Recently published research, led by Danny Dhanasekaran, PhD, Associate Director for Basic Research at the Stephenson Cancer Center, may help identify new strategies for the development of targeted ovarian cancer drugs. This research was published in Cancer Research, one of the nation’s most highly regarded cancer scientific journals.
According to the American Cancer Society, more than 22,240 women will receive an ovarian cancer diagnosis in 2018 and 14,070 will die from the disease. Ovarian cancer causes more deaths than any other gynecologic cancer.
Targeted cancer therapies are drugs that block tumor cells by interfering with the specific molecular interactions that are involved in the growth, progression and spread of cancer. Targeted therapies act on specific molecular targets, whereas traditional chemotherapy acts on both normal and tumor cells. For this reason, targeted therapies often have fewer and less serious side effects.
Dhanasekaran’s research seeks to better understand the molecular processes that “reprogram” cells as they shift from normal to cancerous. This reprogramming involves a complex interplay of molecules and signaling pathways, both inside the cell and in the cell’s surrounding micro-environment.
Dhanasekaran’s research focuses specifically on the role of lysophosphatidic acid (LPA), which is present in large quantities in ovarian cancer cells and may be involved in molecular signaling pathways that lead normal ovarian cells to turn cancerous. Using ovarian cancer tissue samples, Dhanasekaran’s team demonstrated that a specific molecular inhibitor, 3-bromopyruvate, can disrupt these signaling pathways and reduce the proliferation of ovarian cancer cells.
“These findings suggest a critical role for LPA in metabolic reprogramming of ovarian cancer cells,” said Dhanasekaran. “They hopefully bring us one step closer to the development of targeted drugs for ovarian cancer.”
The therapeutic efficacy of disrupting this pathway as a targeted strategy for ovarian cancer treatment is being currently evaluated in preclinical models.
“This year alone, ovarian cancer will claim the lives of over 14,000 women, underscoring the desperate need for novel, highly-effective therapy specific to this disease,” said Dr. Katherine Moxley. “This research has not only improved our understanding of ovarian cancer metabolism, but is a tremendous first step towards identifying novel ‘ovarian cancer-specific’ treatments. We are hopeful that the preclinical success of this therapeutic strategy will translate into novel drug development to improve survival for women battling this terrible disease.”
The article, “LPA Induces Metabolic Reprogramming in Ovarian Cancer via a Pseudohypoxic Response,” was published in Volume 78, Issue 8 of Cancer Research. This journal is published by the American Association of Cancer Research, which focuses on original high-impact cancer research.
This global oncology research includes collaborative efforts from investigators representing different cancer centers across the nation. Stephenson Cancer Center researchers involved in the study include: Ji Hee Ha; Rangasudhagar Radhakrishnan; Muralidharan Jayaraman; Mingda Yan; Jeremy D. Ward; Kar-Ming Fung; Katherine Moxley; Priyabrata Mukherjee; and Danny N. Dhanasekaran. Additional researchers involved include: Anil K. Sood (The University of Texas MD Anderson Cancer Center); Ciro Isidoro (Università del Piemonte Orientale, Novara, Italy); and Yong Sang Song (Cancer Research Institute, Seoul National University, College of Medicine, Seoul, Korea).
Dhanasekaran is the Samuel Roberts Noble Foundation Endowed Chair in Cancer Research.
Scientific instrumentation and other infrastructure to support this research was funded in part by the Oklahoma Tobacco Settlement Endowment Trust (TSET). An endowment created by the voters in 2000 to improve the health of Oklahomans, TSET is dedicated to reducing the state’s leading causes of preventable death – cancer and cardiovascular disease – caused by tobacco use and obesity.