Gene therapy for carcinoma of the breast - Pro-apoptotic gene therapy

The dysregulation of apoptosis contributes in a variety of ways to the mali gnant phenotype. It is increasingly recognized that the alteration of pro-a poptotic and anti-apoptotic molecules determines not only escape from mecha nisms that control cell cycle and DNA damage, but also endows the cancer ce lls with the capacity to survive in the presence of a metabolically adverse milieu, to resist the attack of the immune system, to locally invade and s urvive despite a lack of tissue anchorage, and to evade the otherwise letha l insults induced by drugs and radiotherapy. A multitude of apoptosis media tors has been identified in the past decade, and the roles of several of th em in breast cancer have been delineated by studying the clinical correlate s of pathologically documented abnormalities. Using this information, attem pts are being made to correct the fundamental anomalies at the genetic leve l. Fundamental to this end are the design of more efficient and selective g ene transfer systems, and the employment of complex interventions that are tailored to breast cancer and that are aimed concomitantly towards differen t components of the redundant regulatory pathways. The combination of such genetic modifications is most likely to be effective when combined with con ventional treatments, thus robustly activating several pro-apoptotic pathwa ys.