city doctor gets $430,000 to fight cancer

No pain, big gain.

A Hamilton cancer researcher has been awarded a $430,000 grant from the Canadian Breast Cancer Foundation to better understand the cellular mechanisms that can lead to the intense pain suffered by patients with certain types of cancer.

But early results from the work of Dr. Gurmit Singh and his team at the Juravinski Cancer Centre suggest a promising new way to block the pain could also be a novel way to fight cancer that has spread to bones.

Advances in treating breast cancer have resulted in better drugs, which have proven to be a double-edged sword.

“People are living longer but they’re complaining that they are in a lot of pain,” said Singh, who is also a professor in McMaster University’s Department of Pathology and Molecular Medicine.

Pain has often been shoved to the side in medicine’s quest for cures and better treatments, he added.

“Pain is a symptom, not a disease, and most organizations don’t fund pain research,” said Singh. “They fund what they think will be a cure for the disease.

“This may not cure the cancer but it will definitely deal with a symptom of the disease — pain — which is extremely important for quality of life.”

Cancers become particularly deadly when tumour cells break off and spread, or metastasize, to a secondary site. In the case of breast cancer, secondary tumours are most likely to develop in a patient’s bones.

Up to 85 per cent of breast cancer patients will develop bone metastases, and about half of those will suffer a fracture. Yet up to 70 per cent of prostate cancer patients will develop bone metastases, and only 6 per cent of those will suffer a fracture.

Singh became curious about the mechanisms that cause both the increase in fractures and pain in breast cancer patients.

When tumour cells break down bone, growth factors are released, which act like fertilizer and cause the tumour cells to grow faster and multiply. It’s a vicious cycle — as more bone gets chewed up, more growth factor is released and the tumour cells thrive.

As the tumour cells thrive, they also release an amino acid called glutamate.

Tumour cells are a bit like an out-of-control furnace — they’re constantly burning energy, but that comes at a cost. Lots of garbage, called reactive oxygen species, builds up inside the tumour cell, and that garbage needs to get dumped outside for the cell to keep functioning.

On the surface of the tumour cell are pumps that bring in another amino acid called cystine that helps break down the garbage. As cystine is pumped in, glutamate is pumped out of the tumour cell.

To the tumour cell, glutamate is just garbage kicked to the curb. But it turns out that glutamate is also a neurotransmitter that causes the bone to start breaking down faster than it can be built up.

It also turns out that glutamate is a very powerful stimulator of pain receptors, and the inside of bone is filled with nerve endings. As the tumour grows, more glutamate is released and more pain receptors are stimulated, sending the pain signal to the spinal cord then up to the brain.

“The spinal cord is also very plastic,” said Singh. “If this signal continues on, it gets etched in and once it’s etched in, you’ve got chronic pain.

“If you wait too long, this circuit gets soldered in.”

The goal of Singh’s research is to find a way to block pain right at the source, rather than having to treat patients with powerful opiate drugs that act on the brain and lead to a poor quality of life.

Using animal models, Singh and his team are going to test a prototype compound that blocks the pump that brings cystine in and dumps glutamate out.

With the pump deactivated, Singh said, it’s also possible the tumour cells might die from the buildup of garbage inside.

“If we can block that, these cells may implode,” said Singh. “So it may actually be an anti-cancer agent and also something that can stop pain.”

The next phase of research for Singh’s group is to find ways to shut off the enzyme that creates the garbage inside a tumour cell in the first place.

They figured out a way to mass produce the enzyme in bacteria, then used a special machine to test 35,000 different compounds.

Out of the 35,000, two compounds were found that inhibit the enzyme and are safe to take.

The Hamilton Spectator
Fri May 14 2010
Page: A6
Section: Local
Byline: Steve Buist
Source: The Hamilton Spectator