ICRF Research Points to Gene Manipulation as New Way to Treat Cancer
Ongoing research supported by the Israel Cancer Research Fund (ICRF) has identified a potentially new way of treating the most common form of bone cancer (osteosarcoma), lung cancer and other cancer types. A team of investigators led by Professor Doron Ginsberg of the Faculty of Life Sciences at Bar-Ilan University in Ramat-Gan, Israel, has been focusing its studies on the actions of a gene "transcription factor" (E2F1) that has been identified as a pivotal regulator of cell growth in humans.
Transcription factors are proteins that control which genes are turned on or off in the genome. They can promote or block the enzyme that controls the reading ("transcription") of genes, making the genes more or less active. Thus, they play important roles in development of cells, the sending of signals within a cell, and the entire cell cycle itself (events in a cell that lead to division and duplication). In most tumors, E2F1 becomes hyperactive, leading to abnormal cell growth -- one of the hallmarks of cancer. E2F1, however, can also activate a suicide program within cells and cause their death.
After using state of the art technologies to study the activity of tens of thousands of genes, the Israeli researchers focused on a newly-discovered group of E2F1-regulated genes (lincRNAs) believed to be important regulators in many biological processes, including cancer development.
Unlike most genes, which code for a single protein, lincRNAs code for RNA molecules that affect the level and activity of many proteins in the body. Ginsberg and his team recently demonstrated that manipulating the levels of lincRNAs in tumor cells can inhibit the cells' ability to spread and/or survive.
Using human osteosarcoma and lung cancer cells, the team showed that hyperactive E2F sensitizes to chemotherapy, and especially to the combination of doxorubicin and cisplatin, two drugs traditionally used in chemotherapy. Practically, this suggests that if E2F is introduced into tumor cells, the cells can then be treated with lower levels of chemotherapy, thus reducing the considerable toxicities associated with chemotherapy.
Thus far, three lincRNAs have been reported to be subject to E2F regulation. But the Israeli researchers say they "probably represent the tip of the iceberg" as they have identified "more than 100 lincRNAs reproducibly regulated by E2F1." Findings of their cutting-edge research were recently published in the peer-reviewed journal Molecular Cancer.
"Eventually," says Ginsberg, "such genetic manipulations may constitute a new way of treatment for cancer patients whose tumors exhibit deregulated activity of E2F1." The research could ultimately facilitate the design of cancer-treating drugs that would specifically inhibit various E2F activities.