Cancer cells hide by going dormant

Cancer cells hide by going dormant, Princess Margaret study finds


Published on Thursday December 13, 2012



Becky Shink/The Associated Press

Toronto-based researchers have discovered that cancer recurs in a way that hadn't previously been thought.

In a major breakthrough that will
change the way cancer is studied and treated in the future, Toronto
scientists have discovered a key reason why many tumours may return
after chemotherapy.

In a new study, researchers at the Princess Margaret Cancer Centre
have shown that some of the cells that drive tumour growth hide from
common chemotherapy drugs by going “dormant” — reigniting the disease
when they awaken after treatments end.

“That’s where this paper lies is to
begin to add more depth (and) complexity to why cancers come back, why
they recur,” says renowned stem cell scientist John Dick, whose paper
was released Thursday by the journal Science.

“This will stimulate a lot of activity,” says Dick, the study’s senior author.

Luba Slatkovska, head of research
with Canadian Cancer Society’s Ontario division agrees, saying the
discovery represents a paradigm shift for research into the disease.

“John Dick is one of those
researchers who is really changing the way we think about cancer, and
this is another example,” Slatkovska says.

“We think that it’s going to become one of the new hot topics … in cancer research,” she says.

Dick,
also a molecular geneticist at the University of Toronto, says the
newly-discovered dormant cells have precisely the same genetic mutations
as those active ones that drove the original tumour to begin with.

Cancers occur when genetic mutations to a cell’s DNA cause them to replicate in an out-of-control fashion.

And it was assumed, Dick says, that
cancers returned after chemotherapy because of subsequent genetic
mutations that made them resistant to the drugs being used against the
original tumours.

“And that is certainly true in many cases,” he says.

But the discovery of the
genetically-identical dormant cells shows that other forces are at play
in cancer recurrence and that these nongenetic forces must now command
the attention of the oncology community.

“We thought that there would have
been a different set of (genetic) mutations, a different spectrum of
mutations that would have explained why (the recurring) cells were
resistant to chemotherapy,” Dick says.

“And in a sense that’s not what we
saw. We saw . . . that they seemed to be quite similar or essentially
identical (genetically) and so something else was driving their
resistance to therapy.”

Dick, who last made headlines
in 2011 when he led the team that first isolated blood stem cells, says
that “something else” could include the micro-environments in which the
dormant cells are located within the tumour.

“Is it that cells are sitting in the tumour in a location that makes them dormant?” he asks.

Dick says that along with cancer
cells, tumours contain a number of normal tissues, including blood
vessels and immune system agents.

“And it appears that tumour cells can
lie in proximity to these non-tumour cells and that can influence their
behaviour,” Dick says.

“So that is one of the properties we
should be looking for, we should be looking for where tumour cells are
sitting, who they’re close to and what kind of signals they are
receiving.”

Dick, whose team grew human
colorectal cancers in mice for the research, says only one in every
several thousand cells in a tumour can actually drive its growth.

And many of these tumour drivers are
susceptible to chemotherapies because most of the drugs now used in
cancer treatment target cells that multiply at abnormal speeds — a
signature of the disease in all its forms.

But if some of these stem-cell-like
cancer drivers are dormant — in effect hiding their ability to rapidly
replicate — the drugs will pass them over.

“Some of (the cancer driver cells)
are actually quite sensitive (to chemotherapy) and other ones,
particularly those ones that come from these so-called dormant cells are
much more resistant,” Dick says.

“And that can be responsible for relapse.”

Dick says scientists now need to look for ways to kill these skulking cells or to control the factors that can awaken them.

“We need to understand the biological properties — not necessarily the genetic properties — that are driving dormancy,” he says.

An understanding of these nongenetic properties could lead to an entirely new generation of cancer medications, Dick says.

Slatkovska, whose society has funded
Dick in the past but was not involved in the current study, says she can
imagine the creation of drugs that could wake up the sleeping cells and
expose them to killer chemo.

Drugs that could interfere with the
external signals that call the dormant cells out of sleep could also
become a weapon in the oncology arsenal, Dick says.

“What our paper is saying is that on
top of (targeting) the genetic properties of these cells you have to
target the biological properties to be more effective,” Dick says.
“Everything doesn’t just rest on genetics.”


Source:-
http://www.thestar.com/news/gta/article/1301826--cancer-cells-hide-by-going-dormant-princess-margaret-study-finds