Erkut Borazanci, MD, explains discoveries surrounding the possibility of targeting the glucocorticoid receptor with experimental drug

HonorHealth Research Institute oncologist Erkut Borazanci, MD, describes how a Phase 2 clinical trial for patients with ovarian cancer has helped identify new biomarkers, or genes, that in the future could benefit patients with cancer.

The findings were presented in April at the American Association of Cancer Research (AACR) annual meeting in Orlando, Fla., and Dr. Borazanci was one of the authors of the presentation.

Patients were given either nab-paclitaxel, an FDA-approved drug that has been effective against a variety of cancers in other studies, or they received a combination of that drug plus an experimental drug made by Menlo Park-based Corcept Therapeutics Incorporated.

That experimental drug, called relacorilant, targets the glucocorticoid receptor, which regulates many bodily functions and has been implicated in drug resistance. The hope is this drug  can help diminish drug resistance, so that chemotherapies can be more effective.

Experimental drug appears to activate CLEC10A

In the Phase 2 study of 178 patients with ovarian cancer, patients treated with the combination therapy saw activation of a gene called CLEC10A, which Dr. Borazanci explained appears to encode a protein involved with how our body fights off foreign invaders, whether they be viruses or cancer cells.

CLEC10A was one of eight genes apparently most strongly affected by this drug combination, which appeared to suppress four genes: CDKN1C, TNFRSF17, BRIP1 and PDK1; while activating four other genes: LILRB4, FPR3, CCR2 and CLEC10A. Activation of CLEC10A correlated with improved overall survival.

In addition to the Phase 2 study in ovarian cancer, relacorilant has been studied in pancreatic cancer, prostate cancer and other solid tumors. Dr. Borazanci led a study that involved 43 patients with refractory pancreatic cancer; refractory meaning it does not respond or is resistant to treatment. These patients had already undergone at least two previous lines of treatments. Following treatment with the combination therapy, a similar pattern for changes in gene expression was seen in this study as in the Phase 2 ovarian cancer study, including CLEC10A activation, lending further support to these findings.

In yet a third study involving Dr. Borazanci’s cancer patients at HonorHealth Research Institute — this one a Phase 1 solid tumor study whose results were published last year in Clinical Cancer Research, a publication of AACR — researchers investigated whether combining relacorilant with taxanes, such as nab-paclitaxel, could enhance antitumor activity. Once again, a similar pattern of gene expression was observed in that study. Other studies with glucocorticoid receptor-targeting drugs and different combination partners yielded consistent results, suggesting that these genes are reliable indicators of glucocorticoid receptor activity across multiple tumor types.

Gaining a better understanding of glucocorticoid receptors

“There’s still a lot to be understood about how the glucocorticoid receptor works,” Dr. Borazanci said. “We’re starting to define that process better, and the exciting thing is that there is seemingly a marker, CLEC10A, related to targeting the glucocorticoid receptor that could potentially be impactful in treating patients with advanced cancer.

“After seeing this data, the idea of exploring relacorilant in other combinations — especially with immune therapy combinations — is a promising next step,” he said.

Ovarian cancer is the fifth leading cause of cancer-related death in women in the U.S., with nearly 20,000 women annually diagnosed with the disease, and more than 13,000 deaths.