Detall

Conventional cancer therapy consists of using drugs at a maximum tolerated dose, which in advanced disease almost invariably leads to resistance. In this lecture, I will discuss four strategies to either delay onset of resistance or even take advantage of resistance development for therapeutic benefit. As one example, I will discuss how we can use sequential drug treatment to deliver a lethal “one-two punch” to cancer cells. In this scenario, we use
the first drug to expose a major new vulnerability of the cancer cells that is subsequently targeted by the second drug. This has the advantage that the drugs do not have to be given at the same time, which allows combination of a much broader range of cancer drugs, as co-administration of drugs may be limited by toxicities. Examples of effective sequential drug treatments based on the induction of senescence in cancer followed by selective killing of senescent cells will be presented.