Prostate Cancer and Neuroendocrine Differentiation: More Neuronal, Less Endocrine?

Regional anesthesia is known to prevent or attenuate the surgical stress response; therefore, inhibiting surgical stress by paravertebral anesthesia might attenuate perioperative factors that enhance tumor growth and spread. The authors hypothesized that breast cancer patients undergoing surgery with paravertebral anesthesia and analgesia combined with general anesthesia have a lower incidence of cancer recurrence or metastases than patients undergoing surgery with general anesthesia and patient-controlled morphine analgesia. In this retrospective study, the authors examined the medical records of 129 consecutive patients undergoing mastectomy and axillary clearance for breast cancer between September 2001 and December 2002. Fifty patients had surgery with paravertebral anesthesia and analgesia combined with general anesthesia, and 79 patients had general anesthesia combined with postoperative morphine analgesia. The follow-up time was 32 +/- 5 months (mean +/- SD). There were no significant differences in patients or surgical details, tumor presentation, or prognostic factors. Recurrence- and metastasis-free survival was 94% (95% confidence interval, 87-100%) and 82% (74-91%) at 24 months and 94% (87-100%) and 77% (68-87%) at 36 months in the paravertebral and general anesthesia patients, respectively (P = 0.012). This retrospective analysis suggests that paravertebral anesthesia and analgesia for breast cancer surgery reduces the risk of recurrence or metastasis during the initial years of follow-up. Prospective trials evaluating the effects of regional analgesia and morphine sparing on cancer recurrence seem warranted.

Selective targeting of cancer stem cells (CSCs) offers promise for a new generation of therapeutics. However, assays for both human CSCs and normal stem cells that are amenable to robust biological screens are limited. Using a discovery platform that reveals differences between neoplastic and normal human pluripotent stem cells (hPSC), we identify small molecules from libraries of known compounds that induce differentiation to overcome neoplastic self-renewal. Surprisingly, thioridazine, an antipsychotic drug, selectively targets the neoplastic cells, and impairs human somatic CSCs capable of in vivo leukemic disease initiation while having no effect on normal blood SCs. The drug antagonizes dopamine receptors that are expressed on CSCs and on breast cancer cells as well. These results suggest that dopamine receptors may serve as a biomarker for diverse malignancies, demonstrate the utility of using neoplastic hPSCs for identifying CSC-targeting drugs, and provide support for the use of differentiation as a therapeutic strategy. Copyright © 2012 Elsevier Inc. All rights reserved.