Scientists therapeutic system engineer with both arms for a better fit on the target cancer -
Scientists have designed a kind of biological barbell that can get inside cancer cells and cause damage to two proteins that work independently and together to ensure the survival and spread of cancer.
Their therapeutic strategy comprises a molecule at each end called an aptamer that targets, in this case prostate cancer. Interposed between the two smaller molecules, called siRNA, which, once delivered to the interior of the cell, can destroy RNA messenger making these proteins.
This new combination of aptamer at each end between two siRNAs also provides a new model for more effective therapies, less toxic gene for a wide range of cancers, such as lung and breast cancer, which are common, complex, and often deadly, said the research team at the medical College of Georgia and Georgia cancer Center at the University Augusta.
"With two missiles, connecting the power is increased," said Dr Hong Yan Liu, immunologist, biochemist and biomedical engineer at the MCG Center for Biotechnology and Genomic Medicine. "It is also a way to get more and siRNA inside the cell," said corresponding author of the study in the journal Scientific Reports
Giving therapeutic system both arms -. As the antibodies the body makes to defend against the invaders - certainly gives it a better grip on its cancer target, said Dr. Jin-Xiong She, director of the Center for Biotechnology and Genomic Medicine and Georgia Research Alliance Eminent Scholar in genomic medicine
.Liu used a three-dimensional aptamer targeting specific membrane antigen of the prostate or PSMA, which is overexpressed on the surface and inside of prostate cancer cells, to help siRNA find and enter cancer cells.
"We then target two tumor-dependent genes," said Liu. She speaks of epidermal growth factor receptor, or EGFR gene and survivin to its name - because it prevents cells from committing suicide. Overexpression of EGFR is associated with prostate cancer resistant to current treatment strategies and prone to spread to the bone. Survivin overexpression is also associated with resistance to therapy, recurrence and the spread of the disease.
While both operate independently, they can also partner, sharing several signaling pathways. Indeed, when the EGFR inhibitors have been previously used, tumors can switch to the path of survivin for survival.
But the simultaneous attacks by both scientists translated by suppressing the growth of cancer and blood vessels necessary for survival in models where cancer cells from human prostate were placed into immunodeficient mice human cells were treated in a dish. Their facial expressions models of mid to late stage cancers of the prostate, which is when the most common cancer in American men and is diagnosed when many existing therapies do not work.
Small interfering RNAs or siRNAs, used to EGFR interruption and support of prostate cancer survivin have potential for cancer targets "undruggable" and there are many of them, has said Dr. Wu Daqing, study co-author and biologist cancer cancer Center in Georgia and the MCG Department of biochemistry and molecular Biology.
many of these cancer promoters hide inside cells where many drugs can not reach. Receptors on the surface of cells, including EGFR, are considered "druggable," said Wu. Always drugs already used monoclonal antibodies usually bind to the outside of the membrane receptors, and while they are specific , they can not penetrate inside the cell where proteins such as survivin are also found, Wu said. small molecule drugs can penetrate inside the cells, but generally lack specificity, which reduces increases their effectiveness and side effects. "This type of delivery system is more convenient for targeting undruggable targets," said Wu.
Cancer requires certain proteins to survive and proliferate, which are generally different from healthy cells or, at least, have much higher levels. "With this approach, you can specifically target proteins that cancer cells are addicted to," she said.
DNA or RNA based therapies stop or reduce excessive production of these proteins more often by blocking or reducing the gene expression or the production of mRNA that ultimately makes proteins.
"When you stop the production of proteins, cancer cells divide and die" she says. Like other approaches, it is not perfect since, for example, synthetically produced siRNA can degrade quickly and needs clear directions to find the target messenger RNA in cancer cells.
The next steps, which are ongoing, include the identification of missiles and target proteins for other cancers and for prostate cancer as well. Cancers, especially at an advanced stage, become more heterogeneous, meaning they use several ways to survive and thrive, which is why the most common treatments are combinations of drugs and targets. Pathways and proteins can even vary from one patient to another with the same type of cancer, to find multiple proteins for targeting improves efficiency, Wu said.
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