Scientists have made a breakthrough in oncology by finding a way to modify lung cancer cells to make them more vulnerable to treatment, overcoming drug resistance. This new approach involves editing cancer cells with two new “switches” that enable them to outgrow the rest of the cancer cell population and unleash a toxic drug onto the remaining tumor cells.
In a proof-of-concept study published in the journal Nature Biotechnology, researchers inserted two “suicide genes” into cancer cells in lab dishes. One gene controls the activation of a protein called epidermal growth factor receptor (EGFR) with the help of a cancer drug called erlotinib. By reversing the drug’s usual action, the modified cells become resistant to the drug on purpose, allowing researchers to switch the cells’ proliferation on and off.
This approach was tested on non-small cell lung cancer (NSCLC) cells, which commonly develop resistance to erlotinib after about a year of treatment. The modified cells easily outgrew the unmodified cells, and when a harmless molecule called 5-FC was introduced to activate the second suicide gene, the cells transformed it into a toxin that killed both the modified cancer cells and the surrounding cells.
While this dual-switch selection gene drive approach is innovative, it does not address resistance generally, according to cancer pharmacologist Aaron Goldman. However, combining this approach with a therapy that prevents the development of resistance could be a promising strategy for future cancer treatments.
The researchers are now testing this dual-switch approach with other cancers and therapies, with the goal of developing a generalizable platform for delivering therapeutic genes in cancer. This technology has the potential to create new therapeutic opportunities that may lead to cures in the future.
