Researchers discover how arginine hunger specifically kills cancer cells -
Researchers at UC Davis, City of Hope Medical University Taipai and national health research institutes Taiwan have discovered how a drug that deprives cells of an essential amino acid specifically kills cancer cells.
Their paper, published today in Proceedings of the National Academy of Sciences , is the culmination of nearly a decade of research on the role of arginine - and his deprivation -. in the generation of excessive autophagy, a process in which the cell dies by himself eating
Study coauthor Hsing-Jien Kung, a renowned cancer biologist and UC Davis professor emeritus who heads now the national health research Institutes in Taipei, Taiwan, first discovered the mechanism by which arginine deprivation works in 09, when he led fundamental scientific research at UC Davis Cancer Center complete.
"traditional cancer therapies involving" poisoning "by toxic chemicals or" burns "by cancer cells to radiation death, which often have side effects," said Kung. "A new strategy is to "starve" cancer cells to death, taking advantage of different metabolic requirements of normal and cancer cells. This approach is generally milder, but this study shows, it also uses a different mechanism of death, which can complement the destructive effects of conventional therapy. "
The discovery led to the further development of a drug being tested in several clinical trials against melanoma, prostate, liver, sarcoma and other cancers that lack of an enzyme that helps synthesize arginine, an amino acid with an essential role in cell division, immune function and hormone regulation.
the study published today describes how arginine famine specifically kills cells tumor with a new mechanism involving mitochondrial dysfunction, production of reactive oxygen species, nuclear DNA leakage and autophagy chromatin, DNA where leakage is captured and "consumed" by giant autophagosomes.
Contrary to apoptosis, a process of cell death wherein the DNA is damaged inside the cell nucleus, chromatin autophagy in the nucleus is fragmented and its parts the shuttle out of the lysosome (an organelle within the cell membrane) where the fragments are degraded.
"It has long been recognized that some cancer cells are resistant to apoptosis," said Richard Bold, professor and chief of surgical oncology at UC Davis Comprehensive Cancer and a co-author of the study. "Now we have another way to induce cells to undergo death overcomes resistance to traditional apoptosis associated with cancer."
the authors suggest that the use of arginine -privation induced autophagy may also spare patients the toxicity associated with chemotherapy alone.
drug examined in the study is ADI-PEG20, developed by Polaris Pharmaceuticals of San Diego. ADI-PEG20 is an enzyme that degrades arginine, which would normally be available to the cell, breaking it down into its precursors. the agent is currently in phase III clinical trials in liver cancer, stage II melanoma and phase I in cancer prostate.
Primo Lara, UC Davis oncologist and associate director of translational research at Cancer Center, led a phase I study of the drug in patients with advanced lung, prostate and oral cancers. He reported that combined with a chemotherapy agent, the drug was feasible and reasonably tolerated. It is currently recruiting prostate cancer patients advanced for a new Phase I trial of the combination of drugs.
"This opens a new field," said Bold. "Now we are seeking other agents that use this method and translate these clinical trials."
EmoticonEmoticon