When biochemist Susan Band Horwitz started studying Taxol, there wasn’t much interest in it. It’s a naturally occurring molecule from the yew tree, and Horwitz saw potential in its unique structure. Her work turned it into one of the most important chemotherapy drugs in the clinic, prescribed to millions of cancer patients worldwide.
Horwitz, distinguished professor of molecular pharmacology at the Albert Einstein College of Medicine, was recognized with the 2019 Canada Gairdner International Award for this groundbreaking research.
“I started looking at Taxol in the 1970s,” says Horwitz. “It is an amazing structure, just amazing. It’s very hydrophobic; that means that it’s a drug that doesn’t dissolve very well in water. And the structure is extraordinarily complex, very architecturally complex. So it has always been a problem as to how to give this drug to patients.”
Despite the challenges, Horwitz demonstrated that Taxol worked like no other drug ever described. She determined that Taxol could bind structural filaments in the cell called microtubules and stabilize them, preventing them from carrying out their normal activities, and that’s what helped bring it to the market.
“Microtubules are part of the cytoskeleton of a cell, and they have to be dynamic,” explains Horwitz. “That’s their normal process because they pull the DNA apart so that each daughter cell gets an equal amount of DNA when a cell is going to divide.”
But Taxol made this impossible by binding to the subunits of microtubules, a protein called tubulin. When that happens, the microtubules can’t disassemble. This stability locks cells in the part of the cell cycle right before cell division, triggering programmed cell death. That’s what makes it so useful for killing cancer cells, and it has now been prescribed to millions of people, in particular women who have ovarian and breast cancer.
“I’m thrilled by so many people who can say, I’m alive partly because of Taxol,” says Horwitz. “It’s an incredibly gratifying experience.”
