Anti-cancer strategy of transitional cell carcinoma of bladder based on induction of different types of programmed cell deaths

Current treatment for advanced malignancy of the bladder cancer relies on combination chemotherapeutic agent regimens. In these patients chemotherapeutic resistance emerges in the form of an aggressive subpopulation of tumor cells even if there has been a good initial response. The majority of chemotherapeutic agents target mitotic cancer cells by inducing DNA damage pathways or altering cell cycle regulation. Drug resistance often arises from the remaining post-mitotic cancer cells, which can be further targeted by triggering the intrinsic apoptotic, autophagic, or necrotic pathways. If the death pathway could be activated extrinsically, there would be the potential for a synergistic toxic effect on tumor cells. In addition, if the death pathway was identified as being nonfunctional for any of the reasons outlined, the restoration of function could reactivate the immune system anti-tumor response. Current strategy is to decipher the complexities of death pathways in order to identify key effector molecules and their function. As their mechanisms have been elucidated, so has the knowledge that aberrations can occur at many points along the pathway, interfering with normal function. This has fueled exciting new research attempts to engineer novel therapeutic options.