Preliminary findings on two studies on ovarian cancer headed by Dr. Gil Mor
were presented at the April 15 meeting of the American Association for Cancer
Research (AACR) Meeting in San Diego, California. — By Karen Peart
T H I S
Mor is associate professor in the Department of Obstetrics, Gynecology and
Reproductive Sciences at Yale School of Medicine. The presentations focused
on a possible source of ovarian cancer’s resistance to chemotherapy and
on a drug compound that might be used to overcome that resistance.
Role of stem cells in ovarian cancer
Mor reported that researchers at Yale School of Medicine have identified, characterized
and cloned ovarian cancer stem cells and have shown that these stem cells may
be the source of ovarian cancer’s recurrence and its resistance to chemotherapy.
“These results bring us closer to more effective and targeted treatment
for epithelial ovarian cancer, one of the most lethal forms of cancer,” Mor
said.
Cancerous tumors are made up of cells that are both cancerous and non-cancerous.
Within cancerous cells, there is a further subclass referred to as cancer stem
cells, which can replicate indefinitely.
“Present chemotherapy modalities eliminate the bulk of the tumor cells,
but cannot eliminate a core of these cancer stem cells that have a high capacity
for renewal,” said Mor, who is also a member of the Yale Cancer Center. “Identification
of these cells, as we have done here, is the first step in the development of
therapeutic modalities.”
Mor and colleagues isolated cells from 80 human samples of either peritoneal
fluid or solid tumors. The cancer stem cells that were identified were positive
for traditional cancer stem cell markers including CD44 and MyD88. These cells
also showed a high capacity for repair and self-renewal.
The isolated cells formed tumors 100% of the time. Within those tumors, 10%
of the cells were positive for cancer stem cell marker CD44, while 90% were
CD44 negative.
Mor and his team were able to isolate and clone the ovarian cancer stem cells.
They found that these cells were highly resistant to conventional chemotherapy
while the non-cancer stem cells responded to treatment. “Isolating and
cloning these cells will lead to development of new treatments to target and
eliminate the cancer stem cells and hopefully prevent recurrence,” said
Mor.
Drug compound for treatment of disease
In a discovery that may be useful for maintaining remission in chemo-resistant
ovarian cancer, pre-clinical studies have shown the drug compound NV-128 can
induce the death of ovarian cancer cells by halting the activation of a protein
pathway called mTOR, reported Mor and associate research scientist Dr. Ayesha
Alvero.
In cancer cells, mTOR signals enhance tumor growth and may be associated with
resistance to conventional therapies. Inhibition of mTOR could shut down many
of these survival pathways, including proteins that protect the mitochondria
of cancer cells.
NV-128, developed by Novogen Limited, holds promise as a more targeted therapy
for ovarian cancer because it works differently from traditional therapies
that are dependent on enzymes known as caspases to trigger cell death. Therapies
using caspases to kill cancer cells can be ineffective in chemo-resistant cancer
cells due to mutations that short-circuit signals that trigger cancer cell
death.
“We consider that the capacity of NV-128 to trigger caspase-independent
cell death, in otherwise chemo-resistant ovarian cancer cells, opens new possibilities
for the use of NV-128 as a potential addition to conventional chemotherapy targeting
ovarian cancer cells,” said Mor.
In the context of developing therapies for late-stage ovarian cancer, Mor said,
the finding may be “a key step to the development of alternative targeted
therapy for patients with cancer recurrence.”
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IN MEMORIAM
Dr. Steven Hebert: Discoveries illuminated kidney processes
G.K. Hunter: Was a scholar of Renaissance literature
Let the sun shine
Campus Notes
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