By Chardelle Prevatt & Anushka Jayasuriya – May 31, 2017
In 2016, over 2,800 Canadian women were diagnosed with ovarian cancer, with 1,750 succumbing to the disease. Located in the pelvis, the ovaries are a pair of organs in the female reproductive system that produces eggs and hormones. Epithelial ovarian cancer (EOC) results from malignant cancer cells forming in the tissues covering the ovaries.
When detected early, ovarian cancer is treatable with surgery and chemotherapy. However, relapse is almost inevitable once the disease has progressed. It is estimated that 75% of EOC patients relapse within 18 months of treatment, developing chemotherapy-resistance. Consequently, there is a dire need for novel therapeutic targets and reliable models to fight against chemotherapy-resistant EOC cells.
A research team, including GlycoNet scientists Drs. Frank Schweizer and Gilbert Arthur in collaboration with Dr. Mark Nachtigal, has revealed potential solutions to treat EOC in a paper published in the Journal of Experimental and Clinical Cancer Research. The researchers have screened a novel class of compounds against chemotherapy-resistant cells using a 3D, non-adherent culture model which is a more relevant clinical model.
“Current chemotherapy against ovarian cancer involves damaging DNA, preventing DNA synthesis, or stopping cell proliferation,” said Dr. Schweizer. “The most common chemotherapy treatments are platinum-based drugs which activate the cells’ apoptotic pathway, leading to cell death.”
“With recurring EOC, cells have found ways to evade apoptosis by being inherently resistant or developing resistance to platinum-based therapeutics,” added Dr. Arthur. “Glycosylated antitumor ether lipids (GAELs) are promising new agents for targeting these chemo-resistant cells.”
Past studies suggest that GAELs are cytotoxic to a range of cancer cells and cancer stem cells by affecting apoptosis-independent pathways. Therefore, GAELs can potentially help cancer cells to overcome resistance. However, little research has examined the effects of GAELs on EOC cells.
Preliminary results from the team’s experiments indicate that GAELs effectively killed both platinum-sensitive and platinum-resistant EOC cell lines as well as EOC cells isolated from ovarian cancer patients resistant to chemotherapy. Remarkably, only a fraction of the doses of GAELs was required to destroy the EOC cells, compared to a conventional, platinum-based drug called Cisplatin.
“Our results show these GAELs as promising primary therapeutics, with the potential for higher tolerance in patients,” said Dr. Schweizer. “We’re looking forward to conducting further studies on the tolerability and efficacy of these GAELs in animal models.”
To view the full paper.