An update in neoadjuvant chemotherapy in cervical cancer.

More than two decades have passed since neoadjuvant chemotherapy has been introduced in the clinical practice. After several pilot studies, randomized trials and meta-analysis have confirmed the validity of this therapeutic strategy and in particular of neoadjuvant chemotherapy followed by radical surgery. Several open questions still remain unanswered and in particular no standard drug regiment is unanimously accepted. In this paper we describe how this treatment has evolved since its original introduction in the early eighties and describe possible drug regimens with their supporting evidence that can be adopted by physicians worldwide.

A small molecule Smac mimic potentiates TRAIL-mediated cell death of ovarian cancer cells.

OBJECTIVES: Ovarian cancer remains a leading cause of death in women and development of new therapies is essential. Second mitochondria derived activator of caspase (Smac) has been described to sensitize for apoptosis. We have explored the proapoptotic activity of a small molecule mimic of Smac/DIABLO on ovarian cancer cell lines (A2780 cells and its chemoresistant derivatives A2780/ADR and A2780/DDP), cancer cell lines and in primary ovarian cancer cells. METHODS: The effects of a small molecule mimic of Smac/DIABLO on ovarian cancer cell lines and primary ovarian cancer cells were determined by cell proliferation, apoptosis and biochemical assays. RESULTS: This compound added alone elicited only a weak proapoptotic effect; however, it strongly synergizes with tumor necrosis factor-related apoptosis inducing ligand (TRAIL) or agonistic TRAILR2 antibody (Lexatumumab) in inducing apoptosis of ovarian cancer cells. CONCLUSIONS: These observations suggest that small molecule mimic of Smac/DIABLO could be useful for the development of experimental strategies aiming to treat ovarian cancer. Interestingly, in addition to its well known proapoptotic effects, Smac/DIABLO elicited a significant increase of pro-caspase-3 levels.