CANCER
July 11, 2014

A Deadly Genetic Partnership

Researchers have uncovered a genetic combo that drives cancer's spread. Luckily, there also seems to be a chink in its armor.

Since the completion of the Human Genome Project, scientists have sought to identify which genes are responsible for causing specific diseases, with a particular emphasis on those that cause cancer. One gene, known as “MYC”, has long been linked to cancer and is estimated to cause about 20% of all cases.

Fortunately, new findings from the Masonic Cancer Center at the University of Minnesota suggest that MYC might have a weak spot in its armor that can be exploited to stop tumor growth.

The study suggests MYC does not act alone. Rather, it forms a gene partnership with another gene, PVT1, and this partnership could be the key to understanding how MYC fuels cancer by amplifying growth of cancerous cells.

Not only do these genes amplify together, PVT1 helps boost the MYC protein's ability to carry out its dangerous activities in the cell… [N]ow we've identified it, we can look for ways to uncouple this dangerous partnership.

“We knew MYC amplifications cause cancer. But we also know that MYC does not amplify alone. It often pairs with adjacent chromosomal regions. We wanted to know if the neighboring genes played a role,” lead author Anindya Bagchi said in a statement.

“We took a chance and were surprised to find this unexpected and counter-intuitive partnership between MYC and its neighbor, PVT1. Not only do these genes amplify together, PVT1 helps boost the MYC protein's ability to carry out its dangerous activities in the cell.”

The researchers found that mice that had both MYC and PVT1 developed cancerous growths, while mice that had either MYC or PVT1 alone did not.

“When cancer promotes a cell to make more MYC, it also increases the PVT1 in the cell, which in turn boosts the amount of MYC. It's a cycle, and now we've identified it, we can look for ways to uncouple this dangerous partnership,” said co-author David Largaespada.

In order to test this idea of a cancer-causing gene partnership, the researchers looked at several breast cancer and colorectal cancers known to be caused by MYC. For example, in colorectal cancers, a mutation causes elevated MYC levels that produce tumors. They found that eliminating the gene partner, PVT1, from these cells made the tumors nearly disappear.

More importantly, MYC has proven largely successful as a drug-target in pharmaceutical research. This new study suggests that by uncoupling MYC and PVT1, it may be possible to disable the cancer growth and maintain MYC at pre-cancerous levels. This positions PVT1 as an ideal drug target to potentially control a major cancer gene.

“This is a thrilling discovery, but there are more questions that follow,” says Bagchi. “Two major areas present themselves now for research: will breaking the nexus between MYC and PVT1 perform the same in any MYC-driven cancer, even those not driven by this specific genetic location? And how is PVT1 stabilizing or boosting MYC within the cells? This relationship will be a key to developing any drugs to target this mechanism.”

The study is published in the journal Nature.

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