ABSTRACT

One of the major unsolved problems in cancer treatment is drug resistance at the time of initial chemotherapy (innate drug resistance) or following an initial period of clinical response to the chemotherapeutic drugs (acquired drug resistance). With the advances in cell and molecular biology, our understanding of the mechanisms involved in drug resistance has broadened considerably. Among the mechanisms used by tumor cells that become resistant to various types of drug treatments are those effective not only against cytotoxic drugs but also to other forms of therapies-e.g., radiotherapies, hormonotherapies, thermotherapies, and gene therapies. This is seen when complex mechanisms regulated through several different pathways are involved, as occurs with those interfering with apoptosis. The heat shock protein (HSP)-regulated mechanisms are also very complex, and it is reasonable to expect that they could be involved with resistance to several forms of cancer treatment. HSPs are synthesized by stressed cells; the list of stressors is very large, and in general the response is useful in defending the cells against the noxa( e) that induced the stress protein response: these proteins participate in the homeostasis of the cell by performing a multiplicity of functions.