Determining how a sugar molecule can affect cancer cell response to chemoradiotherapy gumedcenter nchembio
to reprogram their metabolism has been key to jumpstarting this latest research effort in the hope that we can gain a better understanding of how we can fight cancer at the cellular, or even subcellular level."
Pei's current research effort started when he and his colleagues looked at how nutrients that cells gobble up to stay alive end up triggering modifications to proteins as a result of adding a sugar called O-linked β-N-acetylglucosamine to the protein. This dynamic and reversible modification is emerging as a key regulator of a number of different cellular processes.
In a series of experiments in both the lab and in mice, the researchers were able to determine that there is an important enzyme involved in nucleotide synthesis, called phosphoribosyl pyrophosphate synthetase 1 , that is modified by O-G1cNAc. Targeting either the sugar or the enzyme could be key to affecting cancer outcomes, the researchers believe.
"Ultimately, we would like to be able to design drugs that target DNA nucleotide synthesis, which includes the modifications we've identified of adding a sugar to a protein and the catalyzing step acted on by the PRPS1 enzyme," said Pei."In particular, we'd like to develop drugs that can be used to makemore sensitive, or responsive, to radiotherapy and chemotherapy, as resistance to these therapies is still far too common.
Meanwhile, the researchers next step is to start examining applications of their findings in animal models by using mice grafted with human lung cancer tissue to see if drugs targeting nucleotide synthesis sensitize lung
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