A new two-part therapy combining a modified sugar molecule with two cancer killing drugs causes many types of cancer cells to "commit suicide" by apoptosis, a type of programmed cell death, researchers at UC San Diego and Kyushu University wrote.
Project scientist Guy Perkins, PhD of UC San Diego's Center for Research in Biological Systems and co-author senior researcher Ryuji Yamaguchi, PhD of Kyushu University Medical School in Fukuoka, Japan altered glucose or sugar molecules into a form called 2-deoxyglucose (2-DG) that cancer cells gobble readily for fuel to grow and multiply, though it cannot be used for energy and hampers growth instead, then primes a trigger for early cell death that a second drug (itself a combination of two cancer-fighting drugs) activates, ScienceDaily and New Scientist reported about the team's successful experiments with the two-phase treatment on cell cultures and animals detailed in Cancer Research.
The treatment works like a trick: Cancer cells readily take in 2-DG, but instead of providing energy for growing and multiplying the tweaked sugar molecule dislodges a protein within the cancer cells that prevents another protein from initiating apoptosis, a type of intracellular death program.
Then exposure to the combination drug ABT-263/737 signals the second protein to begin the cancer cell's self-destruct sequence.
According to the team, a wide range of cancer cells primed for death by 2-DG then exposed to ABT-263/737 are affected, but not healthy brain cells that also take in lots of sugar, because the body's blood-brain barrier stops ABT-263/737.
The 2-DG with ABT-263/737 treatment killed lung, liver, blood, cervical and breast cancer cells at multiple growth stages, and in a mouse trial the two-part treatment wiped out aggressive prostate cancer tumors in days, experiments demonstrated.
Perkins explained why this approach bypasses susceptible cancer cells' knack for resisting chemotherapy by mutating rapidly:
"Since the combination of 2-DG and ABT-263/737 induces rapid apoptosis through the intrinsic pathway, meaning through mitochondria, it leaves little room for interference by a cancer cell's highly active mutagenic programs."
But the new combined treatment does not work on all cancers, Yamaguchi explained, because some cancers are resistant or it would cause thrombopenia (platelet loss) and lymphopenia (lymphocyte loss).
Possible workarounds include storing and transplanting hematopoietic stem cells, according to the team.
The researchers are preparing for a clinical trial at UC San Diego, and Yamaguchi stated the prospects are encouraging:
"Since both 2-DG and ABT-263 (Navitoclax) are already in Phase II clinical trials (for other treatments), we know something about the safety of these agents. Once we take precautionary measures, the 2-DG-ABT combination therapy may prove an effective alternative to some existing cancer therapies. We may have found a simple, partial solution to a very complex disease."