In the nucleus of every cell, DNA is twisted into a double helix, but sometimes it forms loops and knots. One such knot is the G-quadruplex: four DNA strands fold into a square stack, like cards in a deck. Tumor cells have more of these knots than healthy ones because their DNA is constantly rearranging. If you jam these knots, the cell can't copy its genes and dies.
Scientists took seven testicular cancer cell lines and two healthy cell lines and treated them with various compounds that bind to G-quadruplexes. CX-5461 proved the most selective: it killed cancer cells at concentrations 10-160 times lower than those needed to affect healthy cells. Under the microscope, DNA damage accumulated in the cancer cells while healthy ones remained intact.
Further analysis showed that CX-5461 sets off a chain of events: the DNA knots get jammed, the cell stops reading important genes, accumulates damage, and switches on its self-destruct program. In healthy cells, however, there are few knots, so the drug barely touches them. It's like a key that jams the lock only in the doors of tumor cells, leaving the doors of healthy cells open.
Today CX-5461 is already being tested against other tumors. New data suggest it could also help in testicular cancer, especially for those who didn't respond to cisplatin. The next step is to see whether it can be combined with existing drugs to treat resistant tumors without severe side effects. The key to the lock has been found; now we just need to find the right combination.
G-quadruplexes are four-stranded DNA structures that form in guanine-rich regions. They resemble stacked square plates and can block the work of enzymes that copy DNA.
Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.