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Meet The Molecule That Can Supercharge Cancer-Killing Viruses

Since the turn of the millennium, the fight against cancer has seen significant progress in all areas of treatment. One of the most promising routes happens to be through a process known as oncolytic virotherapy, or simply OV. The term may be a mouthful but the process at its core is incredibly simple and effective.
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Killer T cells (green and red) surround a cancer cell (blue, center). Killer T cells are immune cells that target and remove unhealthy cells, including cancer cells and virus-infected cells. Credit: NICHD/J. Lippincott-Schwartz
NICHD NIH Flickr
Killer T cells (green and red) surround a cancer cell (blue, center). Killer T cells are immune cells that target and remove unhealthy cells, including cancer cells and virus-infected cells. Credit: NICHD/J. Lippincott-Schwartz

Since the turn of the millennium, the fight against cancer has seen significant progress in all areas of treatment. One of the most promising routes happens to be through a process known as oncolytic virotherapy, or simply OV. The term may be a mouthful but the process at its core is incredibly simple and effective.

Viruses need to live in cells to survive. But not every cell type will work, as most virus types prefer a particular cellular home. The common cold likes cells in the respiratory tract. Rabies prefers nerve cells. Norovirus only lives in the intestinal cells. When one of these viruses finds the right cell type, entry occurs using a lock-and-key approach (better known as receptor-ligand interaction). Once inside, the virus can go about its business.

Typically when a virus infects a cell, it's for the most part doomed. The process can take as little as a few hours depending on how fast the virus can multiply. The cell may put up a fight, but most of the time the end result is the same. In the process, the viruses held inside are released and are allowed to spread to other cells.

If the virus prefers a cancer cell, then infection can potentially destroy the tumour, leading to remission.

When this viral invasion occurs, it's usually an unwanted process as we end up getting sick. But in some cases, an infection can be good for us. If the virus prefers a cancer cell, then infection can potentially destroy the tumour, leading to remission. The concept has been around for over 60 years and has been sought for human cancer treatment for close to four decades.

Last year, OV took a huge step forward when the Federal Drug Administration in the United States officially approved a virus-based treatment for melanoma. The news sent waves of hope that the use of viruses may one day put an end to cancer.

Unfortunately, there is a catch to OV. It's still an invasion of the cell meaning the cancer cell will not take too kindly to the intrusion. While the cell may be doomed, depending on the strength of the defence, the virus may not get the job done. This has been one of the most troublesome hurdles for OV researchers and stands as a significant block in the progress of these treatments.

Now there may be a way forward. Last week, a team of group of Canadian researchers unveiled a new way to deal with cancer cell defences. Based on the results, the addition of a small molecule known as a sensitizer may be the key to ensuring OV success.

As the name implies, a sensitizer is a molecule with the ability to neutralize the fight within a cancer cell. Back in 2010, a method was developed to identify these chemicals. Not surprisingly, several potential candidates were found. But the process didn't stop there. In addition to natural molecules, synthetic analogues were developed and tested. The team tested dozens of different molecules in the hopes of finding one or several possible sensitizers. In total, they found 14. With these in hand, they then proceeded with a number of tests to prove these molecules were effective.

The tests followed a path similar to new antibiotics or other pharmaceutical agents. They first attempted to demonstrate the benefit of the molecule in OV using cell cultures. The process was relatively simple and did not incur any significant ethical issues.

If any of the molecules passed the test, the next stage was to use actual tumours collected from animals. This particular stage was considered to be the most important as it provided the right type of environment to determine if there was reason to move to living creatures.

From the 14, only four made the cut. They were then used in mice to determine whether they could be tolerated by the animals. This was an even harder test and as expected, three of the candidates did not impress. That left only one -- Number 28 -- to be taken to the ultimate step.

The test was simple. Take a mouse suffering from cancer and attempt OV along with candidate #28. But the importance of this experiment could not be understated. After all the years of testing and trials, this was the make or break moment.

It worked.

When the results came back, #28 had proven itself. The cancer progression had slowed and, more importantly, the mice lived longer than expected. When compared to OV treatment alone, the addition of #28 significantly improved the treatment. The milestone revealed just how the addition of a small molecule may one day make OV a true cancer cure.

Despite the good news, don't expect the sensitizers to be used for some time. There are still many hurdles ahead and the possibility of a failure is always present. But considering the importance of cancer in our everyday lives, this moment of success can foster even more hope that a cure may come thanks to our microbial terrestrial co-inhabitants.

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