07:19am Tuesday 31 March 2020

Preclinical study identifies 'master' proto-oncogene that regulates stress-induced ovarian cancer metastasis

Building on the Stress-Cancer Connection
For the past 13 years, Sood’s research efforts have focused on the effects of chronic stress on cancer metastasis. The latest study helps form a more comprehensive picture on the impact of and biological mechanics of chronic stress on ovarian cancer, as well as the role of beta blockers in slowing disease progression. Previous studies have shown:

  • Chronic stress triggers a chain of molecular events that protects breakaway ovarian cells from destruction, as heightened levels of the fight-or-flight hormones epinephrine and norepinephrine permit more malignant cells to safely leave the primary tumor – a necessary step in metastasis and cancer progression.
  • When mice with ovarian cancer are stressed, their tumors grow and spread more quickly, but the effect can be blocked using propranolol, a beta blocker commonly prescribed for heart disease.

Future research will focus on other biological mechanisms that may be affected by stress. Eventually, Sood hopes his studies will help identify the cancer patients most likely to benefit from beta blockers and other stress interventions. He is also looking at the impact of stress on other diseases, such as gastrointestinal disorders.

“This is a major step forward in understanding the biology and impact of stress on cancer progression and it opens the door to study drugs that could inhibit this unique signaling pathway,” Sood said.

The current study was supported by grants from the NCI (F31CA126474), NIH (numbers CA101642, CA140933, CA104825, CA110793, CA109298, P50CA083639, P50CA098258, CA128797, RC2GM092599, U54CA96300, and U54CA96297), the Ovarian Cancer Research Fund, Zarrow Foundation, Department of Defense (numbers OC073399, W81XWH-10-1-0158, OC100237, and BC085265) Betty Ann Asche Murray Distinguished Professorship, the Marcus Foundation, RGK Foundation, Gilder Foundation, the estate of C.G. Johnson Jr., the Laura and John Arnold Foundation and the Blanton-Davis Ovarian Cancer Research Programme.

Co-authors of the paper from MD Anderson included Guillermo N. Armaiz-Pena Ph.D.; Julie K. Allen; Rebecca L. Stone, M.D.; Alpa M. Nick, M.D.; Yvonne G. Lin, M.D.; Liz Y. Han, M.D.; Lingegowda S. Mangala; Gabriel J. Villares; Pablo Vivas-Mejia, Ph.D.; Christian Rodriguez, Ph.D.; Archana S. Nagaraja; Kshipa M. Gharpure; Mian M.K. Shazhad, M.D.; Maya Zigler; Michael T. Deavers, M.D.; Gary E. Gallick, Ph.D; Menashe Bar-Eli, Ph.D.; and Gabriel Lopez-Berestein, M.D. Sood, Allen, Villares, Nagaraja, Gharpure and Zigler are also affiliated with The University of Texas Health Science Center. Other co-authors included Madeline Torres-Lugo, Ph.D., Gustavo E. Lopez, Ph.D. and Anthony Cruz, University of Puerto Rico; Zheng Wu, Ph.D., Robert D. English, Ph.D., Kizhake V. Soman, Ph.D. and John E. Wiktorowicz, Ph.D., University of Texas Medical Branch; Alexander Zien, Ph.D., Theodoros G. Soldatos and David B. Jackson, Molecular Health GmbH; Tom Young, Ph.D., Lehman College; Koen De Geest, M.D. and Susan K. Lutgendorf, Ph.D., University of Iowa; Steve W. Cole, Ph.D., University of California, Los Angeles.

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