Advanced cancers: eradication in all cases using 3-bromopyruvate therapy to deplete ATP.
A common feature of many advanced cancers is their enhanced capacity to metabolize glucose to lactic acid. In a challenging study designed to assess whether such cancers can be debilitated, we seeded hepatocellular carcinoma cells expressing the highly glycolytic phenotype into two different locations of young rats. Advanced cancers (2-3cm) developed and were treated with the alkylating agent 3-bromopyruvate, a lactate/pyruvate analog shown here to selectively deplete ATP and induce cell death. In all 19 treated animals advanced cancers were eradicated without apparent toxicity or recurrence. These findings attest to the feasibility of completely destroying advanced, highly glycolytic cancers.
Ko
Young H
YH
The Russell H. Morgan Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2185, USA. yko@jhmi.edu <yko@jhmi.edu>
Smith
Barbara L
BL
Wang
Yuchuan
Y
Pomper
Martin G
MG
Rini
David A
DA
Torbenson
Michael S
MS
Hullihen
Joanne
J
Pedersen
Peter L
PL
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000378:metabolism* / Q000627:therapeutic use*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009368:Neoplasm Transplantation; D011773:Pyruvates / Q000378:metabolism* / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015996:Survival Rate
D004791:Enzyme Inhibitors; D011773:Pyruvates; C017092:bromopyruvate; D000255:Adenosine Triphosphate; D005947:Glucose