Intrinsic and acquired drug resistance in malignant tumors. The main reason for therapeutic failure

Abstract

Drug resistance is the major reason for failure in cancer chemotherapy. Resistance may be either pre-existent (intrinsic resistance), or induced by drugs (acquired resistance), So far, no strategy has been found to overcome resistance, which is based on highly complex and individually variable biological mechanisms. In present clinical practice, drug resistance can only be recognized during treatment, after long lag times. Thus diagnostic tests are re quired, indicating resistance at an earlier stage, in order to avoid unnecessary medication, frequently associated with toxic side-effects. A number of new anti-cancer drugs are now available. In contrast to the unspecifically acting cytostatic chemotherapy, these compounds have targeted actions. However, as recent studies have shown, resistances and severe side-effects can also be found with targeted drugs. With the increasing number of new treatment regimens, the early diagnosis of resistance will optimize therapy, and indeed will be indispensable for individual cancer therapy. The resistance assays available for use in clinical practice should be integrated into cancer therapy. Research into this neglected area needs to be intensified.