Resistance to cancer drugs continues to be a major impediment in medical oncology, and can limit the effectiveness of modern cancer treatments. Drug resistance can develop after months or years of effective treatment. However, understanding the changes that make cancer cells resistant to a drug can help scientists develop a next-generation therapy.
Researchers at the University of California in San Francisco, and Memorial Sloan Kettering Cancer Center in New York are trying to get ahead of the resistance problem by considering third-generation mTOR inhibitors without waiting for resistance to the latest therapies to develop. They have developed a potential cancer therapy with a unique strategy to block the mTOR molecule.
mTOR helps to drive the growth of many tumours. Rapamycin is the oldest of the drugs that block mTOR, and it has had success in treating a few types of cancer, including kidney and breast cancers. Clinical trials evaluating second-generation mTOR inhibitors, rapalogs, which are more potent than the first-generation molecules, are currently ongoing.
The researchers mimicked antibodies by creating an inhibitor that binds mTOR in 2 places. The new mTOR inhibitor, Rapalink, links a first-generation mTOR inhibitor, which binds to one part of the mTOR molecule, to a second-generation mTOR inhibitor, which binds to a different part of the mTOR molecule nearby. In animal experiments, Rapalink reduced the size of tumours that were resistant to earlier-generation mTOR inhibitors.