When a persistent cancerous tumor starts to grow back after chemotherapy, it is often immune to all known drugs. But a new study published in the current issue of Clinical Cancer Research indicates that a first strike with a certain class of chemicals can break this resistance. If this strategy tested in a petri dish, holds the animal and human trials, it could become one punch KO one to two for many cancers.
Tumors can become resistant to chemotherapy by activating a cellular protein called P-glycoprotein, which is considered to pump chemotherapy drugs out of the cell. Most cells are only small amounts of this protein pump, and they succumbed to the drug. But the few cells that can over-express the gene of the pump in response to the attack often survive toxic, expelling any of several drugs.
Joshua Hamilton and colleagues at Dartmouth Medical School in Hanover, New Hampshire, was the study of a class of chemotherapeutic agents that damage DNA by merging its strands, preventing the cell make proteins. In previous work, they found that some of these compounds such as mitomycin C genes which rotate in response to their environment, such as the gene for the P glycoprotein attacked. To disable the pump before any other gene toxic agent may be expelled, the researchers added mitomycin C in liver tumor cells resistant rats. After waiting 24 hours for the existing pump protein (and mRNA which helps produce them) to degrade, they added a standard chemotherapy agent called doxorubicin, which inhibits the replication of the corresponding DNA. The action of the pump has been halved, and doxorubicin has become 5 times more effective in killing resistant tumor cells.
"It is an interesting mechanism and should continue," says Martin Brown, a cancer biologist at Stanford University. Although the improvement was less marked in four other tumor cell types Hamilton noted that the case-mitomycin C pump can boost the effectiveness of several different chemotherapy regimens. "It is my belief that we should not better drugs, we need smarter ways to use the drugs we have, "he said.
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