Mechanisms of resistance to therapy and tumor cell survival

The failure to cure patients with cancer continues to be primarily because of the development of treatment resistance. Both normal and malignant cells die by either programmed cell death (apoptosis) or by cytolysis. Malignant cells have developed mechanisms of resistance that prevent them from entering the programmed cell death pathway as well as mechanisms of escaping immune recognition and cytolysis. These mechanisms include specific protective adaptations involving drug transport, metabolism, and target interactions. Malignant cells may also become resistant to therapy through alterations in genes encoding proteins involved in the initiation of apoptotic pathways. Finally, tumor cells may develop mechanisms to escape immune recognition, making them resistant to T-cell destruction. This article provides an overview of these mechanisms, with emphasis on published articles reported within the past year.