A team of researchers has found that a novel combination of a specific sugar molecule with a pair of cell-killing drugs prompts a wide variety of cancer cell types to kill themselves, a process called apoptosis or programmed cell death.
“The goal of targeted therapy is to stop the growth of cancerous cells while doing little or no harm to healthy tissue,” said Guy Perkins, PhD, associate project scientist at the Centre for Research in Biological Systems at UC San Diego.
The new two-part therapy described by Perkins and co-author Ryuji Yamaguchi, PhD, senior researcher at Kyushu University Medical School in Fukuoka, Japan, focuses on depriving cancer cells of their fundamental need for sugar to fuel growth and multiplication.
The first component is a modified glucose or sugar molecule called 2-deoxyglucose (2-DG).
Although readily taken in by sugar-hungry cancer cells, it cannot be broken down to produce energy. Instead, it hampers cancer cell growth and primes the cells for early death by opening access to an internal protein that can trigger apoptosis.
Cells primed with 2-DG are then exposed to a pair of drugs, ABT-263/737, which signal the internal protein to initiate cell death. The researchers say only cancer cells sensitised for death by 2-DG and exposed to ABT-263/737 are broadly impacted.
Healthy brain cells, which are also highly glycolytic like cancer cells, are protected because ABT-263/737 cannot cross the body’s blood-brain barrier.
After first determining that in vitro cancer cells incubated with 2-DG and exposed to low concentrations of ABT-263/737 died, the researchers conducted animal studies.
They found that when 2-DG was injected into animals, it predominantly accumulated in cancer cells that were subsequently killed by an injection of ABT-263/737.
The two-step approach successfully induced apoptosis in leukemia, hepatocarcinoma, lung, breast and cervical cancers.
Yamaguchi said it caused cell death at many stages of cancer development, including a difficult-to-treat, chemo-resistant, highly metastasized form of prostate cancer.
The findings are reported online in the journal Cancer Research.