July 31, 2013
Super Mouse Gene Paves Path For New Cancer Treatment
Alan McStravick for redOrbit.com - Your Universe Online
The mouse as a model for genetic study has been a relationship our furry friends have served well in. The mouse is a convenient subject of study for its close mammalian similarities to we humans as well as for their short reproductive and growth cycles. Back in 2007, researchers at the University of Kentucky genetically manipulated one of these creatures to become a so-called "super mouse." And from this genetic strain of mouse have come several new lines of research and study aimed at the prevention and treatment of various types of cancer.
A team of University of Kentucky researchers led by Vivek Rangnekar, professor of microbiology, immunology and molecular genetics, discovered a gene known as Par 4 which targets and kills cancer cells while leaving healthy cells alone. It was the discovery of Par 4 that let Rangnekar's team develop the cancer resistant super mice.
The super mouse has been subsequently utilized by researchers across the nation for their own cancer studies. Most recently, a team from the University of Pennsylvania published their findings on how Par 4 downregulation affects breast cancer recurrence.
Rangnekar, along with colleagues Tripti Shrestha-Bhattarai and Nikhil Hebbar, published an article for the journal Cancer Cell which looked at the Penn study and noted that its findings could be instrumental in the future development of novel treatments for breast cancer.
Statistics on the disease - particularly its rates of recurrence - are why the Penn study is so exciting. As it stands, breast cancer is currently the second leading cause of cancer death in women. Once an initial diagnosis is treated, a full 20 percent of women will experience a cancer relapse within 10 years time. Furthermore, patients diagnosed with so-called triple-negative breast cancer, which does not express the genes for a number of protein-hormone receptors, experience even higher rates of recurrence. As oncologists note, these more aggressive cancers are more difficult to treat due to their resistance to standard-of-care therapies.
In the Penn study, the team was able to definitively show how women who experienced breast cancer relapse were also experiencing a suppression of the Par 4 gene. It was the lack of this gene's protein product that ultimately allowed the cancerous cells to survive and thrive despite the patients having undergone a full course of treatment. By identifying how a suppressed Par 4 protein level relates to relapse, the team believes their findings may soon make it easier to determine which patients are at highest risk for cancer recurrence.
"What this tells us is that low Par-4 may act as a predictor of breast cancer recurrence," said Rangnekar, associate director for U of K Markey Cancer Center. "This is important, because although this group studied only breast cancer, their observations may be relevant to recurrence in a broad range of cancer types because Par-4 is a general tumor suppressor gene."
As Rangnekar points out, there are other known 'tumor suppressor' genes. However, what makes Par 4 so unique is its inability to mutate as frequently as the other known suppressors.
Additionally, Par 4 is selective in the cells it targets, killing only cancer cells and leaving healthy cells alone. Another interesting feature of Par 4 is its ability to be suppressed and subsequently reactivated. Due to its ability to be reactivated, researchers are now trying to establish a safe and effective manner to effect reactivation of Par 4 in cancerous cells.
"If Par-4 is still present in the cells, the strategy should be to try and utilize that Par-4, so as to restore its apoptotic function and bring about apoptosis [cell death] of the cancer cells," Rangnekar said.
Do not, however, expect this new theoretical treatment to go into human clinical trials any time soon. Teams are still trying to explore both natural and synthetic agents that are able to to restore gene expression of Par 4 in human cells. The six years that have elapsed since the discovery of Par 4 have led to significant advancements in the field of cancer research. As teams continue studies involving Par 4, researchers feel they are inching closer to being able to develop treatments for and prevention of some of the deadlier forms of cancer.
Speaking on the studies taking place at his own university, Rangnekar stated, "Our multi-disciplinary team, working together, uses a multi-faceted strategy in our research. This allows us to gain a better understanding of the complexities of cancer in order to effectively kill recurrent tumor cells, especially those that have spread from their origin to distant tissue sites."