Potential anti-cancer therapy that Starves cancer cells of Glucose

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Stanford University School of Medicine researchers have found that a substance that is the achilles heel of certain cancer cells attack by robbing them of their source of energy, the sugar glucose.

Cancer chemotherapy can be a rough ride, partly because most of these drugs don't distinguish between what is cancer and what not. The chemical substances all quickly divide cells of cancer cells, blood cells and the cells that make her. Drugs that are focused on a biological phenomenon only found in cancer cells, such as the compound recently discovered by researchers at Stanford, however, could effectively combat disease with minimal side effects. The finding was published in Science Translational Medicine.

"This study shows an approach for selective inhibition of the ability of cancer cells to take up glucose, which is a pretty powerful way of killing those cells," said senior study author Amato Giaccia, PhD, Professor and Director of radiotherapy.

The researchers focused their study on the most common form of kidney cancer in adults, renal cell carcinomas, which nearly 2% of all cases of cancer in the United States, according to the Centers for Disease Control and Prevention. The disease is resistant to typical chemotherapy and patients often have that removed the affected kidney. Almost carry 90 percent of these cancers a specific genetic mutation that leads to uncontrolled cell growth.

"Most normal tissues in the body do not have this mutation, so a drug that focuses on this vulnerability very specific for cancer cells," said Giaccia, who is also a member of the Stanford Cancer Institute.

With the help of the Stanford High-Throughput Bioscience Center, the team a library of 64,000 synthetic chemical compounds on tumor cells with that mutation tested and then searched for signs of cell death.

The Panel produced two candidate cancer medicines, a reported by Giaccia in 2008, STF-62247, who is now in preclinical testing. The other, STF-31, described in the new study, kills the cancer cells in a different way, so a combination of the two drugs would allow a multiple attack. "Or, as a cancer resistant to one composite is, you have another option," said Denise Chan, PhD, former postdoctoral researcher at Stanford and co-first author of the new study.

Most renal cell carcinomas energy production through a biochemical process called aerobic glycolysis, one that usually do not require healthy cells. The energy process depends on the ability of cells to take up glucose from their environment. "The cells that we are focusing on are heavily dependent on glucose transport for the production of energy," said Chan, who is now an assistant professor at UC-San Francisco. "This compound stops the cells to transport of glucose, so that it starves them."

Renal cell carcinomas are not the only cancer cells that glucose bellies. Many cancers show up their rate of glucose import, a fact used by doctors to check cancers in living patients. Doctors may inject a radioactive-labeled glucose and follow the recording in the body with a pet scan. Using a similarly labeled glucose, took the team that STF-31 the amount of the cancer cells can ingest reduced glucose, thus robbing them of their source of energy.

The team also tested the compound in a mouse model of kidney cancer and found that STF-31 almost halved the amount of glucose introduced by tumours and slowed tumor growth. In mice, at least seems to be the drug to have few side effects. Mice treated with the compound for 14 days had no visible damage to their normal tissues: they maintain a normal immune system and the normal number of cells of the blood. "The other large tissue that comes up when you think glucose transport is the brain, and we don't see toxicity to the brain," said Chan.

Predicts further experiments showed that STF-31 directly to a carrier of glucose binds, probably block the pores of the channel-like molecule, computational modeling. The team hopes to find other types of cancer that depending on the same glucose transporter. Palo Alto biotech company Ruga Inc., co-founded by Giaccia, has license the drug for preclinical testing. Giaccia is on the company's scientific advisory board; Chan acts as a consultant.

Comments:

Former Stanford MD/PhD student Patrick Sutphin is the author of a co-first with Chan. other Stanford co-authors are former postdoctoral scholars Sandra Turcotte, PhD, Edwin Lai, PhD, and Jen Chi-Tsan, MD, PhD; current Postdoctoral Scholar Alice Banh, PhD; former master student Phuong Nguyen, MD; David Solow-Cordero, PhD, Director, and Jason Wu of Stanford's High-Throughput Bioscience Center; Veterinary pathologist Donna Bouley, DVM, PhD; and Assistant professor of radiotherapy Edward Graves, PhD. The Stanford researchers together with colleagues at Duke Medical Center in North Carolina and the University of Auckland in New Zealand.

The study was funded by action to cure kidney cancer, Cecile and Ken Youner Fund for cancer research, the Association for International cancer research, the Maurice Wilkins Centre for Biodiscovery and the National Cancer Institute.

Article reference:
Stanford University Medical Center