Chemotherapy-Induced Changes to the Tumor Microenvironment and Outcomes in Ovarian Cancer
Posted: Tuesday, December 22, 2020
According to findings published in Clinical Cancer Research, understanding chemotherapy-induced changes to the tumor microenvironment may result in improved outcomes in ovarian cancer. Most patients with ovarian cancer experience treatment response, but most also experience disease recurrence. In addition, Benjamin G. Bitler, PhD, of the University of Colorado Cancer Center, and colleagues also identified a novel interleukin-6 (IL-6)/IER3 (immediate early response 3) signaling axis, which might be responsible for chemoresistance and disease recurrence.
“There is a small percentage of patients [who] will never recur or [will] remain in remission beyond 5 years,” noted Dr. Bitler in a university press release. “We are working to be able to better predict a [patient’s] response to chemotherapy.”
Because survival outcomes are improved by the achievement of optimal surgical cytoreduction, which in turn is improved by neoadjuvant chemotherapy, the study analyzed pre- and post-neoadjuvant chemotherapy tumor tissues from six patients with high-grade serous ovarian cancer. The mRNA levels of 770 genes, including 14 housekeeping genes, and the cytokine levels of 39 prechemotherapy ascites samples were measured. Reverse-phase protein array was conducted on a group of matched tumors. A total of 128 annotated ovarian tumors were included in a tissue microarray.
The data resulting from reverse-phase protein array were consistent with those of mRNA, indicating elevated immune infiltration. Among postchemotherapy genes, IL-6 was the most upregulated, whereas elevated IL-6 in prechemotherapy samples was associated with faster disease recurrence. When NanoString Technologies (n = 12), reverse-phase protein array (n = 4), and cytokine (n = 39) data were included, an activated inflammatory signaling network was detected. In postchemotherapy samples, a correlation was noted between induced IL-6 and IER3 and an inferior response to chemotherapy treatment as well as a faster time to disease recurrence.
Disclosure: For full disclosures of the study authors, visit clincancerres.aacrjournals.org.
