (DFS).

Standard treatment for HGSOC includes surgery and carboplatin/paclitaxel chemotherapy, and 80% of patients experience intra-abdominal recurrence requiring subsequent rounds of chemotherapy. “However, one in six patients remains disease free for more than 10 years after an initial diagnosis of advanced-stage metastatic disease,” wrote study authors led by Fabian Coscia, PhD, of the Max Planck Institute of Biochemistry in Martinsried, Germany. “At present, no known molecular mechanisms are associated with this prolonged survival, and no good predictor markers exist to distinguish these patients from others with HGSOC who do poorly.”

The investigators conducted a proteomic analysis of paraffin-embedded patient samples, including 11 HGSOC patients who were chemoresistant (median DFS, 190 days) and 14 patients who were chemosensitive (median DFS, 1,160 days). The results of this analysis were published in Cell.

From an overall collection of more than 9,000 proteins, the researchers identified CT45 as a significant variable between the groups. Patients with high CT45 expression (top quartile) had a median DFS of 2,754 days, compared with a median of 366 days for all other patients (P = .008). Overall survival was also significantly better, at 2,903 days compared with 1,078 days (P = .016).

They confirmed the finding in a separate set of more than 200 cases of primary and metastatic epithelial ovarian cancer. In that cohort, CT45 expression was correlated with chemosensitivity in 124 patients with advanced-stage disease (P = .005). In 42 patients with high CT45 expression, DFS was prolonged compared with those with no expression (363 days vs 153.5 days; P = .02). One further cohort of 284 HGSOC patients from the Cancer Genome Atlas again confirmed the finding.

The investigators found that CT45 is connected to DNA damage pathways via interaction with the PP4 phosphatase complex. “We suspect that CT45 plays a major role in the response of tumors to carboplatin,” said Marion Curtis, PhD, a co-author at the University of Chicago, in a press release. “This gives us hope that future strategies that activate CT45 expression in the tumor could make it more sensitive to carboplatin treatment.”

The authors wrote that there could be significant clinical implications to these findings, given the apparent connection between CT45 and long-term survival. “A treatment strategy in which CT45 expression is reactivated using demethylating agents, which are in clinical trials, may be effective against tumors lacking CT45,” they wrote. “Based on our results, expression of CT45 is expected to improve the efficacy of platinum-based chemotherapy or immunotherapy for patients with advanced-stage ovarian cancer.”

Related Videos
Brian Slomovitz, MD, MS, FACOG discusses the use of new antibody drug conjugates for treating patients with various gynecologic cancers.
Developing novel regimens may continue to improve survival outcomes of patients with advanced cervical cancer following the FDA approval of pembrolizumab and chemoradiation, says Jyoti S. Mayadev, MD.
Treatment with pembrolizumab plus chemoradiation appears to be well tolerated with no detriment to quality of life among those with advanced cervical cancer.
Jyoti S. Mayadev, MD, says that pembrolizumab in combination with chemoradiation will be seamlessly incorporated into her institution’s treatment of those with FIGO 2014 stage III to IVA cervical cancer following the regimen’s FDA approval.
Domenica Lorusso, MD, PhD, says that paying attention to the quality of chemoradiotherapy is imperative to feeling confident about the potential addition of pembrolizumab for locally advanced cervical cancer.
Guidelines from the Society of Gynecologic Oncology may help with managing the ongoing chemotherapy shortage in the treatment of patients with gynecologic cancers, according to Brian Slomovitz, MD, MS, FACOG.
Interim data reveal favorable responses in patients with low-grade serous ovarian cancer treated with avutometinib plus defactinib, according to Susana N. Banerjee, MD.
Brian Slomovitz, MD, MS, FACOG, notes that sometimes there is a need to substitute cisplatin for carboplatin, and vice versa, to best manage gynecologic cancers during the chemotherapy shortage.
Findings from the phase 3 MIRASOL trial support mirvetuximab soravtansine as a standard treatment option for platinum-resistant ovarian cancer, according to Ritu Salani, MD.
Trastuzumab deruxtecan appears to elicit ‘impressive’ responses among patients with HER2-positive gynecologic cancers regardless of immunohistochemistry in the phase 2 DESTINY-PanTumor02 trial.
Related Content