A recent discovery by researchers from the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore (NUS) may lead to a new treatment strategy for an aggressive ovarian cancer subtype.
Ovarian cancer is the most deadly gynecological cancer and it is the seventh most common cancer in women worldwide. Most women with ovarian cancer are diagnosed at the advanced stage, which is more difficult to treat.
In a study led by Dr Ruby Huang, Principal Investigator at CSI Singapore, researchers identified a molecule called AXL which is found to trigger the spread of an aggressive form of ovarian cancer called the Mes subtype. This is one of two aggressive subtypes of ovarian cancer - the other subtype is called Stem-A - that was identified by Dr Huang's group in an earlier study. These two subtypes of ovarian cancers have a higher ability to undergo Epithelial-Mesenchymal Transition (EMT). EMT is the process by which epithelial cells transform into mesenchymal cells, which have been associated with aggressive metastatic cancer.
By carrying out experiments on Mes subtype ovarian cancer cells, Dr Huang and her team found that AXL, when activated, was able to interact with other proteins in the cell to form a cellular pathway that contributes to the aggressive spread of ovarian cancer cells. Results from this study were published in the journal Science Signaling.
New hope for treating advanced ovarian cancer
Currently, there is no specific treatment for the Mes ovarian cancer subtype, and the findings from this study suggest that blocking AXL could be an effective treatment option for these patients.
"Though earlier studies have suggested the role of AXL in contributing to the spreading of ovarian cancer cells, no study has investigated the AXL function in ovarian cancer with different molecular backgrounds. This study builds upon our previous efforts in understanding the biology among different ovarian cancer subtypes, and the current finding represents an advancement into novel roles of AXL in ovarian cancer and brings another layer of sophistication in ovarian cancer treatment," said Dr Huang.
The research team from CSI Singapore is collaborating with several pharmaceutical companies to develop anti-AXL drugs, in order to bring the discovery from bench to bedside for ovarian cancer treatment. Dr David Tan, who holds dual appointments with CSI Singapore and National University Cancer Institute, will be leading the clinical development of the anti-AXL treatment.
This study was carried out in collaboration with clinicians from the National University Hospital as well as scientists from Imperial College London, and supported by the National Research Foundation Singapore, Singapore Ministry of Education, and National Medical Research Council. The first author of the paper, Dr Jane Antony, had recently graduated from the joint PhD programme between NUS Graduate School for Integrative Sciences and Engineering as well as Imperial College London.
Article: The GAS6-AXL signaling network is a mesenchymal (Mes) molecular subtype-specific therapeutic target for ovarian cancer, Jane Antony, Tuan Zea Tan, Zoe Kelly, Jeffrey Low, Mahesh Choolani, Chiara Recchi, Hani Gabra, Jean Paul Thiery, and Ruby Yun-Ju Huang, Science Signaling, doi: 10.1126/scisignal.aaf8175, published 4 October 2016.