Ovarian cancer (OvCa) is a devastating disease that results in around 15,000 deaths among women in the U.S. each year. Despite substantial efforts to improve cancer treatment, conventional therapy is largely ineffective and the patient survival remains poor. Researchers cannot explain all changes in physical health of women with OvCa based on biological factors alone. Clinical observations strongly indicate that psychological stress related to diagnosis, treatment and social isolation can fuel cancer growth and studies on animals strongly support that idea. Therefore, we aim, through computational analysis of available datasets, to find genes triggered by stress and enzymatic biomarkers that identify the OvCa patients particularly sensitive to stress. Next, we want to switch those genes off in the tumor through nanoparticles to overcome stress effects and improve patients’ survival. Upon computational analyses and biological validation, we identified HSD11B1 that is the rate-limiting enzyme important for cortisol generation. Promoter analyses found that HSD11B1 is regulated by pro-inflammatory cytokines (e.g. IL1A and IL6) that are abundantly produced in OvCa patients with depression. Our mechanistic in vivo studies demonstrated that intra-tumoral HSD11B1 augmented cortisol levels in the blood in the restraint stress OvCa orthotropic mouse model. Overall, these findings provide novel insights into stress actions in OvCa and, also, facilitate the discovery of clinically important targets for therapeutic interventions.
Dr. Chatterjee is post-doctoral fellow under the mentorship of Dr. Anil Sood at the MD Anderson Cancer Center whose lab specializes in understanding the mechanisms of ovarian cancer growth and metastasis. Dr. Chatterjee did her Master’s work in pharmacology from west Bengal University of Technology in India. She subsequently carried out her Ph.D. work from Jadavpur University. She has received several awards during her doctoral research work including a research fellowship, and young scientist awards. She was involved in identifying novel therapeutic approaches for inflammation aimed at targeting cancer progression. In Dr. Sood’s lab, her research will focus on understanding the mechanisms involved in shaping the ovarian cancer microenvironment and in developing new strategies for therapeutic targeting using non-coding RNAs.