New CALTECH Research Provides Framework for Improving Cancer Diagnosis and Treatment.
A team of researchers at the California Institute of Technology have designed a new approach to killing cancer cells by using ‘programmed’ RNA molecules.
The process, developed by Niles Pierce uses small RNA molecules that can be programmed to attack only specific cancer cells; then, by changing shape, those molecules cause the cancer cells to self-destruct.
It’s common knowledge that chemotherapy patients experience debilitating effects as a result from the cancer drugs that they are prescribed. These medicines attack not only the cancer cells, but unfortunately also normal, healthy cells. According to Pierce, its better to create drugs that can make the distinction between cancer cells and healthy cells and then once identified, wipe them out completely. In other words, produce molecules that diagnose cancer cells before destroying them. Not only could this type of therapy do away with the side effects associated with conventional chemotherapy treatments, it could also be tailored on a molecular level to individual cancers, making it uniquely specific.
The new process involves the use of two different varieties of small conditional RNA and ‘tricking’ cancer cells into self-destruction by selectively forming long double-stranded RNA polymers that mimic viral RNA. As part of a typical antiviral immune response, human cells defend against infection using a protein called protein kinase R (PKR): to search for long double-stranded viral RNA, which should not be present in healthy human cells. If PKR indeed detects long double-stranded RNA within a cell, the protein triggers a cell-death pathway to actually eliminate the cell!
Current testing by Pierce and his team involve lab-grown human cells derived from three types of cancers: glioblastoma, prostate carcinoma, and Ewing’s sarcoma (a type of bone tumor). Pierce says: “We used three different pairs of small conditional RNAs,” with each pair designed to recognize a marker found in one of the three types of cancer, he explains. “The molecules caused a 20- to 100-fold drop in the numbers of cancer cells containing the targeted RNA cancer markers, but no measurable reduction in cells lacking the markers.” For example, he explains, “drug 1 killed cancer 1 but not cancers 2 and 3, while drug 2 killed cancer 2 but not cancers 1 and 3, and drug 3 killed cancer 3 but not cancers 1 and 2.”
“Conceptually,” Pierce says, “small conditional RNAs provide a versatile framework for diagnosing and treating disease one cell at a time within the human body. However,” he notes, “many years of work remain to establish whether the conceptual promise of small conditional RNAs can be realized in human patients.”
The work was funded by the National Cancer Institute, the Elsa U. Pardee Foundation, the National Science Foundation’s Molecular Programming Project, the Caltech Center for Biological Circuit Design, the Caltech Innovation Initiative, the Beckman Institute at Caltech, and a Caltech grubstake fund.
Ream more about selective cell death mediated by small conditional RNAs