Cancer therapy in good order

Abstract

Cancer Treatment of cancer patients with two or more drugs acting through different mechanisms is a strategy that has prolonged many lives. Whether the drugs within these combination therapies are delivered concurrently or sequentially can have a major impact on efficacy. A new study illustrates this principle for drugs that inhibit cell cycle kinases CDK4 and CDK6 (CDK4/6 inhibitors), which have attracted great interest because of their clinical efficacy in breast cancer. Studying mouse models of pancreatic cancer, Salvador-Barbero et al. found that sequential treatment with Taxol (which inhibits mitosis) followed by a CDK4/6 inhibitor (which prevents cell cycle entry) offered substantially more therapeutic benefit than concurrent treatment with the drugs. Mechanistically, this is because the CDK4/6 inhibitor prevents cancer cells from repairing the chromosomal damage caused by Taxol. Cancer Cell 10.1016/j.ccell.2020.01.007 (2020).