Neil Fleshner

MD, MPH, FRCSC

Phone

(416) 946-4501 ext. 2899

Assistant(s)

Biography

Dr. Neil Fleshner is Chair and Professor at the Division of Urology, University of Toronto. Dr. Fleshner is certified in both urology and epidemiology. He earned his MPH degree from the School of Public Health at Columbia University and completed his oncology training at Memorial Sloan Kettering Cancer Center.

Dr. Fleshner is an avid music lover and father of three.

Areas of Specialty and Research Interests

Aside from surgical practice, Dr. Fleshner conducts research on urologic cancer prevention with an emphasis on prostate cancer. He has authored over 400 scientific papers. Dr. Fleshner's current research projects include 2 randomized trials of nutritional intervention in prostate cancer as well as laboratory work assessing oxidative biomarkers and cell cycle regulation in prostate cancer cells exposed to micronutrients.

Affiliated Hospital(s)

Mount Sinai Hospital, Princess Margaret Cancer Centre (UHN), Toronto General Hospital (UHN)
 
 

Latest Publications

Targeting MCT4 to reduce lactic acid secretion and glycolysis for treatment of neuroendocrine prostate cancer.

Related Articles

Targeting MCT4 to reduce lactic acid secretion and glycolysis for treatment of neuroendocrine prostate cancer.

Cancer Med. 2018 Jun 14;:

Authors: Choi SYC, Ettinger SL, Lin D, Xue H, Ci X, Nabavi N, Bell RH, Mo F, Gout PW, Fleshner NE, Gleave ME, Collins CC, Wang Y

Abstract
Development of neuroendocrine prostate cancer (NEPC) is emerging as a major problem in clinical management of advanced prostate cancer (PCa). As increasingly potent androgen receptor (AR)-targeting antiandrogens are more widely used, PCa transdifferentiation into AR-independent NEPC as a mechanism of treatment resistance becomes more common and precarious, since NEPC is a lethal PCa subtype urgently requiring effective therapy. Reprogrammed glucose metabolism of cancers, that is elevated aerobic glycolysis involving increased lactic acid production/secretion, plays a key role in multiple cancer-promoting processes and has been implicated in therapeutics development. Here, we examined NEPC glucose metabolism using our unique panel of patient-derived xenograft PCa models and patient tumors. By calculating metabolic pathway scores using gene expression data, we found that elevated glycolysis coupled to increased lactic acid production/secretion is an important metabolic feature of NEPC. Specific inhibition of expression of MCT4 (a plasma membrane lactic acid transporter) by antisense oligonucleotides led to reduced lactic acid secretion as well as reduced glucose metabolism and NEPC cell proliferation. Taken together, our results indicate that elevated glycolysis coupled to excessive MCT4-mediated lactic acid secretion is clinically relevant and functionally important to NEPC. Inhibition of MCT4 expression appears to be a promising therapeutic strategy for NEPC.

PMID: 29905005 [PubMed - as supplied by publisher]