Study Published in International Journal of Cancer
Genkyotex (Euronext Paris & Brussels: FR00011790542 – GKTX), a biopharmaceutical company and the leader in NOX therapies, announced today that data in a preclinical model showed that GKT831, the Company’s NOX1 and NOX4 inhibitor, efficiently targeted cancer associated fibroblasts (CAFs) in prostate cancer and abrogated the pro-tumorigenic influence of the tumor micro-environment. The results of this study, which was conducted by Dr. Natalie Sampson and colleagues at the Medical University of Innsbruck, were published in the International Journal of Cancer (https://doi.org/10.1002/ijc.31316).
CAFs are an essential component of the tumor-associated stromal microenvironment, which is a major driver of prostate cancer progression and independent predictor of disease prognosis.
CAFs are largely driven by cancer-derived cytokines, such as transforming growth factor-β (TGFβ1), which fuels cancer cell proliferation and migration. The results of this study showed that stromal areas with clusters of intense NOX4 staining were localized adjacent to tumor foci with abundant TGFβ1 expression. In vitro, GKT831 significantly reduced TGFβ1-induced expression of CAF markers at both the mRNA and protein levels.
Additionally, GKT831 halted the proliferation and migration of prostate cancer cells. Collectively, these data demonstrated that GKT831 efficiently disrupts the TGFβ1-NOX4 signaling axis underlying reciprocal epithelial-stromal cell crosstalk, fibroblast activation and stromal-driven tumor cell promoting properties.
“These studies highlight the central role of NOX4 in driving CAF activation in prostate cancer. Importantly, the results demonstrate that GKT831 abrogates the tumor promoting properties of CAFs, further supporting our focus on the therapeutic potential of NOX inhibitors in oncology. These new data follow previous preclinical results published mid-2017, showing that GKT831 can efficiently target CAFs and delay tumor growth in head and neck cancer,” said Philippe Wiesel, M.D., Executive Vice President and Chief Medical Officer of Genkyotex.
The role of NOX4 in CAFs activation shares many similarities with its role in the activation of myofibroblasts, a key characteristic of fibrogenesis in many fibrotic diseases. GKT831 has also demonstrated potent anti-fibrotic activity in multiple preclinical models of liver, lung, skin, and renal fibrosis. Genkyotex is currently assessing the safety and efficacy of GKT831 in patients with respectively primary biliary cholangitis and diabetic kidney disease, two progressive fibrotic disorders, in two ongoing different Phase 2 trials.